Bridging research and practice: a systematic review of Academic entrepreneurship in healthcare and its emerging research agenda

Abstract

The global healthcare system is confronting significant structural challenges and urgently requires innovative solutions. Academic entrepreneurship has emerged as a critical response by translating medical discoveries into practical solutions. While research on academic entrepreneurship in healthcare is rapidly growing, the existing literature remains fragmented and lacks a comprehensive synthesis of its progress and future directions. This review addresses this gap by conducting a framework-based systematic literature review of 85 peer-reviewed articles sourced from Scopus and Web of Science. Guided by the SPAR-4-SLR protocol, the review employs two organizing frameworks. The antecedents-phenomenon-consequences (APC) framework uncovers the enabling and constraining factors,diverse entrepreneurial pathways, and both the positive and negative effects associated with academic entrepreneurship in healthcare. Complementing this, the theory-context-method (TCM) framework provides structured insights into the theoretical foundations, research contexts, and methodological strategies applied in the field. Additionally, the review identifies the major gaps in the existing literature and offers a few recommendations for future investigation on academic entrepreneurship in healthcare across three key dimensions: new theoretical perspectives, expanded research settings, and diversified methodological approaches. By integrating these perspectives, the study offers a synthesized understanding of existing research, identifies critical knowledge gaps, and provides actionable insights for scholars, institutional leaders, and policy stakeholders committed to advancing academic entrepreneurship in healthcare.

Introduction

Currently, the global healthcare system faces substantial structural challenges. The gap between the demand for and supply of medical services has been further exacerbated by the increasing prevalence of chronic diseases and the aging population. Simultaneously, the rising healthcare expenditures threaten the sustainability of healthcare systems. Additionally, recent public health emergencies, like the COVID-19 pandemic, have exposed critical vulnerabilities in conventional healthcare delivery systems. In light of these challenges, there is an urgent need for healthcare innovation and entrepreneurship to enable more effective, adaptive, and sustainable service delivery models [1–3].

Against this backdrop, academic entrepreneurship, as a critical channel for transferring knowledge and innovation from academia to the outside world [4, 5], is playing an increasingly significant role in facilitating the translation of medical research into healthcare solutions [6, 7]. For example, academia contributes to the development of new pharmaceuticals, medical technologies, and healthcare products via channels including spin-off enterprises, patent licensing, and technology transfer [8–10]. Moreover, academic entrepreneurship has also made a substantial contribution to the response to the COVID-19 pandemic [11, 12].

Previous research has systematically investigated academic entrepreneurship and healthcare entrepreneurship from various perspectives. For example, several studies have conducted systematic reviews of academic entrepreneurial ecosystems [4, 13], academic entrepreneurship indicators [14], and determinants underlying academic entrepreneurial intentions [15]. While these reviews provide a valuable foundation for understanding academic entrepreneurship, their broad scope often limits their ability to meaningfully capture the distinctive features of academic entrepreneurship in healthcare. More specifically, several scholars have also examined entrepreneurship within healthcare settings from various perspectives [2, 16, 17]. However, academic entrepreneurship represents a distinct phenomenon that centers on the role of the academic community in transferring and commercializing research findings, involving unique mechanisms and motivations rooted in academic institutions. Therefore, given the scarcity of systematic reviews on academic entrepreneurship in healthcare, this study contends that now is a timely and necessary juncture to consolidate existing knowledge in the field. Such an endeavor is crucial for informing and guiding future research.

Currently, the concept of academic entrepreneurship is interpreted variably across the literature. Some scholars, adopting a broad definition, argue that activities such as contract research and industry consulting should also be considered forms of academic entrepreneurship [18, 19]. In contrast, other researchers adopt a more restricted perspective, characterizing academic entrepreneurship as entrepreneurial endeavours that arise within academia and are distinctly market-orientated and risk-bearing [13, 20, 21]. To ensure conceptual clarity and analytical focus, this study adopts a relatively narrow definition of academic entrepreneurship in the healthcare context. Specifically, academic entrepreneurship in healthcare is defined as: the process by which universities, hospitals, and research institutions—or their affiliated researchers—commercialize medical research outcomes through the creation of spin-off ventures or the implementation of market-oriented patent and technology licensing, thereby generating economic and societal value. Therefore, activities such as contract research, consulting services, and university–industry collaborations are not included within the scope of this study. This narrow conceptual definition also guides the formulation of our literature search strategy: we prioritize search terms directly related to academic entrepreneurship and its core commercialization forms, to maintain the consistency of the sample boundary and avoid the inclusion of literature that deviates from the core research focus.

Despite increasing studies on academic entrepreneurship in healthcare, critical knowledge gaps remain. First, existing reviews mainly focus on general academic entrepreneurship rather than the unique context of healthcare. Second, prior research insufficiently explains how healthcare-specific institutional, clinical, regulatory, and public value logics shape the antecedents, pathways, and consequences of academic entrepreneurship. Third, few studies translate findings into practical and actionable guidance for policymakers, hospital administrators, and healthcare innovators, leaving a disconnection between research and practice. This review aims to fill these gaps, provide an integrated framework, and bridge academic research with real-world practice in academic entrepreneurship in healthcare.

Given the understanding of the distinct characteristics of academic entrepreneurship in healthcare remains limited, this study adopts a Systematic Literature Review (SLR) approach, guided by the Scientific Procedures and Rationales for Systematic Literature Reviews (SPAR-4-SLR) protocol to systematically review and synthesize existing research on academic entrepreneurship in healthcare and to propose pragmatic directions for advancing future inquiry in this field [22]. In doing so, this study aims to answer the following three research questions (RQs):

RQ1: What do we know about academic entrepreneurship in healthcare?

RQ2: How do we know about academic entrepreneurship in healthcare?

RQ3: Where should research go with academic entrepreneurship in healthcare?

The subsequent sections of this paper are structured as follows. Section 2 presents the review methodology. Section 3 addresses the RQ1—“What do we know about academic entrepreneurship in healthcare?”. Section 4 addresses the RQ2—“How do we know about academic entrepreneurship in healthcare?”. Section 5 addresses the RQ3 “where should research go with academic entrepreneurship in healthcare?”. Section 6.3.1 closes the paper with conclusion.

Methodology

The Systematic Literature Review (SLR) is widely recognized as a scientifically rigorous approach. SLRs not only help to integrate previous studies and reduce bias, but also help to uncover knowledge gaps and build a strong basis for future research [22, 23]. Systematic reviews may take different forms, such as domain-based, theory-based, and method-based reviews [24]. To answer the proposed research questions, this study adopts a domain-based review guided by two structured frameworks, namely, the TCM framework [25] and the APC framework [26, 27]. Additionally, the SPAR-4-SLR protocol [22] is employed to ensure the transparency and reproducibility of the literature review process. Figure 1 illustrates the SPAR-4-SLR protocol employed in this study, and Fig. 2 shows the research framework linking the APC and TCM frameworks.

Fig. 1.

The SPAR-4-SLR protocol adapted from [22]

Fig. 2.

The research framework linking APC and TCM framework

Review protocol

The SPAR-4-SLR protocol is a structured review framework comprising three sequential stages and six corresponding sub-stages: (i) Assembling, which involves the identification and acquisition; (ii) Arranging, which focuses on the purification and organization; and (iii) Assessing, which entails the evaluation and reporting of key findings derived from the reviewed literature [22].

Assembling

The Assembling stage consists of two sub-stages: identification and acquisition. The identification involves defining the review domain, formulating research questions, and specifying the types of documents and sources to be included.

This study focuses on academic entrepreneurship in healthcare and addresses the following research questions:

• (i)What do we know about academic entrepreneurship in healthcare?
• (ii)How do we know about academic entrepreneurship in healthcare?
• (iii)Where should research go with academic entrepreneurship in healthcare?

This review includes only research articles from peer-reviewed journals, excluding books, dissertations, reports, and other publications that lack rigorous peer review [22]. Source quality was ensured by including only research articles indexed in Scopus and the Web of Science (WoS). These two databases were selected as our sole data sources for two core reasons: first, they are the most widely used and authoritative databases for systematic literature reviews in the cross-cutting fields of entrepreneurship research, innovation research, and healthcare research, with comprehensive coverage of high-quality peer-reviewed journals in this domain. Second, this selection aligns with the core goal of our study: to construct a high-quality, internally comparable sample of peer-reviewed literature, which lays a solid foundation for the subsequent systematic synthesis. These databases are recognized for their rigorous inclusion standards and high scientific credibility [22, 27].

The Acquisition involves determining the search strategy and selecting the appropriate databases for material acquisition. In this study, literature was sourced from Scopus and the WoS. The search concluded on April 15, 2025, which marked the endpoint for article inclusion. Specifically, a combination of alternative keywords was used along with Boolean operators (AND and OR) and truncation symbols (e.g., *) to search for relevant research articles. Following the search strategies employed in prior studies [2, 15, 28], the search string- ((“academic entrepreneur*” OR “academic spin-off*” OR “university spin-off*” OR “academic startup*” OR “university startup*” OR “research commercialization” OR “technology commercialization” OR “patent licensing” OR “technology transfer”) AND (“healthcare” OR “medical” OR “clinical” OR “pharmaceutical” OR “biomedical”))- was applied to the “article title, abstract and keywords” within Scopus and WoS. Notably, the term “scientific entrepreneurship” and its variants were not included in the search string, for two core considerations related to conceptual boundary control and search accuracy. First, this study adopts a narrow definition of academic entrepreneurship in healthcare, which focuses specifically on commercialization activities initiated by academic institutions (universities, hospitals, research institutes) and their affiliated researchers, with patent licensing, technology transfer and academic spin-offs as the core forms. Second, the term “scientific entrepreneurship” in existing literature often covers a broader scope of science-based ventures and technology entrepreneurship, including many studies that do not involve academic subjects or the commercialization of academic research outcomes. Excluding this term helps to avoid sample noise caused by conceptual spillover, and ensures the consistency between the retrieved literature and the core conceptual focus of this study. A total of 14,757 records were identified through database searches (Scopus = 4,033; WoS = 10,724).

Arranging

Arranging involves the purification and organization of the collected literature. The purification involves inclusion and exclusion criteria. The inclusion criteria were as follows:

1. Document type: article;

2. Publication status: final;

3. Language: English;

4. Thematic relevance: the content must be closely related to academic entrepreneurship in healthcare.

Exclusion criteria were applied as follows:

1. Duplicate records;

2. Articles not specifically addressing academic entrepreneurship in healthcare, including:(i) studies on general entrepreneurship without academic involvement; (ii) studies on medical innovations lacking a focus on academic commercialization;(iii) studies on knowledge transfer that do not involve commercialization; (iv) studies on academic entrepreneurship without a healthcare-specific context.

3. Articles with unavailable full text. The inclusion and exclusion criteria were implemented through a standardized, independent dual-review process to ensure consistent and unbiased application. First, two authors independently screened the titles and abstracts of all retrieved literature against the above criteria, and excluded studies that clearly did not meet the requirements. Second, the full texts of the remaining literature were independently reviewed by the same two authors to make the final inclusion decision, with a focus on judging whether the study truly focused on academic entrepreneurship in healthcare, to avoid including general medical innovation studies, non-commercialization-oriented knowledge transfer studies, or entrepreneurship studies without academic subject participation. Any disagreements during the screening process were resolved through in-depth discussion with a third corresponding author. Following the application of the inclusion and exclusion criteria, a data-cleaning process was conducted, resulting in the exclusion of 14,672 documents. Consequently, 85 articles were retained for analysis.

In the stage of organization, all 85 research articles were coded and organized according to the APC framework which included (i) antecedents, (ii) phenomenon, (iii) consequences, and the TCM framework, which included (iv) theories, (v) contexts, (vi) methods. We first developed a standardized coding framework based on the six core dimensions of the APC and TCM frameworks. During the coding process, we repeatedly reviewed the full text of the included literature and the pre-specified classification standards. All coding results were cross-checked, and we ensured the consistency of classification and the reliability of the analysis through multiple rounds of review and in-depth discussion among all authors.

Assessing

The Assessing stage consists of evaluation and reporting. During the evaluation sub-stage, content analysis was employed to map and assess the following dimensions:(i) antecedents; (ii) phenomenon; (iii) consequences; (iv) theories; (v) contexts; and (vi) methods. A gap analysis was subsequently conducted across these dimensions to identify areas of underexplored research, thereby informing the development of a future research agenda.

In terms of reporting, multiple methods—including figures, tables, and narrative descriptions—were employed to present current insights into academic entrepreneurship in healthcare. The subsequent sections pinpoint knowledge gaps and outline future research directions. This study was funded by Guangxi Natural Science Foundation Collaborative Special Program on Active Health and Common & High-Incidence Diseases.

Framework-based review

The Theories, Contexts, and Methods (TCM) framework [25] and the Antecedents–Phenomenon–Consequences (APC) framework [26, 27] are used in this study.

The APC framework is designed to answer RQ1: What do we know about academic entrepreneurship in healthcare? It systematically sorts out the knowledge structure of academic entrepreneurship in healthcare from three dimensions: antecedents, phenomenon, and consequences, focusing on the structured integration of the research content itself.

The TCM framework is designed to answer RQ2: How do we know about academic entrepreneurship in healthcare? It examines how existing knowledge in the field is produced from three dimensions: theories, contexts, and methods, focusing on the reflective analysis of the foundation of knowledge production.

The integration of the two complementary frameworks enables us to identify critical literature gaps from both the “research findings” and “knowledge sources” levels, and then develop a targeted, evidence-based future research agenda to answer RQ3: Where should research go with academic entrepreneurship in healthcare?

Specifically, the APC framework serves as an effective instrument for organizing the literature. Antecedents refer to the factors that lead to the occurrence of the phenomenon, including both facilitators and barriers of academic entrepreneurship in healthcare; the phenomenon refers to the specific pathways academic entrepreneurship in healthcare; and consequences refer to the impacts resulting from academic entrepreneurship in healthcare (phenomenon). The TCM framework enables a evaluation of existing research on academic entrepreneurship in healthcare by analyzing its theories (T), contexts (C), and methods (M).

What do we know about academic entrepreneurship in healthcare (RQ1)

Publication trends on academic entrepreneurship in healthcare

An overview of publication trends is provided in Fig. 3. Between 1987 and 2006, scholarly output was minimal, with only 5 publications. A notable increase emerged during the period from 2007 to 2012, during which 14 relevant studies were published. This upward trend intensified further between 2013 and 2018, with 26 articles, indicating an expansion of research scope and methodological maturity. Most remarkably, the period from 2019 to 2025 witnessed an exponential rise in publications, accounting for nearly half of the total sample (n = 40). This surge can be attributed to the heightened focus on innovation and entrepreneurship in healthcare, coupled with the catalytic impact of global health emergencies like the COVID-19 pandemic [2, 3, 16].

Fig. 3.

Publication trends in academic entrepreneurship in healthcare from 1987 to 2025

Distribution of journal publications on academic entrepreneurship in healthcare

The 85 research articles on academic entrepreneurship in healthcare were published across 63 peer-reviewed journals. The highest concentration of research articles was found in Journal of Clinical and Translational Science (n = 9), followed by The Journal of Technology Transfer (n = 8). Other journals with multiple contributions include Research Policy (n = 4), International Journal of Entrepreneurship and Small Business (n = 2), Journal of Small Business and Enterprise Development (n = 2), Nature Biotechnology (n = 2), and Science and Public Policy (n = 2). The distribution of journal publications in academic entrepreneurship in healthcare is presented in Table 1.

Table 1.

The distribution of journal publications on academic entrepreneurship in healthcare

Journal Title	Number	Journal Title	Number
Journal of Clinical and Translational Science	9	Health Scope	1
The Journal of Technology Transfer	8	Heliyon	1
Research Policy	4	Higher Education	1
International Journal of Entrepreneurship and Small Business	2	IEEE Transactions on Engineering Management	1
Journal of Small Business and Enterprise Development	2	International Journal of Computer Assisted Radiology and Surgery	1
Nature Biotechnology	2	International Journal of Environmental Research and Public Health	1
Science and Public Policy	2	International Journal of Health Governance	1
Academic Radiology	1	International Journal of Information Science and Management (IJISM)	1
Acta Astronautica	1	International Journal of Innovation Management	1
Acta Medica Philippina	1	JACC: Basic to Translational Science	1
Advanced Biomedical Engineering	1	Journal of Commercial Biotechnology	1
Advanced Healthcare Materials	1	Journal of Dental Research	1
Annals of the American Thoracic Society	1	Journal of Developmental Entrepreneurship	1
Annals of Translational Medicine	1	Journal of Economic Behavior and Organization	1
Cambridge Journal of Regions, Economy and Society	1	Journal of Innovation and Entrepreneurship	1
ChemBioChem	1	Journal of International Entrepreneurship	1
Clinical and Translational Oncology	1	Journal Of Medical Engineering & Technology	1
Clinical and Translational Science	1	Journal of Medical Imaging and Radiation Sciences	1
Clinical Pharmacology & Therapeutics	1	Journal of Open Innovation: Technology, Market, and Complexity	1
COMMUNITY GENETICS	1	METHODS	1
Contaduría y Administración	1	mHealth	1
Entrepreneurship & Regional Development	1	Nanomedicine: Nanotechnology, Biology and Medicine	1
Entrepreneurship Research Journal	1	Organization Studies	1
Ethiopian Journal of Health Sciences	1	Patterns	1
Frontiers in Nanotechnology	1	PHARMACEUTICAL RESEARCH	1
Future Medicinal Chemistry	1	PLoS ONE	1
Global Public Health	1	Social Science and Medicine	1
Health Affairs Scholar	1	Social Studies of Science	1
Health Expectations	1	Technology in Society	1
Health Policy and Technology	1	Therapeutic Innovation and Regulatory Science	1
Health Research Policy and Systems	1	Topics in Spinal Cord Injury Rehabilitation	1
Translational Behavioral Medicine	1

Finding from APC framework

According to the APC framework [26, 27], antecedents refer to the enabling or constraining factors that influence academic entrepreneurship in healthcare.The phenomenon refers to the core commercialization pathways of academic entrepreneurship in healthcare, while the failure trajectories caused by multi-level constraining factors are incorporated into the antecedents dimension for systematic analysis. Consequences refer to the impacts of academic entrepreneurship in healthcare, encompassing both positive and negative effects.

Antecedents

Enabling factors

In this review, we identify seven categories of enabling factors for academic entrepreneurship in healthcare, derived from the analysis of 85 studies. These include: (i) individual enabling factors, (ii) team-level enabling factors, (iii) organizational enabling factors, (iv) policy enabling factors, (v) external collaboration and network enabling factors, (vi) market and demand enabling factors, and (vii) entrepreneurial process enabling factors (Table 2).

• (i).In terms of individual enabling factors, personal motivations, prior commercialization experience, availability of time and sustained personal commitment, and social capital as well as professional networks play a critical role in fostering academic entrepreneurial engagement.
• (ii).Team-level enabling factors, centered on the entrepreneurial team as the core collective actor, further facilitate entrepreneurial activities. The most critical team-level enabler is the construction of interdisciplinary teams integrating medical clinical practice, scientific research, engineering technology, business operation, legal and regulatory affairs, which complements the professional capabilities required for the whole cycle of medical research commercialization.
• (iii).Organizational enabling factors refer to the support from the host academic and medical institutions where the researchers are affiliated, including universities, hospitals and research institutions, rather than the new spin-off ventures formed after commercialization. Core enabling factors at this level include active and professional support from dedicated Technology Transfer Offices (TTOs), supportive organizational culture and incentive systems, as well as access to internal incubators, accelerators and seed funding resources.
• (iv).Policy enabling factors, such as government funding programs and favorable regulatory frameworks, provide essential financial resources and legitimize commercialization efforts.
• (v).External collaboration and network enabling factors, particularly university–industry–clinical partnerships and well-developed regional innovation ecosystems, provide an essential environmental foundation for academic entrepreneurship in healthcare.
• (vi).Market and demand enabling factors, including clear clinical needs and industry interest, enhance the research commercial viability of innovations in the healthcare domain.
• (vii).Finally, entrepreneurial process enabling factors, comprising entrepreneurship education and training, diversified funding access, pre-entrepreneurial evaluation and planning mechanisms, intellectual property protection, and established reimbursement pathways, are essential for successfully navigating research commercialization challenges in the healthcare sector.

Table 2.

Enabling factors of academic entrepreneurship in healthcare

Category	Enabling Factors	Representative References
(i)Individual enabling factors	Scientific reputation and productivity	[29–32]
	Entrepreneurial motivation (e.g., improving public health or securing research resources)	[33–35]
	Commercialization experience and competencies	[36–38]
	Social capital and professional networks	[29, 32, 38, 39]
	Availability of time and sustained personal commitment	[29, 34, 40, 41]
	Demographic factors (seniority, gender, family background)	[6, 42, 43]
(ii)Team-level enabling factors	Interdisciplinary teams (e.g., medicine, engineering, business, law, regulatory affairs)	[8, 9, 44, 45]
(iii)Organizational enabling factors	Active TTO support (e.g., patenting, licensing, commercialization strategy, technology assessment, incubation, and entrepreneurship training)	[46–49]
	Supportive organizational culture and incentives	[32, 37, 49–51]
	Access to incubators, accelerators, and seed funding	[10, 50, 52–54]
(iv)Policy enabling factors	Government funding programs (e.g., NCAI, REACH)	[55–58]
	Supportive legal and policies	[37, 57, 59–61]
(v) External collaboration and network enabling factors	University–industry–clinical partnerships	[47, 62–65]
	Regional entrepreneurial ecosystems (e.g., Silicon Valley, Oxford)	[32, 50, 66–68]
(vi)Market and demand enabling factors	Clear market demand and clinical feasibility	[50, 69–72]
	Industry interest and sustainable business models	[41, 73]
(vii)Entrepreneurial process enabling factors	Entrepreneurship education and training	[9, 74–77]
	Access to diverse funding sources	[45, 50, 52, 78]
	Early-stage entrepreneurial evaluation and strategic planning	[52, 79–82]
	Strong IP protection mechanisms	[7, 31, 52, 63]
	Established reimbursement and compensation mechanisms	[29, 64, 76, 80]

Notably, technology-related factors are not set as an independent category in this classification system, which is rooted in the unique contextual characteristics of academic entrepreneurship in healthcare reflected in the included literature. In the broader academic entrepreneurship field, the inherent attributes of technology are widely regarded as a core driver of entrepreneurial success. However, in the healthcare context, the commercial value of a technology is rarely determined solely by its own advancement. Instead, it is redefined and realized through a series of industry-specific mediating conditions: the clinical value of the technology needs to be verified through strict clinical trials, its market access needs to pass complex regulatory approval processes, its sustainable application relies on established medical insurance and reimbursement mechanisms, and its translation from laboratory to clinic requires the support of professional organizational structures such as TTOs. For this reason, the existing literature included in this review tends to discuss the role of technology embedded in these clinical, institutional, organizational and process factors, rather than treating technological attributes as an independent enabling factor category. This is itself a meaningful contextual finding that distinguishes academic entrepreneurship in healthcare from general academic entrepreneurship in other industries.

Constraining factors

Based on the analysis of 85 studies, this review identifies five categories of constraining factors that hinder academic entrepreneurship in healthcare (Table 3). These include individual constraining factors, such as limited time availability and low entrepreneurial motivation; organizational-level constraints, including insufficient institutional incentives and weak organizational support; and legal and regulatory challenges mainly related to complex and stringent regulatory processes for research commercialization in healthcare. Additionally, external collaboration barriers and underdeveloped innovation ecosystems, particularly in low- and middle-income countries, further restrict commercialization efforts. Finally, persistent funding shortages during early innovation stages remain critical obstacles within the entrepreneurial process.

Table 3.

Constraining factors of academic entrepreneurship in healthcare

Category	Constraining Factors	Representative References
Individual constraining factors	Lack of essential commercialization skills and experience	[50, 55, 66]
	Limited time availability and low entrepreneurial motivation	[7, 36, 60, 80, 83]
Organizational constraining factors	Inadequate TTO support and limited infrastructure	[47, 57, 79, 84]
	Rigid evaluation systems, internal bureaucracy, and Insufficient incentives and rewards	[10, 29, 32, 50, 83]
Legal and regulatory constraining factors	Complex and stringent regulatory processes	[85–88]
	Limited protection for non-patentable innovations	[66]
External collaborations and networks constraining factors	Ineffective Academia–Industry Collaboration Mechanisms	[37, 47, 57, 79]
	Structural Constraints in emerging and resource-limited economies	[41, 47, 87, 89]
Entrepreneurial process constraining factors	lack of funding in early innovation phases	[37, 47, 87, 90]

Further, the existing literature consistently shows that these multi-level constraining factors will lead to the stagnation, interruption and even complete failure of academic entrepreneurship in healthcare in different stages of the commercialization cycle. On the one hand, a large number of medical innovations with scientific value remain confined to the laboratory stage and fail to enter the formal commercialization pathway, due to the combined constraints of insufficient institutional support, limited commercialization competencies of researchers, and lack of early-stage funding. On the other hand, even for entrepreneurial attempts that have entered formal technology licensing negotiations or spin-off creation, these constraining factors will still lead to early termination of commercialization: for licensing pathways, the failure often occurs in the stages of clinical validation, regulatory approval, or industrial mass production; for spin-off pathways, the failure risks run through the whole life cycle of the venture, including long-cycle clinical trial financing difficulties, failure to obtain product market access approval, and mismatch between technology and actual clinical needs [47, 59, 68, 81, 91, 92].

Phenomenon

In this study, the phenomenon dimension of the APC framework captures the core implementation forms of academic entrepreneurship in healthcare triggered by multi-level antecedents, that is, the specific pathways through which academic institutions and their affiliated researchers commercialize medical research outcomes. Different from general academic entrepreneurship, the entrepreneurial pathways in the healthcare field present unique industry-specific characteristics shaped by strict clinical validation requirements, complex regulatory approval systems, and the inherent public welfare attributes of medical services. This section systematically sorts out the dominant commercialization pathways of academic entrepreneurship in healthcare, and focuses on revealing the special operation logic and process complexity of these pathways in the healthcare context.

Pathways of academic entrepreneurship in healthcare

This systematic literature review indicates that, under the combined influence of the aforementioned enabling factors, successful healthcare academic entrepreneurship practices predominantly follow two core pathways: external commercialization through technology or patent licensing agreements, and academic-led establishment of spin-offs. These two pathways, while sharing the core logic of academic research commercialization with general academic entrepreneurship, present distinct industry-specific characteristics and operation rules in the healthcare context, which are deeply shaped by the unique institutional environment and value attributes of the medical industry.

The first pathway is external commercialization through technology or patent licensing agreements. In this pathway, universities or research institutions typically commercialize their innovations externally by entering into exclusive or non-exclusive licensing agreements with industry partners. Different from the simple intellectual property transfer in general industries, the licensing practice of medical technologies presents three unique characteristics in the healthcare context. First, the core of licensing negotiation is not only the licensing fee and scope of use, but also the clinical feasibility verification and regulatory compliance guarantee of the technology, which are the core prerequisites for the effective implementation of licensing agreements [85, 88]. Second, the licensing process is deeply constrained by the public health attributes of medical technologies: for technologies related to major public health events or widespread diseases, the licensing model often needs to balance commercial benefits with the accessibility of medical technologies, rather than purely pursuing profit maximization [93, 94]. Third, the licensing of medical technologies usually involves long-term technical cooperation and follow-up support between academic institutions and industry partners, to adapt to the dynamic changes in clinical needs and regulatory policies throughout the technology application cycle [9, 45]. For example, through the coordinated efforts of its research teams and Technology Transfer Office, the University of Brasília effectively transformed the VESTA® respirator from a laboratory innovation into an industrial product by licensing it to Life Care Medical Indústria Comércio Eirelli [45]. Some cases have also adopted open-access or humanitarian licensing approaches to align with public health goals. For instance, Texas Children’s Hospital and Baylor College of Medicine provided their COVID-19 vaccine technology at low cost for use in developing countries, reflecting a public health-oriented licensing pathway for the translation of medical innovations [93].

The second pathway is academic-led establishment of spin-off ventures, which emphasizes the deep and continuous involvement of academic researchers in the whole entrepreneurial process. Compared with spin-off creation in general academic entrepreneurship, this pathway in the healthcare field faces a more complex and long-cycle commercialization process, and thus presents four distinct contextual characteristics. First, it relies heavily on the construction of interdisciplinary teams: the whole process from laboratory research to clinical application and market landing requires the continuous collaboration of medical clinical practice, scientific research, engineering technology, regulatory affairs, and business operation personnel, which is the core foundation for the survival and development of medical spin-offs [8, 44]. Second, the development of spin-offs is highly dependent on phased clinical validation and regulatory approval: unlike general technological innovations that can be quickly brought to the market, medical technologies need to pass multi-stage clinical trials and strict regulatory approval before they can achieve commercial transformation, which puts forward higher requirements for the spin-off’s ability to withstand long-term uncertainty and sustained financing capacity [85, 88]. Third, the value realization of spin-offs is more closely linked to the real clinical needs: the sustainable development of medical spin-offs does not depend solely on the advancement of the technology itself, but more on whether the technology can solve unmet clinical needs and be recognized by clinical institutions and medical practitioners [69, 73]. Fourth, the operation of spin-offs needs to balance the dual goals of commercial value and public health welfare, which is a core particularity that distinguishes them from general technology start-ups [49, 95]. For example, leading biomedical scientists at the Massachusetts Institute of Technology (MIT) founded 32 spin-off companies based on their laboratory discoveries, securing over $2 billion in venture capital funding through the phased clinical validation and commercialization of their technologies [32]. Similarly, companies such as KronosDNAsrl (KronosDNA) in Italy and Synendos Therapeutics in Switzerland were directly established by academic research teams to address specific unmet clinical needs, and achieved commercial success through interdisciplinary team collaboration and strict compliance with medical regulatory requirements [7, 9].

Consequences

Consequences are the results of academic entrepreneurship in healthcare, including both positive effects and negative effects.

Positive effects

Firstly, through academic entrepreneurship, a multitude of scientific discoveries are transferred into practically applicable products, such as COVID-19 vaccines, therapeutic drugs, and medical devices [40, 45, 89, 93, 96]. As a result, those products not only provide more treatment options for patients and improve the accessibility of healthcare services, but also enhance diagnostic efficiency, patient satisfaction, and clinical outcomes [9, 10, 40, 71]. Secondly, academic entrepreneurship in healthcare has inspired the establishment of medical start-ups and strengthened regional innovation ecosystems. A large number of spin-off companies originating from medical research have attracted substantial investment, and generated employment opportunities. These activities have contributed significantly to drive regional economic growth fostering innovation dynamics [7, 8, 32, 67]. Thirdly, through channels such as patent licensing, technology transfer agreements, and equity holdings in spin-off ventures, universities and research institutions can get financial revenues. In turn, these revenues from academic entrepreneurial activities are used as supporting fund to advance foundational medical research, thereby further promoting the development of fundamental research [66, 97, 98]. Finally, academic entrepreneurship activities also have fostered an innovation and entrepreneurial culture in the healthcare field. A wide range of academic entrepreneurship initiatives and training programs have effectively changed organizational and individual attitudes toward research commercialization, thereby increasing entrepreneurial awareness and interest among them [50, 52, 66]. Moreover, the early success of pioneering academic entrepreneurs has served as a catalyst, encouraging greater participation of researchers in academic entrepreneurship in healthcare [32].

Negative effects

Firstly, academic entrepreneurship in healthcare may lead to ethical controversies and risks to harm the public interest. On one hand, exclusive patent licensing can negatively impact the accessibility of medical technologies in less-developed economies [93]. Moreover, academic entrepreneurship activities by medical researchers may, either intentionally or unintentionally, cause research agendas to drift away from serving the public interest, potentially undermining patient welfare and broader public health priorities, which can pose challenges to medical ethics [7, 49, 94, 95]. Secondly, during the entrepreneurial process, academic researchers in the healthcare often face institutional tensions arising from the blending of multiple roles across research, teaching, clinical practice, and entrepreneurial activities, leading to identity conflicts [49]. In addition, researchers may also encounter dilemmas between the pursuit of academic freedom in publication and the need for commercial protection of intellectual property. Furthermore, unclear ownership of intellectual property and inequitable distribution of financial returns frequently result in conflicts of interest among universities, industries, and individual researchers [33, 46, 57]. Thirdly, the failure of academic entrepreneurship can result in significant resource waste. Substantial amounts of public funding are consumed during the early stages of technology transfer, but often fail to support products through later-stage clinical development or successful commercialization, leading to considerable resource inefficiencies [7, 36].

Through the systematic synthesis of the included literature, we identify four core distinctive characteristics of academic entrepreneurship in healthcare, which distinguish it from general academic entrepreneurship in other industries:

First, compared with general academic entrepreneurship, academic entrepreneurship in healthcare is more significantly influenced by organizational intermediary structures. Factors including dedicated Technology Transfer Offices (TTOs), professional incubation platforms, supportive organizational incentives and formal institutional support play a stronger bridging role in the whole process of medical research commercialization.

Second, entrepreneurial activities in the healthcare field are not purely driven by technology or market logic, but are deeply and jointly shaped by strict clinical validation requirements, complex regulatory approval processes, and the inherent public value attributes of medical services.

Third, existing research in this field has a clear success bias in narrative, with most studies focusing on the operation logic and practical cases of successful commercialization pathways, while paying relatively insufficient attention to the stagnation, interruption and failure trajectories of academic entrepreneurship in healthcare, as well as the multi-level constraining factors that lead to these failures.

Fourth, the outcomes of healthcare academic entrepreneurship present a more prominent “double-edged sword” attribute: on the one hand, it can effectively promote the translation of medical innovation and the realization of public health value; on the other hand, it may also trigger potential ethical risks, conflicts of interest, and inefficient allocation of public research resources.

These characteristics collectively demonstrate that academic entrepreneurship in healthcare is not a simple industry-level extension of general academic entrepreneurship, but a special commercialization field constrained by multiple institutional logics and public value requirements.

How do we know about academic entrepreneurship in healthcare (RQ2)

In line with the TCM framework, this section sheds light on the three components—(i) theories, (ii) contexts, and (iii) methods—to answer the question: how do we know about academic entrepreneurship in healthcare (RQ2)?

Theories

Theory plays a foundational role in social science by guiding research design, explaining phenomena, and enabling meaningful and applicable insights [99, 100]. However, only 13 studies on academic entrepreneurship in healthcare explicitly applied theoretical frameworks (Table 4), involving a total of 16 distinct theoretical lenses. The Theory of Planned Behavior was the most commonly used, appearing in two articles, while the remaining 15 theories were each applied in only one study, with some articles integrating multiple complementary theoretical frameworks.The theories identified in this study can be categorized into four major groups, as outlined below:

• (i)Individual-level theories, which emphasize how individual attitudes, capabilities, resources, and social relationships influence entrepreneurial intentions and behaviors. These include the Theory of Planned Behavior [105], Human Capital Theory [106], Social Capital Theory [107], and Network Theory [108].
• (ii)Organizational-level theories, which focus on how organizational resources, identity, and structural characteristics influence academic entrepreneurial behavior and strategic choices. These include the Resource-Based View [109], Organizational Identity Theory [110], and Organizational Imprinting Theory [111, 112].
• (iii)Institutional-and environmental-level theories, which examine how institutional structures, policy frameworks, and regional ecosystems shape academic entrepreneurial activities within healthcare settings. Relevant frameworks include the Triple Helix Model [113], the Regional System of Innovation [114], the Theory of Institutional Work [115], and Institutional Logics Theory [116, 117].
• (iv)Dynamic and evolutionary theories, which examine how academic entrepreneurial activities in healthcare evolve through non-linear, path-dependent, and network-driven processes. Key frameworks include Evolutionary Economic Theory [118], the Uppsala Internationalization Model [119] and International New Venture (INV) Theory [120], Evolutionary Game theory [121], and Stackelberg Game Model [122].

Table 4.

Prominent theoretical lenses on academic entrepreneurship in healthcare

Theory	Article(s)	Source
Theory of Planned Behavior	2	[38, 101]
theory of institutional work	1	[33]
Organizational identity theory	1	[83]
Resource-Based View	1	[30]
Organizational imprinting theory	1	[102]
A regional system of innovation	1	[32]
Uppsala Internationalization Model, International New Venture Theory	1	[89]
institutional logics theory	1	[49]
Evolutionary Economic Theory	1	[67]
Triple Helix model	1	[68]
Human Capital Theory, Social Capital Theory, Network Theory	1	[103]
Evolutionary Game theory,Stackelberg Game Model	1	[104]

Contexts

In this review, context is viewed as the situational setting in which the studies were conducted. A total of 85 articles were examined across three dimensions: countries, unit of analysis, subdomains. (Fig. 4 and Table 5).

Fig. 4.

Geographical distribution of research on academic entrepreneurship in healthcare

Table 5.

Contextual characteristics covered on academic entrepreneurship in healthcare

Context	n of articles	% of articles
Units of analysis
Organizations (e.g.,universities,research institutes, hospitals)	26	30.59%
Individuals (e.g., researchers, academic entrepreneurs)	23	27.06%
Entrepreneurial teams	15	17.65%
Spin-off firms or commercial companies	11	12.94%
Support programs or collaborative platforms	10	11.76%
Subdomains*
General Medical Devices	36	27.69%
Biologics–Vaccines/Immunotherapies	20	15.38%
Pharmaceuticals-Therapeutic Drugs	19	14.62%
In Vitro Diagnostics	17	13.08%
Software/AI as Medical Device	12	9.23%
Implantable Medical Devices	3	2.31%
General healthcare	23	17.69%

*Some studies cover multiple healthcare subdomains

In terms of countries, the reviewed 85 studies spanned 28 countries, including 8 studies that involved multiple national settings. The majority were conducted in the United States (38.95%, n = 37), followed by the United Kingdom (9.47%, n = 9) and Canada (8.42%, n = 8). Several studies originated from Switzerland, Sweden, Iran, and Italy (each 3.16%, n = 3), as well as the Netherlands, Mexico, Japan, Thailand, Singapore, Israel, Germany, and France (each 2.11%, n = 2). This distribution reflects a clear concentration in high-income countries with mature innovation systems, while also suggesting growing engagement from middle- and lower-income settings.

In terms of unit of analysis, most studies focused on organizations (30.59%, n = 26), such as universities, research institutes, hospitals, or their commercialization units (e.g., TTOs). Individuals, such as academic researchers, doctors and academic entrepreneurs, were examined in 27.06% (n = 23), and entrepreneurial teams in 17.65% (n = 15). Smaller shares of studies analyzed spin-off firms or commercial companies (12.94%, n = 11), and support programs or collaborative platforms (11.76%, n = 10).

In terms of subdomains of academic entrepreneurship in healthcare, among the 85 studies reviewed, 62 explicitly identified one or more specific healthcare subdomains, whereas the remaining 23 studies referred to the healthcare in general terms, without specifying a particular subdomain of healthcare. The most frequently cited subdomain was General Medical Devices, addressed in 36 studies, followed by Biologics–Vaccines/Immunotherapies (n = 20), Pharmaceuticals-Therapeutic Drugs (n = 19), and In Vitro Diagnostics (n = 17). Additional areas included Software/AI as Medical Device (n = 12) and Implantable Medical Devices (n = 3).

Methods

Based on the current review of 85 publications in academic entrepreneurship in healthcare, five main methodological categories were identified: qualitative, quantitative, conceptual, mixed methods, and non-specified (Table 6). Qualitative methods (n = 25) were the most frequently used and primarily included multiple case studies (n = 10), single case studies (n = 8), semi-structured interviews (n = 3), textual analysis (n = 2), discourse and narrative analysis (n = 1), and ethnographic designs (n = 1). Quantitative methods (n = 17) mainly involved regression-based techniques (n = 9) such as OLS, probit, logit, Tobit, Poisson, and Heckman models. Another six studies used descriptive and inferential statistics including Pearson correlation and the Friedman test. Bibliometric/database modeling (n = 1) and game-theoretic simulation (n = 1) were rarely employed. Conceptual papers (n = 20) developed models, frameworks, or normative arguments without direct data collection. Mixed methods design (n = 11) integrated both qualitative and quantitative tools. Twelve studies did not report an explicit methodological approach. Overall, the field shows a strong reliance on case-oriented qualitative research, complemented by conceptual research and quantitative methods. Future work could benefit from greater uptake of longitudinal, and mixed-methods designs.

Table 6.

Research approaches in academic entrepreneurship in healthcare

Research approach	n of articles	% of articles
Conceptual	20	23.53%
Qualitative	25	29.41%
Single Case Study	8	9.41%
Multiple Case Study	10	11.76%
Semi-structured Interview	3	3.53%
Textual Analysis	2	2.35%
Discourse and Narrative Analysis	1	1.18%
Ethnographic Study	1	1.18%
Quantitative	17	20%
Descriptive and Basic Statistical Analysis (e.g., Pearson correlation analysis, Friedman’s test)	6	7.06%
Regression Analysis (e.g., OLS, Logit, Probit, Tobit, Poisson)	9	10.59%
Bibliometric and database modeling	1	1.18%
Game-Theoretic Modeling and Simulation	1	1.18%
Mixed methods	11	12.94%
No Explicit Research Method	12	14.12%

Future research agenda (RQ3)

Building on the findings presented in the preceding sections (RQ1 and RQ2), this section addresses the question of where should research go with academic entrepreneurship in healthcare (RQ3). Different from the simple directional listing in the original manuscript, the revised future research agenda follows a problem-oriented logic: for each research direction, we not only point out the content worthy of further exploration, but also clarify its research significance, core research questions, and how it addresses the limitations of existing research, so as to better guide the follow-up research development in this field. The agenda is structured around three dimensions: (i) new theoretical perspectives, (ii) expanded research settings, and (iii) diversified methodological approaches.

New theoretical perspectives for academic entrepreneurship in healthcare

Existing research on academic entrepreneurship in healthcare, as reviewed in this study, has drawn on various theoretical frameworks. However, the overall theoretical foundation remains relatively narrow, with only 16 distinct theories identified. The limited use of theories signals an important gap, suggesting the need for broader theoretical perspectives to enrich future research. Building on the identified theoretical gaps, the following sections outline potential theoretical frameworks that future research could leverage, organized across the individual, organizational, and institutional/environmental levels.

At the individual level, future research could draw on Person-Environment Fit Theory [123] to examine how the alignment between individual researchers’ value orientations, knowledge and skills, and role expectations and the academic entrepreneurial support environment within organizations influences their entrepreneurial pathway choices in the healthcare domain. Such alignment or misalignment may serve to either facilitate or hinder researchers’ engagement in healthcare academic entrepreneurial activities. In addition, Role Conflict Theory [124] offers a promising perspective for future research to examine how conflicts among multiple roles—such as physician, researcher, and entrepreneur—affect healthcare researchers’ entrepreneurial intentions, decision-making behaviors, and the sustainability of their role transitions. Furthermore, future research could also use Regulatory Focus Theory [125] to examine how promotion-focused versus prevention-focused motivational orientations affect healthcare researchers’ risk assessments and entrepreneurial behavior.

At the organizational level, future research could use Dynamic Capabilities Theory [126] to guide how universities, medical institutions, reconfigure their resources to strengthen organizational dynamic competencies and effectively adapt to rapidly changing technological, regulatory, and market environments, and then foster academic entrepreneurship in healthcare. Moreover, Ambidexterity Theory [127, 128] and Organizational Paradox Theory [129] provide valuable perspectives for understanding how organizations balance the tension between competing activities or institutional logics. Future research could explore how organizations, especially healthcare institutions, build mechanisms that manage competing institutional logics, such as the tension between clinical service missions and entrepreneurial commercialization goals.

At the institutional and environmental level, Public Value Theory [130] could offer a valuable framework for future research to assess whether academic entrepreneurial initiatives in healthcare genuinely respond to public value rather than merely advance private or institutional interests. Moreover, future studies could also employ the Actor–Network Theory (ANT) [131] to analyze how heterogeneous elements—including individuals, organizations, institutional arrangements, funding, laboratory equipment, and incubation platforms—interact through collaborative networks to facilitate the commercialization of medical innovations.

Furthermore, the rapid development of generative artificial intelligence technologies like ChatGPT and DeepSeek is promoting academic entrepreneurship in healthcare to shift from tangible outputs toward the creation of digital assets. Future research could incorporate the Theory of Digital Objects [132] and Sociotechnical Systems Theory [133] to systematically explore the value construction mechanisms of non-patentable digital innovations and the organizational adaptation pathways for human–machine collaboration. By doing so, scholars can expand the theoretical boundaries of academic entrepreneurship in healthcare and deepen the understanding of emerging commercialization mechanisms in the digital era.

Expanded research settings for academic entrepreneurship in healthcare

Current research on academic entrepreneurship in healthcare has predominantly focused on elite universities and research-intensive hospitals in developed countries such as the United States, Canada, and the United Kingdom. The literature tends to emphasize successful cases and patent-based commercialization pathways, while paying relatively little attention to diverse contexts such as developing countries and instances of entrepreneurial failure. Therefore, future research is urgently needed to expand investigations into the following critical contexts:

First, greater scholarly attention should be directed to academic entrepreneurship in healthcare in low- and middle-income countries (LMICs). Existing studies are overwhelmingly concentrated in high-income countries with mature national innovation systems, a geographical bias that severely limits our understanding of how medical research commercialization functions in resource-constrained contexts. To address this gap, future research should explore the alternative entrepreneurial pathways and context-specific adaptive strategies that enable medical innovation commercialization in LMICs, even in the face of inadequate infrastructure, limited financing, and weak institutional support. This line of inquiry will not only enrich the contextual boundaries of the field, but also provide actionable insights for promoting healthcare innovation in emerging economies.

Second, future research should extend its analytical focus beyond elite universities and tertiary hospitals to under-resourced academic medical centers and primary care institutions. Most existing work centers on well-resourced, research-intensive institutions, while overlooking the innovation potential of frontline medical institutions with limited research resources, resulting in an incomplete portrait of entrepreneurial subjects in this field. A key research question to address is how under-resourced medical institutions can initiate or participate in the commercialization of healthcare innovations, despite constraints in infrastructure, funding, and institutional support. This work will help identify inclusive models of academic entrepreneurship in healthcare that are not limited to elite institutional settings.

Third, future inquiry should expand beyond academic researchers to examine the entrepreneurial potential of the full spectrum of healthcare practitioners, including clinicians, nurses, pharmacists, public health experts, and medical AI engineers. These frontline practitioners hold unique insights into unmet clinical needs, yet their entrepreneurial behaviors, motivations, and barriers remain largely underexplored in the existing literature. Core research questions in this area include what institutional and organizational mechanisms can effectively encourage non-research medical practitioners to engage in academic entrepreneurship, and what unique characteristics define their entrepreneurial pathways compared to traditional academic researchers. This direction will fill a critical gap in our understanding of the diverse actors driving academic entrepreneurship in healthcare.

Fourth, future research should move beyond a narrow focus on patent-based commercialization pathways to examine the commercialization of non-patentable knowledge assets and digital innovations. With the rapid development of generative artificial intelligence and digital health, medical innovations are increasingly taking the form of clinical algorithms, digital therapeutics, data platforms, and decision support tools, yet existing research has paid insufficient attention to the commercialization mechanisms of these non-patentable assets. A key line of inquiry will be to identify viable commercialization pathways and governance models for non-patentable digital medical innovations, while also exploring how existing intellectual property and regulatory systems can be adapted to this emerging trend. This direction will ensure that the field keeps pace with the evolving landscape of medical innovation.

Fifth, future research should further explore the role of technological attributes in academic entrepreneurship in healthcare, and unpack the interaction mechanism between technology heterogeneity and multi-level contextual factors in the healthcare industry. Existing research has not yet systematically examined how the inherent attributes of medical technologies (such as technical maturity, innovation radicalness, technical complexity, and non-patentability) shape entrepreneurial pathway choices and commercialization outcomes. Future studies could investigate how different technological attributes interact with clinical validation requirements, regulatory systems, organizational support structures, and market demand to jointly influence the development of academic entrepreneurship in healthcare, to reveal the unique value realization logic of medical technologies in the entrepreneurial process.

Finally, existing research predominantly focuses on successful cases of academic entrepreneurship in healthcare, while failure trajectories remain largely underexplored. Future studies could investigate how individuals navigate psychological adjustment processes following academic entrepreneurial failure, how organizations engage in post-failure learning and capability development, and how institutional environments adapt through feedback mechanisms to better support subsequent entrepreneurial efforts.

Diversified methodological approaches for academic entrepreneurship in healthcare

Although existing research has made important strides in advancing the understanding of academic entrepreneurship in healthcare, several methodological limitations remain evident. Qualitative and conceptual studies (n = 45) continue to dominate the field, while quantitative research is often based on cross-sectional data, thereby lacking a longitudinal evolutionary perspective. In addition, although mixed-methods studies exhibit emerging potential, their number remains limited (n = 11). Moreover, 12 studies did not explicitly report their research methods. To advance methodological innovation, future research could be expanded along the following four directions:

The most pressing methodological need is the adoption of longitudinal research designs that track the full commercialization trajectory of medical innovations from laboratory to market. Most existing studies rely on cross-sectional data or retrospective case analyses, which are unable to capture the dynamic evolution of entrepreneurial activities across different stages of commercialization, or identify the critical inflection points that drive success or failure. Longitudinal case studies, multi-wave panel surveys, and real-time tracking of entrepreneurial projects will enable scholars to unpack how enabling and constraining factors shift across the commercialization lifecycle, and how different actors interact over time to shape entrepreneurial outcomes.

To unpack the multi-level causal mechanisms of academic entrepreneurship in healthcare, future research should leverage advanced quantitative methods including multilevel modeling, structural equation modeling (SEM), and fuzzy-set qualitative comparative analysis (fsQCA). Existing quantitative work largely relies on simple single-level regression models, which cannot account for the nested nature of entrepreneurial phenomena—where individual behaviors are embedded within team, organizational, and institutional contexts. These advanced quantitative methods will allow researchers to test the interactive effects of factors across multiple levels, identify the core configurations of conditions that drive successful commercialization, and verify the generalizability of theoretical models across different contexts.

Future research should also prioritize sequential mixed-methods designs that integrate qualitative and quantitative approaches to address the complex, multi-faceted nature of academic entrepreneurship in healthcare. The limited number of mixed-methods studies in the field means that scholars have yet to fully leverage the complementary strengths of qualitative and quantitative research: qualitative methods can uncover new phenomena and generate theoretical insights, while quantitative methods can verify the generalizability of these insights across larger samples. A recommended design is to first conduct in-depth semi-structured interviews with academic entrepreneurs, institutional managers, and policymakers to explore the core mechanisms of academic entrepreneurship in healthcare, then use large-scale survey data to quantitatively test and refine the resulting theoretical model. This approach will produce more robust, rigorously validated findings than single-method designs.

Finally, cross-context comparative research designs will be critical to advancing the generalizability of research findings in the field. Most existing studies focus on single cases, single institutions, or single national contexts, which limits the extent to which findings can be generalized across different settings. Multi-case comparative studies across different national contexts, institutional types, and healthcare subdomains will enable scholars to distinguish between the universal laws of academic entrepreneurship in healthcare and context-specific idiosyncrasies. For example, comparative studies between high-income countries and LMICs, or between elite academic medical centers and under-resourced institutions, will help identify which support mechanisms are universally effective and which need to be adapted to specific contexts.

In doing so, scholars will be better equipped to capture the evolving and complex nature of academic entrepreneurial processes in the healthcare domain.

Conclusion

While research on academic entrepreneurship in healthcare is rapidly growing, the existing literature remains fragmented and lacks a comprehensive synthesis of its progress and future directions. To address this gap, this review systematically examined 85 peer-reviewed studies by applying the APC framework and the TCM framework to answer three central research questions: (RQ1) What do we know about academic entrepreneurship in health? (RQ2) How do we know about academic entrepreneurship in healthcare? and (RQ3) Where should future research go with academic entrepreneurship in health? Based on the APC framework, this review systematically examines the enabling and constraining factors, commercialization pathways, and impacts of academic entrepreneurship in healthcare. By applying TCM framework, this review systematically examines the theoretical foundations, contextual settings, and methods of existing research on academic entrepreneurship in healthcare, based on which research gaps are identified and a future-oriented research agenda is proposed.

Core findings of the review

Guided by the SPAR-4-SLR protocol and the complementary APC and TCM dual frameworks, this systematic review analyzes 85 high-quality peer-reviewed studies on academic entrepreneurship in healthcare, and yields four core findings that form the complete logical thread of the paper:

First, research on academic entrepreneurship in healthcare has experienced exponential growth since 2019, but the theoretical foundation of the field remains relatively narrow. Most existing studies apply general academic entrepreneurship theories, without fully considering the unique contextual characteristics of the healthcare industry.

Second, academic entrepreneurship in healthcare is driven by multi-level enabling factors, and is constrained by a core structural tension between the public welfare attribute of medical innovation and the commercial logic of entrepreneurial activities. This is the most distinctive feature that distinguishes it from general academic entrepreneurship in other industries.

Third, the core commercialization pathways of academic entrepreneurship in healthcare include external technology/patent licensing and academic-led spin-off creation, both of which present unique industry characteristics shaped by strict clinical validation requirements, complex regulatory approval processes, and public health value orientation.

Fourth, existing research is highly geographically concentrated in high-income developed countries and elite medical institutions, with insufficient attention to low- and middle-income countries, under-resourced medical institutions, non-academic entrepreneurial actors, and entrepreneurial failure trajectories.

Theoretical contributions

Theoretically, this study makes three key contributions to the field of healthcare academic entrepreneurship, all of which are rooted in the complementary integration of the APC and TCM dual frameworks. Unlike previous single-framework literature reviews that can only reveal partial characteristics of the field, the combined application of the APC and TCM frameworks in this study enables a full-dimensional, systematic understanding of healthcare academic entrepreneurship. Specifically, the APC framework constructs a complete portrait of “what the field has explored” from the core content level, while the TCM framework reveals “how existing knowledge in the field is produced” from the knowledge production paradigm level. The integration of these two complementary frameworks not only forms a closed logical loop for the three core research questions of this paper, but also supports the identification of deep-seated knowledge gaps in the field, rather than the superficial listing of research deficiencies in most existing reviews. The specific theoretical contributions are detailed as follows:

First, this study breaks the single-framework analysis model widely used in existing reviews in this field, and constructs an integrated analytical model for healthcare academic entrepreneurship based on the complementary dual frameworks of APC and TCM. Unlike previous studies that mostly apply multiple frameworks in a parallel and isolated manner, this study clarifies the inherent complementary logic between the two frameworks: the APC framework systematically sorts out the content system of existing research to answer the core question of “what do we know about academic entrepreneurship in healthcare”, while the TCM framework evaluates the knowledge production paradigm of the field to answer the second core question of “how do we know about academic entrepreneurship in healthcare”. This integrated analytical model breaks the limitation of fragmented analysis in existing reviews, and provides a holistic, multi-dimensional and logically consistent analytical perspective for future research in this field.

Second, our comprehensive findings demonstrate that the explanatory logic of general academic entrepreneurship research cannot be simply transplanted and applied to the healthcare context. Academic entrepreneurship in healthcare must fully consider the industry’s unique institutional environment, inherent public value orientation, strict multi-stage clinical validation requirements, and complex regulatory approval system, which are fundamentally different from the general academic entrepreneurship scenario in other industries. We confirm that healthcare academic entrepreneurship is a compound phenomenon that integrates entrepreneurial commercial logic, academic research logic, and medical public welfare responsibility logic. This core finding breaks the long-standing limitation that existing studies simply transplant general academic entrepreneurship theories to the healthcare context without fully considering the industry’s contextual specificity, and highlights the necessity of developing a more context-sensitive, industry-adapted analytical framework for this specific field in future research.

Third, this study systematically maps the full knowledge map of healthcare academic entrepreneurship for the first time. It integrates the multi-level antecedents (enabling and constraining factors), core commercialization pathways, multi-dimensional consequences, theoretical foundations, research contexts, and methodological approaches of the field into a unified analytical system. This systematic integration solves the long-standing problem of fragmented literature in the field of healthcare academic entrepreneurship, clarifies the core logical thread of existing research, and lays a solid and systematic theoretical foundation for subsequent in-depth empirical research and theoretical expansion in this field.

Practical implications for multi-stakeholders

In line with the core goal of this study to “bridge research and practice”, this review provides targeted, actionable practical guidance for three core stakeholders in academic entrepreneurship in healthcare. We emphasize that promoting high-quality development of academic entrepreneurship in healthcare cannot only stay at the level of encouraging researchers’ entrepreneurial awareness, but requires the simultaneous improvement of multi-dimensional support structures. Only with these sound supporting systems in place can the commercialization of medical research achievements be effectively advanced.

For national and industry policymakers

Policymakers should move beyond macro policy guidance to build a full-cycle institutional support system for academic entrepreneurship in healthcare. First, it is necessary to optimize the regulatory approval process for academic-derived medical innovations, and establish a fast-track approval mechanism for patent licensing and spin-off products from academic medical institutions. Second, improve the intellectual property governance system that balances commercial value and public health interests, and formulate targeted policies to support the commercialization of non-patentable digital medical innovations such as clinical algorithms and digital therapeutics. Third, improve the supporting policies for industry-university-clinic collaborative innovation, set up special funding programs for the early-stage commercialization of medical research results, and establish a governance framework that takes into account both medical ethics and public interests, to break the institutional barriers between laboratory research and clinical commercialization.

For university, hospital and research institution managers

Institutional managers should not only focus on encouraging researchers’ entrepreneurial awareness, but build a sound full-process organizational support system. First, establish and professionalize the Technology Transfer Office (TTO), to provide one-stop support including patent application, licensing negotiation, commercialization planning, and entrepreneurial incubation for researchers. Second, optimize the interdisciplinary team cooperation mechanism, performance evaluation and incentive system, include the commercialization of medical research results into the academic evaluation system, and set up a reasonable profit distribution mechanism to stimulate the sustainable entrepreneurial motivation of researchers. Third, build professional innovation platforms and entrepreneurship incubation bases, carry out targeted entrepreneurship education and training, and establish a reasonable failure tolerance mechanism to support post-failure learning and re-entrepreneurship.

For frontline researchers, clinical practitioners and innovation platform practitioners

For frontline practitioners, high-quality academic entrepreneurship relies on both the improvement of individual comprehensive capabilities and the support of the above-mentioned multi-level institutional and organizational systems. First, researchers should conduct in-depth early clinical demand and market feasibility assessment before launching entrepreneurial activities, to avoid the disconnection between laboratory research and real clinical needs. Second, actively build interdisciplinary teams integrating clinical practice, technology R&D, regulatory affairs and business operation, to complement the knowledge and capabilities required for the whole cycle of medical research commercialization. Third, make full use of the supporting resources provided by the institution and government, and always maintain the balance between the commercial value of entrepreneurial activities and the public welfare attribute of medical innovation, to effectively avoid ethical risks and conflicts of interest in the commercialization process.

Limitations of the study

While this review offers a comprehensive synthesis of academic entrepreneurship in healthcare, several limitations should be acknowledged. First, the review included only peer-reviewed studies published in English and retrieved from Scopus and Web of Science. Although this selection enhances the quality and comparability of the included studies, it may lead to the omission of relevant studies published in other languages or from other databases, which is a common limitation of systematic literature reviews in this field.

Second, to ensure conceptual clarity and analytical focus, this study adopts a relatively narrow definition of academic entrepreneurship in healthcare, focusing exclusively on two core commercialization forms: academic spin-off creation and patent/technology licensing. Therefore, activities such as contract research, industry consulting, and non-commercial university-industry collaborations are not included in the analytical scope, which may not fully capture the full diversity of academic entrepreneurial behaviors in the healthcare field. This definitional boundary is a core limitation of the study, and future research could expand the scope to explore more diverse forms of academic entrepreneurship in healthcare.

Concluding remarks

Against the background of the rapid development of academic entrepreneurship in healthcare and the long-standing fragmentation of existing literature, this study provides a systematic, framework-based synthesis of the current status, core findings, and critical knowledge gaps in this field. By integrating the complementary APC and TCM dual frameworks, this review not only clarifies the unique characteristics and development laws of academic entrepreneurship in healthcare, but also constructs a comprehensive, problem-oriented future research agenda. Ultimately, this study aims to bridge the persistent gap between academic research and industry practice in this field, and provide theoretical support and practical guidance for promoting the high-quality development of academic entrepreneurship in healthcare.

Author contributions

Huang Min: Literature Review, Writing-Original Draft, Yang Guofeng: Data Analysis，Conceptualization, Chen Yan and Fang Mei: Methodology, Supervision, Chen Wenda: Literature Review, Du XuePeng:Data Analysis.

Funding

This research was supported by the Science and Technology Program of Guangxi Provincial Disease Control and Prevention Administration (GXJKKJ2025YB008).

Data availability

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Declarations

Ethics declaration

Not Applicable.

Institutional review board statement

Not Applicable.

Informed consent statement

Not Applicable.

Consent for publication

Not Applicable.

Competing interests

The authors declare no competing interests.