The application prospect of microneedles for sports injuries: a narrative review

Abstract

Background

The increasing participation in sports, driven by the popularity of physical activity and advancements in sports science, has led to a rise in sports injuries. Traditional treatments for sports injuries typically involve physical therapy and pharmacological interventions. However, drug therapy often suffers from low bioavailability, and analgesic and anti-inflammatory medications may also cause side effects such as gastrointestinal irritation and cardiovascular risks. To amplify the range of therapeutic options in the domain of sports injuries, microneedles (MNs) have emerged as a promising alternative.

Methods

A comprehensive review of English literature from the past two decades and more was performed across multiple databases, including PubMed, Embase, and Web of Science. The search utilized the keywords ‘microneedle,’ ‘sports injury,’ ‘drug delivery,’ etc. Original research articles, clinical studies, and reviews pertinent to the subject were included, while irrelevant and duplicate publications were excluded from the analysis.

Results

The diverse types and materials of MNs make them promising tools for treating sports injuries. These applications facilitate not only the targeted delivery of pharmaceuticals and biological materials but also enable continuous medical supervision through the assessment of subcutaneous metabolites.

Conclusion

The application of MNs in the management of sports injuries holds significant promise for therapeutic interventions and medical monitoring, offering valuable insights for future innovation in sports science applications.

1. Introduction

With the continuous development of society and the improvement of people’s awareness of health, exercise has gained growing popularity and importance across all age groups as a means of promoting physical well-being [1]. However, both professional and amateur athletes still face a high incidence of sports-related injuries [2–4]. Common types of sports injuries encompass those related to muscle/tendon, nerve, bone, cartilage/synovium/bursa, ligament/joint capsule, and superficial tissues/skin [5]. Prompt and effective evaluation and treatment are essential once sports injuries occur, particularly for professional athletes.

The fundamental approaches for treating sports injuries mainly involve active rehabilitation programs. These programs incorporate a range of techniques, including stretching, cryotherapy, electrical stimulation, compression, and strengthening exercises [6]. Additionally, pharmacological treatments are often employed as supplementary interventions and are crucial in the overall management of sports injuries. Numerous medications are commonly prescribed for the management of musculoskeletal conditions and sports-related injuries, such as analgesics and non-steroidal anti-inflammatory drugs [7]. However, oral administration of these drugs presents several challenges, such as gastrointestinal irritation and unpredictable release properties [8]. Conversely, transdermal administration has the advantages of more convenient administration and avoiding the first-pass effect and gastrointestinal irritation [9]. However, transdermal administration requires overcoming the resistance barrier of the skin to improve the bioavailability of the drug [9].

Microneedles (MNs) can pierce the epidermis to deliver drugs directly to the dermis. They are primarily used to pierce the skin in a minimally invasive manner through a small array of tips, enabling transdermal drug delivery [10]. Additionally, MNs can transport not only pharmaceutical agents, but also various other biomaterials such as cells, exosomes, nucleic acids, and similar substances [11]. In recent years, there has been a surge of interest in the application of MNs in various fields, such as tumor treatment, vaccine administration, and chronic disease management [12–14]. MNs have also been extensively studied and applied in biosensing and medical diagnosis [15,16].

This review discusses the potential use of MNs in treating sports injuries, encompassing muscle/tendon, bone/cartilage, ligament/joint capsule, superficial tissues/skin, and nervous injuries (Table 1). The detailed search process for the core literature can be found in the supplementary file. This review explores the therapeutic potential of MNs in the management of sports injuries, highlighting their advantages demonstrated in preclinical studies. These findings provide valuable guidance for the future clinical application of MNs in sports injury treatment. In addition, we discuss the emerging role of microneedle-based biosensing technologies, emphasizing their potential to enable real-time monitoring of sports-related biomarkers. Such capabilities offer new insights into their application in both injury rehabilitation and real-time physiological assessment, further expanding the role of MNs in sports medicine (Figure 1).

Table 1.

Microneedle therapy for sports injury-related diseases.

Tissue	Content	Classification	Disease	MN dimension	Drug dose	Utilization ratio of drug	Mechanical properties	Key outcome	Wound closure	Literature
Muscle or tendon	Platelet derived growth factor	Soluble and polymers	Tendon injury	–	2 μg	80%	18N	Gastrointestinal side effects, liver first-pass effects	–	Liu et al. [64]
	Carbonized wormwood and prostaglandin E2	Soluble and polymers	Damaged skeletal muscles	800 μm	300 μg	–	4N	Pain, respiratory infections, scalding	24h	Zhang et al. [62]
	Exosomes/nitric oxide nanomotor	Soluble and polymers	Achilles tendinopathy	–	300 µg	–	0.5N	Gastrointestinal side effects	–	Liu et al. [60]
Bone or cartilage	Recombinant human growth hormone	Solid and polymers	Short stature	1,350 μm for rats + 600 μm for mice	789 μg for rats + 78 μg for mice	Programmed drug release	similar mechanical properties to those of native skin tissues	Poor compliance, Potential risk of infections	100min	Han et al. [76]
	Trans-aconitic acid	Degradable and polymers	Inflammatory diseases	780 μm	150 μg or 1050 μg	67%	0.18N	Systemic toxicity, adverse reactions	–	Lin et al. [70]
Ligament or joint capsule	hEGF/methotrexate	Soluble and polymers	Joint injury	800 μm	–	–	–	Acute kidney injury, gastrointestinal tract damage, toxic side effects	–	Li et al. [87]
	Vascular endothelial growth factor	Soluble and polymers	Skin wound	650 μm	–	77.60%	0.33N	Hemolysis, biotoxicity	–	Fan et al. [90]
	Mesenchymal stem cell	Soluble and polymers	Skin wound	700 µm	4.5 × 10³ cells	–	1N	Invasive, scar tissue, low engraftment efficiency	–	Lee et al. [139]
	Astragalus membranaceous polysaccharide nanoparticles	Soluble and polymers	Skin wound	600 μm	85.17%	83.99%	0.29N	Cytotoxicity, Acterial resistance, Low immunogenicity, Low bioavailability	30min	Liu et al. [92]
	Mussel adhesive protein	Soluble and polymers	Skin wound	750 μm	300 μg	–	1.75N	Local ischemia, necrosis, scar formation, infection, air/fluid leakage	–	Jeon et al. [97]
Nervous	Epigallocatechin gallate	Soluble and metals	Spinal cord injury	800 μm	714.92 ± 14.26 μg	–	>32N	Blood–spinal cord barrier limitation, low bioavailability, systemic toxicity, necrotic tissue exacerbation	30min	Chen et al. [109]
	Peripheral	Soluble and polymers	Neuropathic pain	850 µm	–	90%	≈0.89 N	Dizziness, drowsiness, cognitive impairment		Zhang et al. [112]
	Buprenorphine Hydrochloride	Soluble and polymers	Neuropathic pain	900 μm	318μg	–	–	Respiratory depression, Constipation, Immunosuppression, Drug resistance	20min	Han et al. [113]
	Poly(S-nitrosoglutathione)	Solid and polymers	Traumatic brain injury	–	4.2 nmol/mg	–	–	Inflammation, Neurotoxicity	–	Chiang et al. [102]
	NO donor (poly(S-nitrosoglutathione), pGSNO)	Solid and metals	Traumatic brain injury	–	–	on-demand release	–	Glial scar	–	Chiang et al. [102]
	Mesenchymal stem cell	Soluble and polymers	Spinal cord injury	300 μm	200 μg	–	500 kPa	Low bioavailability	–	Han et al. [106]
	Methylprednisolone sodium succinate	Soluble and polymers	spinal cord injury	300 μm	400 μg	60.49–72.66%	0.079N	Gastrointestinal bleeding, Hyperglycemia, Hypertension, Osteoporosis, Infections	–	Zhai et al. [107]
	Extracellular vesicles	Soluble and polymers	Spinal cord injury	600 μm	1 × 10^6 cells	–	matching soft spinal tissues	Inflammation, MSC invasion, Coughing	–	Fang et al. [108]
	Calcitonin gene related peptide	Soluble and polymers	Neuropathic pain	800 μm	1.42 ± 0.65 μg	91.5 ± 15.3%	–	Systemic side effect, Low bioavailability, Short half-life in blood circulation	–	Xie et al. [110]
	Ziconotide-loaded liposomes fused with exosomes	Soluble and polymers	Neuropathic pain	800 μm	1 mg/mL	≈100%	>1N	Postural hypotension, Dizziness, Sinus bradycardia, Rhinitis, Nausea	60min	Song et al. [111]

Figure 1.

Microneedle types and their application in sports injuries.

2. Classification and material properties of microneedles

MNs have undergone various iterations since it was proposed. Presently, there are three main types of MNs based on the mode of drug delivery: solid, hollow and soluble polymer MNs (Figure 1) [17]. Moreover, MNs can be fabricated from a wide range of materials, primarily including inorganic non-metals, metals, and polymers [18].

2.1. Classification of microneedles

2.1.1. Solid microneedles

Solid MNs are the earliest type of MN application. These are typically made of inorganic non-metallic materials or metals [19,20]. The main purpose of solid MNs is to create tiny channels in the skin and apply drugs. Additionally, treatment can be administered by applying a drug directly onto the surface of the MNs [21].

2.1.2. Hollow microneedles

The hollow MNs are a special type of microinjection needle that has a unique hollow structure. Unlike other MNs, these are designed for delivering fluids to the skin, similar to subcutaneous injections. They are primarily utilized for delivering macromolecular drugs and high-dose drugs [22]. Additionally, the flow rate of the hollow MNs can be adjusted by controlling the pressure, allowing for rapid injection, slow infusion, or variable speed delivery [23].

2.1.3. Soluble or degradable microneedles

Currently, soluble or degradable MNs are frequently utilized in the field of medicine [24,25]. These MNs have the ability to encase drugs within a polymer matrix, which subsequently completely dissolves or swells upon insertion into the skin. The significant benefit of using polymer MNs is that they do not leave behind any biohazardous sharp waste after use [26]. Additionally, these MNs offer advantages such as excellent biocompatibility, low toxicity, high flexibility, and cost-effectiveness.

2.2. Material properties of microneedles

2.2.1. Inorganic non-metals

Silicon and ceramics are commonly used as inorganic non-metallic substrates for MNs [27]. These materials offer excellent mechanical strength, high precision in fabrication, and chemical stability, making them suitable for applications where long-term durability and precise drug delivery are required [28].

Among them, silicon microneedles have been the most widely used type. The fabrication of MNs using silicon and silicon-based materials is typically achieved through isotropic and anisotropic corrosion processes [29]. If the strength is not sufficient, it can lead to unfavorable reactions like inflammation or infection, caused by leftover debris within the body. The preparation of ceramic MNs typically involves using dual-replicated Polydimethylsiloxane (PDMS) production molds and ceramic micro-molding technology. However, the crucial aspect of this preparation is ensuring that raw tapes do not form during the process [30].

The focus in the development of inorganic non-metal microneedles is to enhance their biocompatibility and reduce brittleness [31,32]. Current research is exploring the incorporation of hybrid materials to improve tissue interaction while maintaining mechanical strength [33,34].

2.2.2. Metals

Metal MNs include stainless steel, titanium, and aluminum. Stainless steel is commonly used in metal MNs. The surface of stainless steel MNs can be coated with a porous polymer to improve the drug delivery rate [35]. In addition, aluminum MNs can improve drug loading and mechanical properties by incorporating a dense network of needle-like nanotube film channels covering a large surface area [36]. Some metals are conductive, making them suitable for biosensing applications in addition to drug delivery [37].

The issue of metal toxicity is an objective concern, but it has not been thoroughly documented to date. In some patients, metals may also provoke immune or allergic reactions, necessitating careful selection of materials and surface coatings [38]. Furthermore, when applying to biosensors, special consideration must be given to ensuring a stable power supply, maintaining a sterile testing environment, and supporting batch production capabilities, especially in low-resource settings.

Research on metal microneedles aims to address existing safety issues by exploring different metal compositions. Additionally, it seeks to resolve challenges related to the complexity and porosity of the metal fabrication process.

2.2.3. Polymers

Polymers have gained popularity as the primary materials for creating MNs due to their ease of formability, quick processing cycle, and low cost. Some common polymer materials used for this purpose include polycarbonate (PC), polyvinylpyrrolidone (PVP), polylactide (PLA), acrylate, hydrogels, polyvinylalcohol (PVA), polycaprolactone (PLC), carboxymethylcellulose (CMC), and cellulose acetate phthalate (CAP) [18]. These polymers possess distinct characteristics and find applications in the field of biomedicine, particularly in the fabrication of MNs. They serve various purposes, including drug delivery and biosensing. Polymers such as PVP, PLA, PCL, Acrylat, and CMC are commonly employed for drug delivery purposes [39–42]. On the other hand, polymers like PC, Acrylat, CAP, and PVA find their utility in biosensing applications [43–46].

Polymers generally offer good biocompatibility, reducing the risk of adverse tissue reactions [47]. Additionally, since microneedles made from polymers dissolve in the skin, there is no need for needle removal, thereby minimizing the risk of needle injury and environmental contamination. The degradability of polymers allows for the design of microneedles that release drugs over a specified time frame, providing a continuous, controlled release that can complement oral medications and address issues of low utilization [48].

Polymer materials are receiving increasing attention due to their excellent biocompatibility, mechanical properties, low cost, and biodegradability. Currently, manufacturing technologies such as lithography, replication molding, 3D printing and micromachining have all been applied to polymer microneedles, becoming a popular choice for real-time detection and drug delivery patches. In the process of developing soluble or degradable microneedles, the main goal is to enhance its mechanical strength to increase permeability without affecting the dissolution rate. To this end, researchers are exploring advances in polymer chemistry and formulation to achieve an optimal balance between structural strength and dissolution properties.

3. Mechanistic basis of microneedle function in drug delivery

MNs interact with biological tissues primarily by creating microscale conduits through the stratum corneum, the outermost skin barrier, thereby allowing direct access to the viable epidermis and dermis without stimulating pain receptors [10]. Once inserted, MNs facilitate rapid diffusion of therapeutics into capillary-rich dermal layers, significantly enhancing systemic absorption and bypassing hepatic first-pass metabolism.

In the case of dissolvable MNs, the drug is embedded within a biodegradable polymer matrix that dissolves or swells in response to interstitial fluid. This enables time-controlled release of encapsulated agents, prolonging local drug exposure and improving bioavailability [49]. The release kinetics can be precisely adjusted by modifying polymer composition, molecular weight, and cross-linking density, offering flexibility in matching therapeutic demands of different sports injury types.

Beyond passive release, MN systems have evolved to incorporate stimuli-responsive carriers, which can respond to environmental cues such as pH, reactive oxygen species (ROS), temperature, or enzyme activity—conditions often present in injured or inflamed tissues [50]. For example, ROS-sensitive linkers enable drug release specifically at sites of oxidative stress, while pH-responsive systems enhance delivery to acidic, inflamed regions. These smart materials improve drug localization and therapeutic precision.

From an immunological perspective, MNs bypass antigen-presenting cell-deficient superficial skin layers and deliver bioactive agents into dermal regions rich in Langerhans cells and dendritic cells [51]. This targeted deposition may enhance immune recognition, cytokine signaling, and the effectiveness of immunomodulatory treatments, including exosome therapy or peptide-based drugs aimed at tissue regeneration.

Moreover, MNs have shown the ability to modulate the inflammatory microenvironment, such as promoting macrophage polarization from the M1 to the M2 phenotype, thereby facilitating resolution of inflammation and tissue repair. This is particularly relevant for sports injuries, where excessive inflammation can impede recovery. MN-mediated delivery of growth factors, extracellular vesicles (EVs), or small RNAs can further promote angiogenesis, reduce fibrosis, and restore extracellular matrix architecture.

Therefore, MNs not only function as minimally invasive delivery tools but also act as bioactive interfaces that influence pharmacokinetics, immune dynamics, and regenerative responses in a targeted and controlled manner. Compared to conventional drug delivery routes, MNs offer multiple advantages: they avoid hepatic first-pass metabolism typical of oral administration, eliminate needle-associated pain and infection risks of subcutaneous injections, and overcome the low permeability limitations of standard transdermal patches. Studies have shown that MN-mediated delivery can enhance drug absorption by 2–10-fold and reduce therapeutic onset time significantly, particularly for hydrophilic and macromolecular agents poorly absorbed via passive transdermal routes (Table 1).

4. The application prospect of microneedles in sports injuries

4.1. Muscle or tendon

During sports activities, muscle injuries are common, ranging from strains, tears, and ruptures to conditions like intramuscular tendon injuries, compartment syndrome, and tendinopathy [52]. The significance of post-injury treatment in sports is irrefutable. Targeted and immediate post-injury treatment could prevent secondary tissue damage, promoting efficient healing, and reducing the risk of chronic dysfunction, which is essential for rapid and safe return to sports [53–57]. Given the constraints and adverse effects of oral medications and conventional transdermal delivery methods, the MNs demonstrate potential benefits [9].

The treatment principles for muscle or tendon injuries primarily aim to decrease the inflammatory response, prevent muscle fibrosis, and enhance muscle repair [58,59]. For the control of local muscle or tendon inflammation after sports injury, MNs can not only be combined with various drugs for drug delivery, but also can be combined with biological materials such as exosomes for treatment (Figure 2A). Liu et al. [60] proposed a strategy for circumventing certain exosome limitations by utilizing nitrogen oxide nanomotors to propel exosome-loaded MNs to the site of injury for the treatment of Achilles tendinitis. This innovative approach effectively suppresses inflammation in Achilles tendinitis, stimulates tenocyte proliferation, elevates type I collagen expression, and prevents extracellular matrix degradation. Shabbir et al. [61] developed self-dissolving MNs for percutaneous delivery to enhance the solubility of Diacerein using a solid dispersion gel, and illustrated the anti-inflammatory efficacy and safety of this delivery system. To enhance muscle repair, Zhang et al. [62] utilized carbonized wormwood and prostaglandin E2 to create soluble MNs for promoting skeletal muscle repair. Furthermore, in cases where growth factors are insufficient during the repair process, preparations can be made loaded with suitable quantities of growth factors to stimulate endogenous repair [63]. Additionally, Liu et al. [64] reported that the MN patch infused with platelet-derived growth factor can markedly enhance tendon healing quality, stimulate angiogenesis, and encourage cell proliferation through the activation of the p38/cyclin D1 signaling pathway.

Figure 2.

The application prospect of microneedles in sports injuries. A. Microneedles for muscle or tendon treatment [60,62]: Copyright 2021, RSC and Copyright 2021, ACS. B. Microneedles for bone or cartilage treatment [70]: Copyright 2023, Elsevier. C. Microneedles for ligament or joint capsule treatment [78]: Copyright 2022, Wiley. D. Microneedles for superficial tissues or skin treatment [92]: Copyright 2024, Elsevier. E. Microneedles for nerve treatment [106]: Copyright 2022, ACS.

When the muscle cannot repair itself due to volumetric muscle loss, cell or tissue engineering can offer a solution [63]. A promising approach involves utilizing MNs loaded with cells for cell therapy [65]. Chang et al. [66] introduced cryomicroneedles (cryoMNs) designed to pack and transport live cells through the skin for transdermal cell therapy. They fabricated these cryoMNs through a process involving freezing media and embedding cells within a predetermined mold, enabling easy skin penetration and delivery of live cells. Moreover, frozen microneedles can be combined with classical sports injury management principles (Protection, Rest, Ice, Compression, and Elevation; PRICE principle). Essentially, cryoMNs offer an alternative to cold therapy by facilitating the targeted administration of drugs or biomaterials at the affected area. This strategy can effectively regulate inflammation and alleviate pain and swelling. The integration of cryoMNs technology with the PRICE principle holds great promise for a variety of applications in sports injuries.

4.2. Bone or cartilage

With regard to bone or cartilage lesions, sports injuries usually consist of fractures, bone marrow edema, periostitis, meniscal, articular cartilage injuries, post-traumatic osteoarthritis, and joint impingement, are usually caused by traumatic injury mechanisms, unfortunately leading to chronic bone and cartilage degeneration and pathology in most cases. For such patients, whether or not they undergo surgical intervention after injury, drug adjuvant therapy is essential [67]. MNs show significant potential for drug delivery in these cases due to their high delivery efficiency, simplicity, cost-effectiveness, acceptance, and safety (Figure 2B) [68].

Although established applications are mainly for chronic diseases such as rheumatoid arthritis, positive findings and similar routes of administration offer a positive outlook. Yu et al. [69] developed a layered dissolving MN system tailored to deliver the immunosuppressant tacrolimus and the anti-inflammatory drug diclofenac simultaneously to achieve simultaneous relief of skin and joint damage in patients with psoriatic arthritis. In addition, Lin et al. [70] employed degradable biopolymer MN patches to administer neutrophil membrane-encapsulated NSAIDs for managing rheumatoid arthritis, addressing the constraints of NSAIDs. Such methodologies suggest MN delivery systems and precise interventions for bone diseases resulting from sports-related injuries. However, MNs encounter challenges like limited permeability, especially in densely packed tissues like bone and cartilage. To address the limitation of MNs being limited to shallow tissue targeting and lacking the necessary hardness for penetrating hard tissue barriers like cartilage, Lin et al. [71] developed the innovative ‘hydrogel-Chinese acupuncture’ system. This system leverages acupuncture advantages to breach the cartilage barrier with minimal invasiveness and high precision. By utilizing a screw-thread structure needle for penetration and rotation, the hydrogel can be accurately placed in the subchondral bone, enabling precise lesion targeting for treatment. A phase I trial by Miller et al. [72] demonstrated the safety and local tolerability of diclofenac MN patches in healthy volunteers, while another clinical investigation by Lewiecki et al. [73] reported encouraging outcomes using MN-based drug delivery to treat bone metabolic disorders. These early clinical findings suggest that MN delivery systems may be safely applied and potentially beneficial for bone diseases resulting from sports-related injuries.

In addition to drug-loaded MNs, the utilization of growth factor-based biologics or stem cell-based hydrogel is crucial. For example, Wang et al. [74] employed a multifunctional hydrogel containing osteogenic-inducing dental pulp stem cell-derived EVs to enhance bone growth. Similarly, Ding et al. [75] demonstrated the promotion of osteochondral regeneration through apoptotic EVs derived from hypoxia-pretreated mesenchymal stem cells (MSCs) within a modified gelatin hydrogel. Additionally, Han et al.’s [76] recent study has notably enhanced the bioavailability and therapeutic efficacy of MN-administered drugs by mimicking the natural secretion rhythm of growth hormone. This investigation integrated a ‘burst release’ mechanism with several ‘delayed release’ modules to facilitate programmed drug delivery. When compared to daily subcutaneous injections, this patch exhibited superior effectiveness in promoting longitudinal bone growth and improving bone quality. The bone length in healthy rats and growth hormone gene knockout mice increased by approximately 10 mm and 5 mm, respectively.

4.3. Ligament or joint capsule

In sports, injuries to ligaments or joint capsules typically involve partial or complete tears of ligament, damage to non-specific ligaments and joint capsules (joint dislocations or subluxations). Surgical treatment is typically necessary for ligament repair or joint realignment in the case of these injuries. It is important to note that medical or other therapies – such as physical therapy, pharmacological treatment, regenerative approaches, and supportive interventions – are needed to promote recovery of these injuries even after surgical intervention [77]. These complementary treatments play a crucial role in enhancing tendon-bone integration, preventing fibrosis, and accelerating the rehabilitation process. MNs can overcome the skin barrier to deliver drugs, growth factors or other therapeutic substances directly to the damaged area in a minimally invasive manner, thereby promoting the healing process of the injury. Nevertheless, the direct utilization of microneedles for these illnesses is currently lacking (Figure 2C) [78]. It is worth noting that the potential application of MNs in such conditions is promising due to there being less fat, muscle and other soft tissue in these parts.

Ligament injuries, such as the anterior cruciate ligament (ACL), are commonly involved in sports injuries [79]. Once rupture occurs, surgical reconstruction is necessary. A challenge in the recovery process post-surgical reconstruction is the tendency for the tendon bone healing at the attachment point to form scar tissue instead of transitional tissue, often resulting in eventual failure [80]. The absence of a structured gradient characteristic and collagen fiber alignment in scar tissue compared to the tendon–bone interface is a significant factor contributing to the formation of fibrovascular scars with poor biomechanical properties, leading to suboptimal interfaces and an elevated risk of injury [81]. Regenerating tendon–bone interfaces poses a greater challenge than interosseous healing. A recent review indicates the potential of exosomes in facilitating the paracrine mechanism of MSCs to enhance tendon–bone healing [82]. MNs, as a viable subcutaneous delivery system, offer a promising approach for delivering exosomes as a therapeutic intervention. Cui et al. [83] discovered that exosomal miR-21-5p originating from bone marrow macrophages directly targeted Smad7, thereby triggering fibrogenesis activation in tenocytes. Additionally, Wu et al. [84] demonstrated that exosomal miR-21-5p could enhance the tendon-osseointegration process and enhance the maximum destructive load by diminishing Smad7 expression levels in a rat model of ACL reconstruction. The administration of these exosomes via MNs exhibits promising prospects.

Following a direct injury to the soft tissues surrounding a joint or the joint capsule itself, joint immobilization is commonly utilized to aid in recovery. Nevertheless, this approach can result in adverse effects like joint contractures and post-mobilization inflammation [85]. Treating joint capsule injuries is crucial, as excessive inflammation in the joint capsule can escalate to osteoarthritis [86]. The unique anatomical characteristics of the joint, characterized by less soft tissue surrounding it, enhance the efficacy of localized drug delivery using MNs. In a related development, Li et al. [87] introduced a Kirigami micro-nanogenerator based on spider silk that exhibits remarkable mechanical strength and flexibility. This innovative patch is capable of effectively penetrating the skin while accommodating the intricate movements of joints. This study presents a holistic approach to joint management. In a recent investigation, Zhang et al. [88] explored the impact of macrophage migration inhibitory factor inhibitors on joint capsule inflammation and fibrosis. Their findings demonstrated a noteworthy reduction in TGF-β₁ production, thereby alleviating symptoms associated with joint capsule inflammation and fibrosis. This research offers valuable insights into the underlying mechanisms of inflammatory joint diseases and their treatment. Concurrently, Li et al. [89] studied the effects of lentivirus-mediated ERK2 siRNA on the progression of joint capsule fibrosis and contracture. Their intervention successfully mitigated joint capsule fibrosis and slowed the advancement of contracture. These discoveries present a potential avenue for the advancement of MN therapy and introduce novel perspectives and strategies for managing such conditions.

4.4. Superficial tissues or skin

During exercise, superficial tissue and skin injuries are primarily caused by falls or participating in contact sports. These injuries can include bruises, abrasions, vascular damage, and lacerations. While certain research on microneedles has suggested effective methods for enhancing wound healing [90], it appears that MN therapy may not be essential for common sports-related injuries. However, it is important to pay special attention to injuries that occur in patients with chronic diseases that affect wound healing, such as diabetes cancer, or other diseases [91].

The MNs in the treatment of diabetic wounds offers significant therapeutic benefits by employing minimally invasive drug delivery systems (Figure 2D) [92]. These had a less intrusive, allowing for precise and targeted administration of a wide range of therapeutic substances. For example, Guan et al. [93] developed multifunctional MNs by incorporating Prussian blue nanozymes and vascular endothelial growth factor at the tip, while including Polymyxin at the base. This combination resulted in antioxidant, proangiogenic, and antibacterial properties. On the other hand, Zhao et al. [94] created separable MNs that utilized photosynthesis to generate oxygen, aiding in the healing of diabetic wounds. The experiments conducted on diabetic mice demonstrated that these MNs promoted cell proliferation, migration, and angiogenesis, effectively enhancing wound healing. Furthermore, Yuan and colleagues [95] demonstrated that an MN patch containing GelMA/PEGDA loaded with exosomes derived from human umbilical vein endothelial cells and Tazarotene facilitated cell migration and angiogenesis, offering a promising strategy for addressing diabetic wounds. Overall, these versatile MNs offer a promising therapeutic approach for accelerating the healing of diabetic wounds.

Although most superficial tissue and skin injuries during sports do not require much intervention, avoiding the potential harm caused by abnormal wound healing is still an important research direction [96]. In wound management, the presence of a wound scab can impede the absorption of drugs and potentially undermine the effectiveness of treatment. However, MNs can offer a solution to this issue by enhancing the absorption of drugs and ensuring proper adhesion [97]. Additionally, MNs can be designed to optimize the material and structure of the patch, leading to improved early wound tissue adhesion and hemostasis [98,99]. The application of MNs in wound management for sports injuries has the potential to expedite the return of athletes to the games. By understanding the various stages of wound healing, it is possible to develop MN systems tailored for detecting wound conditions and providing intelligent drug delivery [100].

4.5. Nervous

In the process of sports, nerve injury is a more serious injury type, which mainly includes concussion and various forms of brain injury, spinal cord injury, and peripheral nerve injury. Sports-related concussions can initiate a series of neurotransmitter and metabolic reactions that may lead to axonal injury, alterations in blood flow, and brain inflammation [101].

Following thorough evaluation and care, mild concussions do not typically require pharmacological intervention [101]. In cases of cerebral trauma with organic damage, it is imperative to consider surgical or medicinal interventions. Chiang et al. [102] utilized wireless charging gold yarn-dynamos for neurotherapy in the traumatic brain injury. Through endogenous signals (nitric oxide and electrons), this approach significantly promoted the differentiation and growth of neural stem cell synapses, while inhibiting inflammation, angiogenesis, and neural interference in traumatic brain injury. Apart from traumatic brain injury, Cerebral edema, a harmful outcome following brain injuries, involves the abnormal accumulation of fluid within the brain tissues, typically categorized as vasogenic or cytotoxic edema [103]. While there is currently a lack of research on MN applications for addressing brain edema, the potential of MNs to penetrate the blood–brain barrier presents promising opportunities (Figure 2E). For instance, Wang et al. [104] devised a silk fibroin MN patch capable of bypassing the blood–brain barrier to administer multiple drugs at the glioblastoma site for effective combination therapy. Similarly, Li et al. [105] developed a hybrid delivery system incorporating nanocarriers and MN technology to explore the feasibility of transdermal drug delivery to the brain for treating neurological disorders. Furthermore, Chiang et al. [102] integrated a high-frequency magnetic field-responsive nitric oxide-release gold yarn-dynamos into silk-based MNs for implantation in vivo. They induced nitric oxide release and electrical stimulation through high-frequency magnetic fields to enhance the differentiation and growth of neural stem cell synapses.

The current focus of research in the field of spinal cord injury (SCI) and peripheral nerve injury revolves around enhancing repair mechanisms and alleviating pain. Han et al. [106] developed a novel approach for spinal cord repair by creating a 3D-cultured mesenchymal stem cell (MSC)-derived exosome/hydrogel hybrid MN patch. The patch enables continuous exosome release at the injury site, offering a reliable, convenient, and effective treatment option for spinal cord injuries. Zhai et al. [107] engineered a transdural MN patch utilizing a β-cyclodextrin metal-organic framework to facilitate the controlled release of methylprednisolone sodium succinate for targeted drug delivery post-spinal cord injury. Furthermore, Fang et al. [108] designed a porous MN patch that sustains the release of EVs in an animal model of compressive spinal cord injury. This patch mitigated the formation of cavities and scar tissue, boosted angiogenesis, and enhanced the survival of neighboring tissues and nerve fibers. Recently, Chen et al. [109] have developed a photothermal-responsive MN patch that is activated by near-infrared (NIR) light. This innovative patch incorporates gold@polyphenol nanospheres to facilitate controlled drug release. The NIR-responsive MNs offers several benefits, including the efficient elimination of reactive oxygen species, enhancement of mitochondrial autophagy, restoration of redox balance, and a reduction in neuronal apoptosis.

For analgesia, Xie et al. [110] developed a novel MN patch for analgesia to manage neuropathic pain by delivering a specific CGRP antagonist peptide through the skin. This method effectively alleviates neuropathic pain without impacting normal sensory and motor functions, demonstrating both high safety and efficacy. In another study, Song et al. [111] combined borneol-modified liposomes with exosomes from MSCs loaded with Ziconotideto create MNs for enhanced delivery of Ziconotide across the blood–brain barrier. These MNs demonstrated significant analgesic effects in various pain models, offering a safe and efficient strategy for chronic pain treatment. Zhang et al. [112] developed a dissolving MN patch for peripheral drug delivery aimed at managing neuropathic pain. This innovative patch exhibited notable analgesic properties and was capable of providing sustained drug release at the site of application for up to 48 h, effectively mitigating pain while minimizing common systemic side effects such as dizziness and drowsiness. Similarly, Han et al. [113] created a NIR light-responsive MN patch for the treatment of neuropathic pain. In a mouse model, the most significant pain relief was recorded within one hour following a single exposure to NIR light, with effects lasting up to six hours. Furthermore, during subsequent pain episodes, the MN patch maintained comparable therapeutic efficacy as observed during the initial light exposure.

5. Microneedle-based biosensing for sports medical supervision

In sports medical supervision, it is crucial to focus on preventing, diagnosing, and treating sports-related conditions. Blood serves a critical role in disease identification, monitoring progression, and evaluating metabolic processes. Nevertheless, conventional blood extraction methods pose challenges such as potential tissue damage, infection risks, and pain [114]. Recently, wearable sensing technology utilizing MNs has emerged as a promising solution to these shortcomings [115]. These devices allow for the capture, identification, onsite detection, and continuous monitoring of specific biomarkers in skin interstitial fluid under the skin [116]. While skin interstitial fluid should not be considered a direct replacement for blood analysis, the utilization of wearable sensors utilizing MNs presents a cost-effective and continuous monitoring solution with improved convenience [117]. In this review, we mainly included the monitoring of exercise-related indicators [118–124] and drug monitoring [125,126] (Table 2). This innovative approach opens up possibilities for advancing medical oversight in the field of sports.

Table 2.

Microneedles for different sports medical supervision.

Target analyte	Microneedle type	MN dimension	Sensing method	High sensitivity	Purpose	Literature
Lactate	Solid and polymers and metals	–	Electrochemical detection (chronoamperometry)	43.96 μA mM⁻¹ cm⁻²	Real-time lactate monitoring for use in sports medicine and treatment	Reza et al. [128]
Urea	Hollow and polymers and metals	700–720 μm	Electrochemical sensing (potentiometry)	2.5 mV/mM	Muscle breakdown and hydration status	Dervisevic et al. [129]
Glucose, pH	Hollow and polymers	200 μm	Electrochemical sensing (amperometry, potentiometry)	–	Continuous, minimally invasive sampling	Abbasiasl et al. [127]
Cortisol	Solid and polymers and metals	600 μm	Electrochemical sensing (differential pulse voltammetry)	0.17 nM	Stress assessment and circadian rhythm monitoring	Jing et al. [136]
Cortisol, dopamine	Soluble and polymers	1200 μm	Distance-based paper analytical device	0.25 µg/mL(cortisol)+ 1.0 ng/mL(dopamine)	Mood, fatigue, and recovery signal tracking	Dos Santos et al. [137]
Lactate, pH, sodium	Solid and polymers	50 μm	Electrochemical sensing (amperometric, potentiometric, thermistor)	–	Assessed human health and performance	Anastasova et al. [118]
Metabolites, lipids	–	–	Mass spectrometry	225 Metabolites + 1, 118 lipids, <10 ppm	Outdoor sports training and performance monitoring	Cendali et al. [119]
Lactate, glucose	Solid and polymers	1000 μm	Electrochemical biosensing (cyclic voltammetry and chronoamperometry)	lactate (797.4 ± 38.1 μA cm⁻² mM⁻¹) and glucose (405.2 ± 24.1 μA cm⁻² mM⁻¹)	Simultaneous, continuous, and minimally invasive monitoring	Bollella et al. [140]
Lactate	Solid and metals	1000 μm	Electrochemical biosensing (cyclic voltammetry)	–	Analysing lactate response to exercise, assessing exercise performance and training exercise intensity	Chien et al. [121]
Pressure sensing	Solid and metals	275–856 μm	Piezocapacitive	0.159 kPa⁻¹	Low-cost, wide range pressure sensing, high sensitivity, and tunable sensing performance	Asghar et al. [122]
pH	Solid and polymers	650 μm	Electrochemical detection (potentiometric method)	53.60 mV	Timely intervention and better management	Kuang et al. [123]
Subcutaneous oxygen	Solid and metals	25000 μm	Electrochemical biosensing (amperometry)	0.3817 μA/mmHg	Warning about the hypoxia status of the human body	Liu et al. [124]
Fentanyl, morphine, norfentanyl, Organophosphate compounds	Hollow and metals	–	Electrochemical biosensing (square wave voltammetry, cyclic square wave voltammetry)	50 nM	Continuous, real-time routine detection during the race	Mishra et al. [125]
Dopamine, epinephrine, and norepinephrine	Solid and metals	1000 μm	Electrochemical sensor	100 nM	Continuous, real-time routine detection during the race	Tortolini et al. [126]

5.1. Metabolites monitoring

During exercise training, various metabolites serve as essential indicators of body condition, including lactate, urea, testosterone, cortisol, and creatine kinase. The emergence of MN technology presents exciting possibilities for wearable biosensors by integrating them with MNs. Abbasiasl et al. [127] developed a touch-activated wearable device that incorporates hollow microneedles for continual extraction and monitoring of subcutaneous interstitial fluid (Figure 3A). This device enables painless and user-friendly retrieval of subcutaneous interstitial fluid, with the platform utilizing finger manipulation to create and sustain the necessary vacuum pressure for fluid collection.

Figure 3.

The application of microneedle-based biosensing for sports medical supervision. A. The HMN (hollow microneedle)-based wearable device for on-metabolites monitoring. (i: device mounted on the human arm; ii: different parts of the VIES (vacuum-integrated ISF extraction and sensing) system; iii: Continuous monitoring of vacuum pressure and ISF (interstitial fluid) glucose and pH levels [127]: Copyright 2023, Wiley. Microneedle sensor array for detecting opioids and nerve agents. B. Doping monitoring on a wearable Microneedle sensor array. (i:Microneedle electrodes for square wave voltammetric detection of the fentanyl and nerve agent targets, respectively; ii: Sensing device capable of continuously monitoring fentanyl down to the nanomolar level through a nanomaterial-based multilayered surface architecture). Reproduced with permission [125]: Copyright 2020, ACS.

Reza and colleagues [128] have innovated a functionalized polymer MN electrode incorporating reduced graphene and platinum nanoparticles for continuous and thorough monitoring of lactate levels in interstitial fluid. This electrode demonstrates exceptional linearity, sensitivity, response time, and durability, making it well-suited for real-time lactate monitoring with potential applications in sports medicine and therapy. On the other hand, Dervisevic et al. [129] have introduced a wearable MN patch for electrochemical monitoring of urea in subcutaneous fluids. Leveraging advancements in micro and nanomanufacturing techniques, MNs with conductive concave microcavities have been developed to enable precise monitoring of urea concentrations in subcutaneous fluids. Overall, the percutaneous sensing system utilizing MNs shows promise for practical applications in sports medicine and medical monitoring, offering a valuable avenue for further research.

5.2. Doping monitoring

The persistent issue of performance-enhancing drug use in modern sports poses significant concerns [130]. Doping detection in sports traditionally involves the identification, characterization, and utilization of urine metabolites as targets [131]. This aids in identifying the origin of the substance (natural or exogenous) and estimating the timing and dosage of drug use. Recently, there has been a suggestion to use interstitial fluid for in vivo drug analysis [117]. Mishra et al. [125] have introduced a wearable MN sensor array for ongoing monitoring of opioids and nerve agents, offering high sensitivity, selectivity, and stability (Figure 3B). This innovation represents the first capable of continuous monitoring of fentanyl levels at the nanomole scale, with successful validation for morphine and norfentanyl screening as well. Furthermore, Tortolini and colleagues [126] have engineered a nanomaterial-based electrochemical sensor using MNs with nanopore gold for the immediate detection of catecholamines. This sensor demonstrates remarkable sensitivity, stability, and rapid response time, along with an exceptionally low detection limit. Despite the limited research on MNs in drug analysis, particularly in the context of doping surveillance, this avenue of investigation shows promise for substantial growth and advancement in relevant disciplines in the foreseeable future.

6. Application suggestions of microneedles in sports scenarios and special needs

MNs offer significant advantages in sports injury management due to their convenience and versatility, making them applicable across various athletic scenarios. Particularly in intermittent sports like basketball and football, the design of soluble MN patches with a drug release time of under 10 s can swiftly address athletes’ needs during game stoppages. It is essential to select sweat-resistant composite materials, such as sodium alginate [132], which exhibits excellent water adhesion, ensuring the MNs remain effective during high-intensity activities.

In high-altitude sports, the development of slow-release MNs containing acetazolamide [133] can effectively mitigate the risk of cerebral edema in mountaineers, thereby enhancing athlete safety. Additionally, in the high-temperature environment, MNs can monitor electrolyte levels, providing timely alerts regarding dehydration risks [134]. MNs also can facilitate personalized drug dosage adjustments, such as formulating a reduced ibuprofen dose for individuals with CYP2C9 poor metabolism [135], allowing for precise management of metabolic variations.

MNs equipped with sensing capabilities can continuously monitor biomarkers like cortisol and dopamine [136,137] and a therapeutic MNs loaded with melatonin can be designed to trigger when the relevant indicators reach a threshold to promote the sleep recovery of athletes. Moreover, cryoMNs [66] can be delivered in combination with anti-inflammatory drugs to provide a composite functional solution to the traditional ice application.

7. Limitations

Despite it being promising, the utilization of MNs in sports injury treatment remains limitation that hinder clinical translation.

Firstly, combining MNs with conventional drugs or biologics—such as growth factors, EVs, and stem cells—requires careful optimization to ensure delivery efficiency and mechanical integrity. These biomaterials present formulation challenges due to their structural complexity, sensitivity to environmental conditions, and high production costs, all of which affect stability, scalability, and therapeutic efficacy. Secondly, cost-effectiveness remains a concern, particularly for repeated or large-scale applications in athletic populations, where economic feasibility is crucial for widespread adoption. Third, biosensing applications of MNs also face practical constraints. Extended skin contact may cause local discomfort or inflammatory responses, while physiological fluctuations during exercise (e.g. perspiration, pH changes, and blood flow variability) may compromise sensor accuracy. These issues collectively contribute to regulatory uncertainties related to microneedles—such as their classification as medical devices or drug–device combination products—which in turn hinder their approval and widespread clinical adoption [138].

Moreover, existing clinical research on MNs is primarily limited to general medical contexts, with scarce evidence focusing on their effects in sports-specific conditions. There is a lack of high-quality studies assessing critical outcomes such as athletic performance recovery, functional joint stability, or return-to-play timelines, which are essential for real-world adoption in sports medicine.

8. Conclusions

MN therapy shows significant promise in treating and monitoring sports injuries as a novel treatment approach. By integrating MNs with existing therapies, they can significantly enhance tissue repair, and optimize drug efficacy. As technology advances, MN therapy is poised to become increasingly vital in sports medicine, offering more efficient and convenient treatment options for both athletes and non-athletes.

Funding Statement

This work was supported by grants from the Sichuan Science and Technology Program (2022YFS0609); the Scientific Research Cultivation Project of The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University (2022-CXTD-08); the Integrated traditional Chinese and Western Medicine Special Project of Southwest Medical University (Optimizing Basic Disciplines Plan 2023ZYYJ03).

Disclosure statement

All authors have declared no conflict of interest.

Data availability statement

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