From Promise to Practice: Recent Growth in 30 Years of Tissue Engineering Commercialization

Abstract

This perspective, marking the 30th anniversary of the Tissue Engineering journal, discusses the exciting trends in the global commercialization of tissue engineering technology. Within a historical context, we present an evolution of challenges and a discussion of the last 5 years of global commercial successes and emerging market trends, highlighting the continued expansion of the field in the northeastern United States. This leads to an overview of the last 5 years’ progress in clinical trials for tissue-engineered therapeutics, including an analysis of trends in success and failure. Finally, we provide a broad overview of preclinical research and a perspective on where the state-of-the-art lies on the horizon.

Impact Statement

This perspective, marking the 30th anniversary of the Tissue Engineering journal, discusses the exciting trends in the global commercialization of tissue engineering technology.

Introduction: A Historical Perspective

In the mid-20th century surgical advances made organ allotransplantation possible for kidneys, liver, lungs, hearts, and other major organs. ^{1 –4} These strides represented a considerable bound in modern medicine, one where collaborative effort between physicians, surgeons, and scientists partially mitigated challenges with transplant rejection that plagued progress. In the present day, the success of allotransplantations has continued to prevent deaths and prolong lives globally.

Unfortunately, allotransplantation is an imperfect solution. Donor matching can prove challenging or impossible, and transplant recipients who avoid rejection still require lifelong reliance on immunosuppressants. ^5,6 Furthermore, allotransplantation remains entirely dependent on qualifying recently deceased or charitable living donors, the deficit of which expands annually. ^7,8 By the early 1990s, the recognition of this new class of challenges had set the stage for the birth of a new field, aiming to pioneer the development of autologously sourced and manufactured tissues. Autologous cell sources would resolve the need for immunosuppression, and manufacturing organs could alleviate organ supply shortages. In this era, clinical trials of autologous chondrocyte implantation had just generated positive results on follow-up, ⁹ and a patient with Poland’s syndrome received the first engineered implant—a cell-laden synthetic polymer sternum. ¹⁰

Fittingly, researchers began to pursue ‘tissue engineering’; ¹¹ many early investigations are attributable to the research partnership of Robert Langer, an engineer at Massachusetts Institute of Technology, and Joseph P. Vacanti, a surgical physician at Boston Children’s Hospital. The two, alongside a global cohort of prominent researchers, were among the first to investigate the methods required to realize engineered tissue constructs. ¹² Their early and guiding definitions of the field defined it as an “interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue or whole organ function” (Fig. 1).

FIG. 1.

Three perspectives on the 30-year evolution of tissue engineering (A) Timeline of historical milestones in tissue engineering. (B) Tissue engineering paradigm incorporating the process of cell isolation from patient source; cell, material, or signal selection for the fabrication of tissue engineered construct; and maturation of the construct in vitro prior to implantation. (C) Volume of tissue engineering, biomaterials, and stem cell publications from 1994 to 2022 demonstrating parallel growth in the field. [data from pubmed.gov, PubMed database keyword search: tissue engineering, biomaterials, and stem cell, filtering for years 1994 to 2022].

However, despite the great promise of the field, progress to clinical translation has been slow, hindered by gaps in knowledge related to autologous stem cell harvest and directed differentiation to somatic cell phenotypes, difficulties in precise manufacturing of tissue constructs, and challenges with maintaining cellular viability and function in large tissue constructs. ¹³ –16 Irrespective of these fundamental biology and biomedical engineering gaps, the field has maintained a record of clinical advances alongside major preclinical achievements (Fig. 1a). ^{1 –4,9,10,17 –27} For example, in 2001, a 4-year-old girl received an engineered pulmonary artery that demonstrated impressive postoperative performance at a 7-month follow-up²². Only 5 years later came the discovery of stem cells with inducible pluripotency (iPSCs), ^23,24,28 which were used less than a decade later to fabricate a retinal sheet implanted in a woman with macular degeneration. ²⁷

Now, 30 years from its inception, the field of tissue engineering has several therapeutic products on the market for applications in the regeneration of articular cartilage, bone, and burn wounds. ^29,30 Furthermore, the field has evolved from its original definition and purpose, now encompassing ex-vivo tissue constructs that aim to recapitulate native tissue structure and function (Fig. 1b). These constructions are becoming increasingly popular as performance assessment platforms, so much so that they now play a role in regulatory approval of therapeutics beyond tissue engineering and regenerative medicine. These changes have arisen since the latest review on the tissue engineering industry. ³¹ In this study, we plan to discuss in detail the expansion of tissue engineering as an industry within the last five years of growth.

In this review, we discuss the following three key elements of the field of tissue engineering: 1) commercialized technology and approved therapeutics that have reached patients’ bedside, 2) ongoing clinical trials to investigate the safety and efficacy of therapies, and 3) preclinical directions at the industry and academic level. While discussing these topics, we aim to highlight key historical events in the last 30 years of tissue engineering and regenerative medicine, provide the reader with detailed discussions of the most contemporary trends in the field, and finally, predict the discipline’s overall future.

Methods

Herein we pursue an evolution of methodologies, choosing best practices from previous iterations of reviewing the tissue engineering discipline, including the first set of reviews by Lysaght. ^{31 –34}

Identification of potential tissue engineering companies

Potential tissue engineering companies were identified (Fig. 2) through the following: 1) abstraction from prior reviews, ^32,34,35 2) a PubMed search of peer-reviewed literature for abstracting companies listed in affiliation and conflict of interest statements, 3) the most current list of FDA-approved cellular & gene therapies, and 4) a ClinicalTrials.gov search for trials listing companies as sponsors or collaborators. We limited all database searches to results from 2019 to September 2023, such that we only include data since the last review. Specific documentation of search terms and data scope are described in the next section of the methods. We defined search terms based on previous reviews, in-laboratory discussions, and consultation with our university’s specialist librarian in bioengineering. The consolidated dataset consisted of 6,259 companies and was deduplicated and cleaned to remove names of individuals, hospitals, government agencies, universities, foundations, and trusts. The finalized list of potential TERM companies included 3,324 entries.

FIG. 2.

Methods for Identifying Active Tissue Engineering Companies. Tissue engineering companies were identified from author affiliations and conflict of interest statements in the last 5 years of PubMed searchable literature, listings of sponsors and collaborators of trials indexed by ClinicalTrials.gov, and FDA approved cell and gene therapies. An inclusion/exclusion criterion narrowed the list to currently active tissue engineering and regenerative medicine companies.

Companies were further classified by stage based on the stage of their leading product as commercial, clinical, or preclinical stage. Commercial products were defined as products that were commercially available to customers, clinical products were defined as potential products currently undergoing clinical trial investigation, and preclinical products were defined as products that are still in the in vitro or in vivo experimental testing phase. Furthermore, companies were categorized by their product sector as stem cell companies, biomaterial companies, or cells and biomaterial companies. Stem cell companies were defined as companies whose leading product used a cell therapeutic as its primary mode of action, biomaterial companies were defined as those whose leading product used a biomaterial or hydrogel technology as its primary mode of action, and cell and biomaterial companies were defined as companies whose leading product used a combination of a cell and biomaterial or hydrogel technology for therapeutic purposes. The authors acknowledge that these categorizations comprise company views at a snapshot in time which can evolve quickly as products change and are based on the author’s interpretation of openly available company information.

Search criteria

The PubMed literature search identified 2,180 publications from 2019 to 2023 that included the terms tissue engineer* or regenerative medicine, any of the terms compan*, LLC, or corporation within the author affiliations, or compan*, LLC, corporation, or owner* within the conflict-of-interest statements. The ClinicalTrials.gov database search identified 3,401 clinical trials from 2019 to 2023 that included any of the terms tissue engineering, regenerative medicine, stem cell, biomaterials, scaffold, hydrogel, or bioprinting; however, it excluded trials including the term cord.

FDA Approved Therapeutics: Consisted of the 32 approved therapeutics in the Cell & Gene Therapies category as of June 30th, 2023.

For analysis of publication volume in the field of tissue engineering a PubMed search was performed for publications from 1994 to 2022 using the keywords tissue engineering, biomaterials, and stem cells independently.

Inclusion–exclusion criteria

We identified a total of 3,324 potential tissue engineering companies through the described methods. We built upon criteria in prior reviews to narrow these companies to include only those performing tissue engineering and regenerative medicine. We defined a tissue engineering company as one that utilizes cells, biomaterials, and signals individually or together for recapitulating or regenerating native tissues. Specifically, we included cell and stem cell therapies, biomaterials, and scaffold or hydrogel technologies. We excluded companies performing gene therapies, chimeric antigen receptor T cell therapies, cord and stem cell blood banks or storage, drug-eluting stents, unmodified allo/xeno-transplantation, bone marrow therapies, classical orthopedic biomaterials, antibody therapies, and cosmetics. After exclusion of the inactive companies, we identified 347 international tissue engineering companies.

Financial data abstraction

We obtained relevant financial data on each of the 347 included companies through abstraction from the Mergent Intellect international business directory ³⁶ and from the United States Securities and Exchange Commission Form 10-K or 10-Q filings obtained through the Electronic Data Gathering, Analysis, and Retrieval (EDGAR) system. Finally, the cumulative sales from companies identified from the Mergent Intellect data abstracted for this review were compared with that reported in past iterations of the review. ^34,35

International Tissue Engineering Commercialization

Our investigations have identified 347 tissue engineering companies internationally, 87% being private companies (Table 1). Notably, our selection criteria are more conservative by exclusion of blood and tissue banks, which made up a substantial portion of all companies in past iterations of this review. ^34,35 Despite this, 347 companies represent a 71% growth in the number of companies since the figure was last reported by Jaklenec et al. in 2012 (Fig. 3b). ³⁵ Furthermore, an estimated quarter of these companies originated in the last five years, indicating healthy expansion of the field.

Table 1.

List of Identified Tissue Engineering Companies, Their Locations, Stages, Product Sectors, and Website Link

Company	Location	Stage	Ownership	Sector	Sales (USD)	Employees	Website
3-D matrix	Newton, MA	Commercial	Public	Cells and Biomaterials	$17,441,244	108	https://3dmatrix.com/us/
3DBio therapeutics	Long Island city, NY	Clinical trials	Private	Cells and Biomaterials	$410,137	4	https://3dbiocorp.com/
4D Biomaterials	Nottingham, England	Commercial	Private	Cells and Biomaterials	$1,816,584	9	https://4dbiomaterials.co.uk/
Accurate International Biotechnology Co	Guangzhou, China	Commercial	Private	Cells and Biomaterials	$182,612	4	https://en.bio-accurate.com/
Acell	Columbia, MD	Commercial	Private	Biomaterials	$100,794,336	438	https://marketing.integralife.com/acell
Acera Surgical	St. Louis, MO	Commercial	Private	Cells and Biomaterials	$4,875,411	41	https://acera-surgical.com/
Aesculap Biologics	Breinigsville, PA	Clinical Trials	Private	Cells and Biomaterials	$2,222,917	25	https://www.aesculapbiologics.com/
Akan Biosciences	Gaithersburg, MD	Clinical Trials	Private	Cells and Biomaterials	$102,915	2	https://akanbio.com/
Allevi	Philadelphia, PA	Commercial	Private	Biomaterials	$1,151,243	6	https://www.allevi3d.com/
AlloSource	Centennial, CO	Commercial	Private	Cells and Biomaterials	$155,893,092	160	https://allosource.org/
AMASA Therapeutics	Boston, MA	Preclinical	Private	Stem Cells			https://www.amasatx.com/
American CryoStem Corporation	Eatontown, NJ	Clinical Trials	Private	Stem Cells	$20,590	6	https://www.americancryostem.com/
Angiocrine Bioscience	San Diego, CA	Clinical Trials	Private	Stem Cells	$4,057,719	22	https://angiocrinebioscience.com/
Angiograft	Amherst, NY	Preclinical	Private	Biomaterials	$172,593	3	https://angio-graft.com/
Anika Therapeutics	Bredford, MA	Commercial	Public	Biomaterials	$156,236,000	277	https://anika.com/
Anterogen Co	Seoul, South Korea	Commercial	Private	Stem Cells	$4,930,068	42	http://anterogen.com/
AntiCancer	San Diego, CA	Preclinical	Private	Cells and Biomaterials	$4,271,708	29	http://www.anticancer.com/
APIE Therapeutics	Research Triangle Park, NC	Preclinical	Private	Stem Cells	$284,009	3	https://apie-therapeutics.com/
Appia Bio	Culver City, CA	Preclinical	Private	Stem Cells	$9,857,989	24	https://www.appiabio.com/
Aracari Biosciences	Irvine, CA	Commercial	Private	Cells and Biomaterials	$466,741	4	https://aracaribio.com/
Aran Biomedical	Galway, Ireland	Commercial	Private	Cells and Biomaterials	$14,847,137	10	https://www.aranbiomedical.com/
Aroa Biosurgery Limited	Auckland, New Zealand	Commercial	Private	Cells and Biomaterials	$14,344,650	150	https://aroa.com/
Arthro Kinetics	Germany	Commercial	Private	Biomaterials	$310,536	16	https://www.arthro-kinetics.com/
Artivion (formerly Cryolife)	Atlanta, GA	Commercial	Public	Biomaterials	$313,789,000	1,200	https://artivion.com
Asia Cell Therapeutics Co	Hong Kong SAR, China	Commercial	Private	Stem Cells			https://asiacelltherapy.com/
Aspect Biosystems	Vancouver, Canada	Commercial	Private	Cells and Biomaterials	$796,290	5	https://www.aspectbiosystems.com/
Astellas	Tokyo, Japan	Preclinical	Public	Stem Cells	$11,263,597,123	14,484	https://www.astellas.com/
Athersys	Cleveland, OH	Clinical Trials	Public	Stem Cells	$5,325,000	97	https://www.athersys.com/
Atreon Orthopedics	Dublin, OH	Commercial	Private	Cells and Biomaterials	$247,767	8	https://www.atreonortho.com/
Auto Tissue Berlin	Berlin, Germany	Commercial	Private	Cells and Biomaterials	$3,404,682	30	https://autotissue.de/
Avery Therapeutics	Tucson, AZ	Preclinical	Private	Cells and Biomaterials	$889,363	5	https://averythera.com/
Avita Medical	Santa Clarita, CA	Commercial	Private	Cells and Biomaterials	$34,421,000	114	https://ir.avitamedical.com/
Avobis Bio	Newark, DE	Clinical Trials	Private	Stem Cells	$100,267	6	https://www.avobisbio.com/
Axcelon Biopolymers	Canada	Commercial	Private	Biomaterials	$3,273,440	10	https://axcelonbp.com/
Axogen	Alachua, FL	Commercial	Public	Biomaterials	$138,584,000	199	https://ir.axogeninc.com/
Axolotl Biosciences	Victoria, Canada	Commercial	Private	Cells and Biomaterials	$1,433,322	9	https://www.axolotlbiosciences.com/
Axonova Medical	Philadelphia, PA	Preclinical	Private	Cells and Biomaterials	$29,465	1	https://axonovamed.com/
Baxter	Deerfield, IL	Commercial	Public	Biomaterials	$15,113,000,000	60,000	http://baxter.com
Baylx	Irvine, CA	Clinical Trials	Private	Stem Cells	$418,748	8	https://www.baylxinc.com/
Beike Biotechnology	China	Clinical Trials	Private	Stem Cells	$33,103,200	600	https://beikebiotech.com/
BellaSeno	Leipzig, Germany	Clinical Trials	Private	Cells and Biomaterials	$535,000	19	https://www.bellaseno.com/
BetaCell	Belgium	Preclinical	Private	Cells and Biomaterials	$20,027,840	70	https://www.beta-cell.com/
BHI Therapeutic Sciences	Hackensack, NJ	Clinical Trials	Private	Stem Cells	$256,338	8	https://bhisciences.com/
Bioactive Surfaces	Madrid, Spain	Commercial	Private	Cells and Biomaterials	$33,443	2	https://www.bioactivesurfaces.com/
BioAesthetics Corporation	Durham, NC	Commercial	Private	Cells and Biomaterials	$352,545	2	https://bio-aesthetics.com/
Biocardia	Sunnyvale, CA	Clinical Trials	Public	Stem Cells	$1,352,000	36	https://www.biocardia.com/
Biocomposites	England	Commercial	Private	Biomaterials	$51,994,519	88	https://biocomposites.com/
BIOFABICS Lda	Porto, Portugal	Commercial	Private	Cells and Biomaterials	$46	7	https://biofabics.com/
BioGend Therapeutics Co	Taipei, Taiwan	Commercial	Private	Cells and Biomaterials	$1,014,857	31	https://www.biogend.com/
BioIntegrate	New York, NY	Commercial	Private	Stem Cells	$76,543	6	https://biointegrate.com/
BioLife4D	Buffalo Grove, IL	Preclinical	Private	Cells and Biomaterials	$199,958	7	https://biolife4d.com/
BiomeSense	Chicago, IL	Commercial	Private	Cells and Biomaterials	$418,752	1	https://www.biomesense.com/
BioRestorative Therapies	Melville, NY	Clinical Trials	Public	Stem Cells	$119,800	10	https://www.biorestorative.com/
Biorez	Utica, NY	Commercial	Private	Cells and Biomaterials	$615,553	7	https://www.conmed.com/
Biorg	Winston-Salem, NC	Commercial	Private	Cells and Biomaterials	$258,977	7	https://www.biorg.com/
BioTissue AG	Miami, FL	Commercial	Private	Cells and Biomaterials	$38,430,099	270	https://biotissue.com/
Biotissue Technologies	Germany	Commercial	Private	Cells and Biomaterials	$316,000	7	https://biotissue.ch/
BioXcellerator	Antioquia, Colombia	Commercial	Private	Stem Cells	$97,505	42	https://www.bioxcellerator.com/
Blue Cell Therapeutics	Copenhagen, Denmark	Clinical Trials	Private	Stem Cells	$245,064	15	https://blue-cell.com/
BlueRock Therapeutics	Cambridge, MA	Clinical Trials	Private	Stem Cells	$26,120,907	168	https://www.bluerocktx.com/
Body Organ Biomedical Corporation	Taipei City, Taiwan	Commercial	Private	Cells and Biomaterials	$785,822	53	https://aeonastron.com/
Bonalive Biomaterials	Turku, Finland	Commercial	Private	Cells and Biomaterials	$4,452,431	44	https://www.bonalive.com/
Boston Sight	Needham, MA	Commercial	Private	Cells and Biomaterials	$8,192,679	45	https://www.bostonsight.org/
BrachyFoam	Charlottesville, VA	Commercial	Private	Cells and Biomaterials	$90,969	1	https://www.advaray.com/
Brainstorm Cell Therapeutics	New York City, NY	Clinical Trials	Public	Stem Cells		17	https://brainstorm-cell.com/
Brightlands Chemelot Campus B.V. L.F.	Geleen, Netherlands	Preclinical	Private	Cells and Biomaterials	$35,490	71	https://www.brightlands.com/
BTI Biotechnology Institute	Alava, Spain	Preclinical	Private	Biomaterials	$24,559,991	49	https://bti-biotechnologyinstitute.com/
CAM Bioceramics	Leiden, Netherlands	Commercial	Private	Biomaterials	$310,536	4	https://cambioceramics.com/
Capricor Therapeutics	San Diego, CA	Clinical Trials	Public	Stem Cells	$2,551,469	48	https://www.capricor.com
Cardioplant	Pensa, Russia	Commercial	Private	Biomaterials	$1,476,648	30	https://cardioplant.ru/en
Cell Reprogramming and Therapeutics	Wauwatosa, WI	Preclinical	Private	Stem Cells	$230,898	2	https://cellrtherapeutics.com/
Cell Therapy Sciences	Coventry, England	Commercial	Private	Stem Cells	$403,742	5	https://www.celltherapysciences.co.uk/
Cellatoz Therapeutics	Gyeonggi-do, Korea	Preclinical	Private	Stem Cells	$18,261,200	400	https://cellatozrx.com/
Cellatrix	St. Louis, MO	Commercial	Private	Cells and Biomaterials	$130,622	2	https://cellatrix.com/
Cellf Bio	Winston-Salem, NC	Clinical Trials	Private	Cells and Biomaterials	$283,242	3	http://www.cellfbio.com/
Cellfiber	Tokyo, Japan	Commercial	Private	Cells and Biomaterials	$510,727	16	https://cellfiber.jp/
CellGenix Technologie Transfer GmbH	Germany	Commercial	Private	Stem Cells	$11,024,028	142	https://cellgenix.com/
CellGro Technologies	Lincoln, NE	Commercial	Private	Cells and Biomaterials	$86,457	4	https://cellgrotechnologies.com/
CELLINK	Gothenburg, Sweden	Commercial	Private	Biomaterials	$5,197,902	45	https://www.cellink.com/
Cells for Cells	Santiago, Chile	Clinical Trials	Private	Cells and Biomaterials	$1,529,000	40	https://c4c.cl/
CellSeed	Tokyo, Japan	Commercial	Private	Cells and Biomaterials	$911,665	30	https://www.cellseed.com/
Cellular Logistics	Madison, WI	Commercial	Private	Stem Cells	$660,350	4	https://cellogistics.com/
Celluminova AB	Linköping, Sweden	Commercial	Private	Stem Cells		2	https://celluminova.se/
Cellus Medicina Regenerativa	Santiago, Chile	Clinical Trials	Private	Stem Cells	$542,000	7	https://www.cellus.cl/
CHA Biotech Co	Seongnam, South Korea	Clinical Trials	Private	Stem Cells	$994,000	6	http://en.chabio.com/
Changchun SinoBiomaterials Co	Changchun, China	Preclinical	Private	Biomaterials	$3,647,775	131	http://sinobiom.globalchemmade.com/
Citospin	Valladolid, Spain	Commercial	Private	Cells and Biomaterials	$1,519,787	16	https://www.citospin.com/
Co.don	Germany	Commercial	Private	Cells and Biomaterials	$11,645,100	150	https://www.codon.de/
Cognate BioServices Inc	Baltimore, MD	Commercial	Private	Stem Cells	$12,548,567	30	https://www.cognatebioservices.com/
CollaMedix Inc	Cleveland, OH	Commercial	Private	Cells and Biomaterials	$282,130	4	https://collamedixinc.com/
CONMED Corporation	Utica, NY	Commercial	Public	Cells and Biomaterials	$1,045,472,000	4,100	https://www.conmed.com/
Contura	London, England	Commercial	Private	Cells and Biomaterials	$11,515,443	33	https://contura.com/
Convelo Therapeutics	Cleveland, OH	Preclinical	Private	Stem Cells	$508,869	3	https://www.convelotx.com/
Cook Biotech	West Lafayette, IN	Commercial	Private	Biomaterials	$33,823,989	120	https://www.cookbiotech.com/
Cook MyoSite	Pittsburgh, PA	Commercial	Private	Stem Cells	$22,945,023	160	https://www.cookmyosite.com/
CorestemChemon Inc.	Gyeonggi, South Korea	Clinical Trials	Private	Stem Cells	$34,627,164	394	https://www.corestemchemon.com/
CTM Medical	Palm Beach, FL	Commercial	Private	Cells and Biomaterials	$797,839	16	https://www.ctmbiomedical.com/
Curasan	Wake Forest, NC	Commercial	Private	Biomaterials	$373,520	1	https://curasaninc.com/
Curi Bio	Seattle, WA	Commercial	Private	Cells and Biomaterials	$3,028,329	23	https://www.curibio.com/
Cyfuse Biomedical KK	Tokyo, Japan	Commercial	Private	Cells and Biomaterials	$2,700,354	26	https://en.cyfusebio.com/
Cynata Therapeutics Limited	Victoria, Australia	Clinical Trials	Private	Stem Cells	$45,975	100	https://www.cynata.com/
CytoMed Therapeutics Pte	Johor, Malaysia	Clinical Trials	Private	Stem Cells	$182,612	4	https://w2.cytomed.sg/
Cytopeutics Sdn. Bhd.	Cyberjaya, Malaysia	Clinical Trials	Private	Stem Cells	$4,101,696	36	https://www.cytopeutics.com/
Cytori Therapeutics	Raffles Quay, Singapore	Commercial	Private	Stem Cells	$2,872,500	54	https://www.cytori.com/
Dentsply Sirona Implants and Consumables	Charlotte, NC	Commercial	Public	Biomaterials	$3,922,000,000	600	https://www.dentsplysirona.com/
Depuy (J&J)	New Brunswick, NJ	Commercial	Private	Biomaterials	$1,808,333,277	12,000	https://www.jnjmedtech.com
Deverra Therapeutics	Seattle, WA	Commercial	Private	Stem Cells	$1,108,930	7	https://www.deverratx.com/
Dimension Inx	Chicago, IL	Commercial	Private	Cells and Biomaterials	$2,443,404	14	https://www.dimensioninx.com/
Dome Therapeutics	Woodstock, MD	Preclinical	Private	Stem Cells			https://liew76.wixsite.com/mysite-1
Dynomics	San Francisco, CA	Preclinical	Private	Cells and Biomaterials	$182,612	4	https://www.dynomics.com/
ECM-Therapeutics	Warrendale, PA	Clinical Trials	Private	Cells and Biomaterials	$811,240	6	https://ecmtherapeutics.com/
Educell	Slovenia	Clinical Trials	Private	Stem Cells	$1,441,562	19	https://www.educell.si/
EHL Bio Co.	Seoul, South Korea	Clinical Trials	Private	Stem Cells	$11,913,396	34	https://www.ehlbio.co.kr/
Elevate Bio	Waltham, MA	Commercial	Private	Stem Cells	$30,151,394	204	https://elevate.bio/
Emanate Biomedical	New York, NY	Commercial	Private	Cells and Biomaterials	$63,798	5	https://www.emanatebiomedical.com/
Endomimetics	Birmingham, AL	Preclinical	Private	Cells and Biomaterials	$157,465	2	https://endomimetics.com/
EpiBone	Jersey City, NJ	Commercial	Private	Cells and Biomaterials	$2,755,189	30	https://www.epibone.com/
Epirium Bio	San Diego, CA	Clinical Trials	Private	Stem Cells	$1,011,261	1	https://epirium.com/
EpiSkin	France	Commercial	Private	Cells and Biomaterials	$14,171,129	58	https://www.episkin.com/
eQcell	Ontario, Canada	Commercial	Private	Stem Cells	$474,890	2	https://www.eqcell.com/
Escape Therapeutics Inc	San Jose, CA	Preclinical	Private	Stem Cells	$78,949	6	http://escapetherapeutics.com/
ExacTech	Gainesville, FL	Commercial	Public	Biomaterials	$313,397,000	1,000	https://www.exac.com/
ExCellThera	Montreal, Quebec	Clinical Trials	Private	Stem Cells	$546,432	6	https://excellthera.com/
Fate Therapeutics	San Diego, CA	Clinical Trials	Public	Stem Cells	$96,300,000	80	https://fatetherapeutics.com/
Fibr align Corporation	Union City, CA	Commercial	Private	Cells and Biomaterials	$628,046	2	https://www.fibralignbio.com/
FibroBiologics	Houston, TX	Clinical Trials	Private	Stem Cells	$226,538	6	https://fibrobiologics.com/
Fidia Farmaceutici	Italy	Commercial	Private	Biomaterials	$427,975,524	1,022	http://www.fidiapharma.it
Fluicell AB	Mölndal, Sweden	Preclinical	Private	Cells and Biomaterials	$284,164	20	https://www.fluicell.com/
FluidForm	Waltham, MA	Preclinical	Private	Cells and Biomaterials	$1,149,673	8	https://www.fluidformbio.com/
Fujifilm Cellular Dynamics	Madison, WI	Preclinical	Public	Stem Cells	$74,513,073	150	https://www.fujifilmcdi.com/
FuturaMedical	Surrey, United Kingdom	Commercial	Public	Biomaterials	$527,118	12	https://www.futuramedical.com/
Gamida Cell	Boston, MA	Commercial	Private	Stem Cells	$5,836,119	35	https://www.gamida-cell.com/
Gelesis	Boston, MA	Commercial	Public	Cells and Biomaterials	$25,767,000	103	https://www.gelesis.com/
Gelmetix	Cheshire, United Kingdom	Clinical Trials	Private	Cells and Biomaterials	$679,692	8	https://www.gelmetix.com/
GELOMICS PTY	Queensland, Australia	Commercial	Private	Cells and Biomaterials	$19,286	22	https://www.gelomics.com/
GenAssist	Greenwood Village, CO	Preclinical	Private	Biomaterials			https://genassist.co/
GeniPhys	Indianapolis, IN	Commercial	Private	Cells and Biomaterials	$68,631	1	https://www.geniphys.com/
GID Bio	Louisville, CO	Commercial	Private	Cells and Biomaterials	$69,382	5	https://gidbio.com/
Gli align	London, England	Preclinical	Private	Cells and Biomaterials	$60,060	2	https://glialign.com/
Greenstone Biosciences	Palo Alto, CA	Commercial	Private	Stem Cells	$693,660	10	https://greenstonebio.com/
Grigory Karmy	Ontario, Canada	Clinical Trials	Private	Stem Cells	$383,520	2	https://karmyclinic.com/
Guidon Pharmaceutics	Beijing, China	Commercial	Private	Stem Cells	$1,083,000	28	http://www.guidonpharmaceutics.com/
Gunze Limited	Kyoto, Japan	Commercial	Private	Cells and Biomaterials	$1,008,934,510	5,214	https://www.gunze.co.jp/
Gwo Xi Stem Cell Applied Technology Co.	Hsinchu County, Taiwan	Clinical Trials	Private	Stem Cells	$5,830,666	49	https://en.gwoxi.com.tw/
H-CYTE	Tampa, FL	Commercial	Public	Cells and Biomaterials	$453,460	8	https://hcyte.com/
HEALIOS K.K.	Tokyo, Japan	Clinical Trials	Private	Stem Cells	$648,990	71	https://www.healios.co.jp/
Heart Cells Company	Edenbridge, England	Clinical Trials	Private	Stem Cells	$454,314	9	https://www.heartcellsfoundation.com/
HeartBeat.bio	Vienna, Austria	Preclinical	Private	Stem Cells		7	https://heartbeat.bio/
Heartseed	Tokyo, Japan	Clinical Trials	Private	Stem Cells	$9,298,944	43	https://heartseed.jp/
Help Therapeutics	Jiangsu, China	Preclinical	Private	Stem Cells	$42,808	45	https://en.helptherapeutics.com/
Histocell	Derio, Spain	Clinical Trials	Private	Stem Cells	$2,484,758	32	https://histocell.com
Histogenics Corporation	Malvern, PA	Clinical Trials	Private	Cells and Biomaterials	$163,814	8	https://ocugen.com/
Hologenix	Pacific Palisades, CA	Clinical Trials	Private	Biomaterials	$521,929	5	https://hologenixllc.com/
Holostem Terapie Avanzate S.r.l.	Modena, Italy	Commercial	Private	Stem Cells	$1,532,524	81	https://www.holostem.com/
Honya Medical	Tainan, Taiwan	Commercial	Private	Stem Cells	$615,976	8	https://www.honya-m.com/
HUB Organoids	Utrecht, Netherlands	Commercial	Private	Stem Cells	$772,518	4	https://www.huborganoids.nl/
Humabiologics	Phoenix, Arizona	Commercial	Private	Cells and Biomaterials	$2,250,265	13	https://humabiologics.com/
Humacyte	Research Triangle, NC	Preclinical	Public	Biomaterials	$1,565,000	137	https://humacyte.com/
Hy2Care BV	Enschede, Netherlands	Clinical Trials	Private	Cells and Biomaterials	$26,331	8	https://www.hy2care.com/
Hybrid Organ GMBH	Germany	Clinical Trials	Private	Cells and Biomaterials	$892,636	10	https://www.hybrid-organ.com/
Hyperstem SA	Lugano, Switzerland	Preclinical	Private	Stem Cells	$1,269,272	10	https://hyperstems.wordpress.com/
Hyundai Bioland Co.	Chungcheongbuk-do, Korea	Preclinical	Private	Biomaterials	$83,662,920	320	https://www.hyundaibioland.co.kr/
IBSA Pharma Inc	France	Commercial	Private	Cells and Biomaterials	$711,354	5	https://www.ibsa-pharma.fr/
iCamuno Biotherapeutics	Jiangsu, China	Preclinical	Private	Stem Cells	$1,734,814	38	https://www.icamunobio.com/
iHeart Japan Corporation	Kyoto, Japan	Commercial	Private	Stem Cells	$987,946	13	http://www.iheartjapan.jp/
Ilaya Medical Company	Kiev, Ukraine	Preclinical	Private	Stem Cells			https://ae.ilaya.com/
IMEL	Waltham, MA	Preclinical	Private	Stem Cells	$102,217	3	https://imelbiotx.com/
Immusoft	Seattle, WA	Clinical Trials	Private	Stem Cells	$1,014,419	1	https://www.immusoft.com/
ImStem Biotechnology	Farmington, CT	Clinical Trials	Private	Stem Cells	$531,317	3	https://www.imstem.com/
INDUSTRIE BIOMEDICHE INSUBRI SA	Ticino, Switzerland	Commercial	Private	Biomaterials	$310,536	4	https://www.ibi-sa.com/
InGeneron	Houston, TX	Clinical Trials	Private	Stem Cells	$1,878,537	8	https://ingeneron.com/
Inion Ltd	Finland	Commercial	Private	Biomaterials	$5,730,227	16	https://www.inion.com/
Innervace	New York, NY	Preclinical	Private	Cells and Biomaterials	$41,517	1	https://www.innervace.com/
Innovacell	Innsbruck, Austria	Commercial	Private	Stem Cells	$278,240	14	https://innovacell.at/en/
Integra LifeSciences	Princeton, NJ	Commercial	Public	Biomaterials	$1,557,666,000	3,700	https://www.integralife.com/
International Stem Cell Corporation	Carlsbad, CA	Preclinical	Public	Stem Cells	$8,180,000	35	https://www.internationalstemcell.com/
InVivo Therapeutics	Burlington, MA	Clinical Trials	Private	Cells and Biomaterials	$4,281,758	7	https://www.invivotherapeutics.com/
Japan Tissue Engineering Co.	Aichi, Japan	Commercial	Public	Cells and Biomaterials	$15,074,667	215	https://www.jpte.co.jp/
jCyte	Newport Beach, CA	Clinical Trials	Private	Stem Cells	$883,172	2	https://www.jcyte.com/
Jiuzhitang Maker (Beijing) Cell Technology Co.	Beijing, China	Clinical Trials		Stem Cells			https://en.jztmaker.com/
Juventas Cell Therapy	Beijing, China	Clinical Trials	Private	Stem Cells	$11,586,120	230	http://www.juventas.cn/
Kang Stem Biotech Co.	Seoul, South Korea	Commercial	Private	Stem Cells	$12,193,148	688	https://kangstem.com/
Karis Bio	Seoul, South Korea	Preclinical	Private	Stem Cells	$182,612	9	https://karisbio.com/
KeraNetics	Winston-Salem, NC	Commercial	Private	Biomaterials	$4,321,838	28	https://www.keranetics.com/
Kerecis	Reykjavik, Iceland	Commercial	Private	Cells and Biomaterials	$15,433,220	58	https://www.kerecis.com/
KLISBio	Milan, Italy	Preclinical	Private	Biomaterials			https://www.klis.bio/
Kolon TissueGene	Rockville, MD	Clinical Trials	Private	Stem Cells	$4,826,189	20	https://www.tissuegene.com/
K-Pharma	Tokyo, Japan	Preclinical	Private	Stem Cells	$15,697,024	18	https://en.kpharma.co.jp/
Kuros Biosurgery	Switzerland	Clinical Trials	Private	Biomaterials	$310,536	4	https://kurosbio.com/
Lattice Medical	Loos, France	Clinical Trials	Private	Cells and Biomaterials	$31,158	10	https://www.lattice-medical.com/
Lavior Pharma	Miami, FL	Commercial	Private	Biomaterials	$2,588,820	13	https://lavior.com/
LifeNet Health	Virginia Beach, VA	Commercial	Private	Cells and Biomaterials	$455,372,311	500	https://www.lifenethealth.org/
LifeSprout	Baltimore, MD	Clinical Trials	Private	Biomaterials	$573,767	4	https://www.lifesproutbio.com/
Likarda	Kansas City, MO	Commercial	Private	Cells and Biomaterials	$508,667	4	https://likarda.com/
LinkoCare Life Sciences AB	Linköping, Sweden	Commercial	Private	Cells and Biomaterials		2	https://www.linkocare.com/
Longeveron	Miami, FL	Clinical Trials	Public	Stem Cells	$1,222,000	24	https://longeveron.com/
LyGenesis	Pittsburgh, PA	Clinical Trials	Private	Stem Cells			https://www.lygenesis.com/
MatTek Corporation	Ashland, MA	Commercial	Private	Cells and Biomaterials	$19,378,610	80	https://www.mattek.com/
Medeor Therapeutics	San Francisco, CA	Clinical Trials	Private	Stem Cells	$2,812,903	27	https://www.medeortx.com/
Medi	Whitsett, NC	Commercial	Private	Biomaterials	$32,626,188	130	https://www.mediusa.com/
Medicem Technology SRO	Prague, Czech Republic	Preclinical	Private	Biomaterials	$4,539,826	17	https://www.medicem.com/
Medipost Co	Gyeonggi, South Korea	Clinical Trials	Public	Stem Cells	$48,022,348	294	https://www.medi-post.co.kr/
Medtronic	Minneapolis, MN	Commercial	Public	Biomaterials	$3,981,465,304	57,711	https://www.medtronic.com/
Meluha Life Sciences SDN BHD	Putrajaya, Malaysia	Clinical Trials	Private	Stem Cells	$878,440	10	https://meluhatx.com/
Mepsgenlab	Seoul, South Korea	Preclinical	Private	Cells and Biomaterials	$133,144	18	https://www.mepsgen.com/
Meridigen Biotech Co.	Taipei City, Taiwan	Clinical Trials	Private	Stem Cells	$15,908,456	92	http://www.meridigen.com/
Mesoblast	Melbourne, Australia	Clinical Trials	Private	Stem Cells	$13,300,687	8	https://www.mesoblast.com/
MIACH Orthopedics	Westborough, MA	Commercial	Private	Cells and Biomaterials	$1,137,453	7	https://www.miachortho.com/
Mimedx	Marietta, GA	Commercial	Public	Cells and Biomaterials	$267,841,000	735	https://www.mimedx.com/
MIMETAS	Oegstgeest, Netherlands	Preclinical	Private	Cells and Biomaterials	$4,752,085	94	https://www.mimetas.com/
Mimetis Biomaterials	Barcelona, Spain	Commercial	Private	Biomaterials	$39,188	10	https://mimetis.com/
Minovia Therapeutics	Tirat Carmel, Israel	Preclinical	Private	Stem Cells	$519,806	28	https://minoviatx.com/
MIRAE CELL BIO	Seoul, South Korea	Clinical Trials		Stem Cells			http://miraecellbio.com/
Miromatrix Medical	Silver Spring, MD	Clinical Trials	Public	Cells and Biomaterials	$953,470	36	https://www.unither.com/
Morphocell Technologies	Laval, Canada	Preclinical	Private	Stem Cells	$3,600,784	11	https://www.morphocell.com/
Nadir s.r.l	Venice, Italy	Commercial	Private	Biomaterials	$30,074	3	https://nadir-tech.it/
Nanofiber Solutions	Dublin, Ohio	Preclinical	Private	Biomaterials	$1,049,827	12	https://nanofibersolutions.com/
NanoRegMed	London, England	Commercial	Private	Cells and Biomaterials	$63,417	2	https://www.nanoregmed.com/
NC Biomatrix BV	Eindhoven, Netherlands	Preclinical	Private	Biomaterials	$110,000	3	https://ncbiomatrix.com/
NeoBiosis	Gainesville, FL	Clinical Trials	Private	Stem Cells	$3,121,696	16	https://www.neobiosis.com/
Neotherix	United Kingdom	Clinical Trials	Private	Biomaterials	$157,364	4	https://www.neotherix.com/
Neuralstem	Rockville, MD	Clinical Trials	Private	Stem Cells	$110,000	4	https://www.neuralstem.com/
Neurona Therapeutics	South San Francisco, CA	Clinical Trials	Private	Stem Cells	$9,134,995	17	https://www.neuronatherapeutics.com/
Neurotech	Lincoln, RI	Clinical Trials	Private	Cells and Biomaterials	$3,691,533	15	http://www.neurotechusa.com/
NextCell Pharma Ab	Huddinge, Sweden	Clinical Trials	Private	Stem Cells	$544,525	20	https://www.nextcellpharma.com/
Northern Therapeutics	Quebec, Canada	Clinical Trials	Private	Stem Cells			https://www.northernther.com/
Novadip	Mont-Saint-Guibert, Belgium	Clinical Trials	Private	Cells and Biomaterials		36	https://novadip.com/
Noveome Biotherapeutics	Pittsburgh, PA	Clinical Trials	Private	Stem Cells	$5,273,561	35	https://noveome.com/
Novo Nordisk	Bagsværd, Denmark	Clinical Trials	Private	Stem Cells	$114,802,345	390	https://www.novonordisk.com/
NovoHeart	Boston, MA	Commercial	Private	Stem Cells	$72,291	5	https://www.novoheart.com/
NS Pharma	Paramus, NJ	Clinical Trials	Private	Stem Cells	$11,228,715	45	https://www.nspharma.com/
Nuo Therapeutics	Houston, TX	Commercial	Private	Cells and Biomaterials	$547,402	3	https://www.nuot.com/
Nuwacell Biotechnologies Co.	Hefei, China	Clinical Trials	Private	Stem Cells	$5,419,200	100	https://en.nuwacell.com/
Obatala Sciences	New Orleans, LA	Commercial	Private	Cells and Biomaterials	$457,925	2	https://www.obatalasciences.com/
Oligo Medic	Quebec, Canada	Commercial	Private	Cells and Biomaterials	$2,581,656	11	https://www.oligomedic.com/
Opexa Therapeutics	The Woodlands, TX	Clinical Trials	Public	Stem Cells	$97,000	2	https://www.opexatherapeutics.com/
Opsis Therapeutics	Madison, WI	Preclinical	Private	Stem Cells			https://opsistx.com/
Orbsen Therapeutics	Galway, Ireland	Clinical Trials	Private	Stem Cells	$310,536	9	https://orbsentherapeutics.com/
Orca Biosystems	Menlo Park, CA	Clinical Trials	Private	Stem Cells	$12,266,373	101	https://orcabio.com/
OrganaBio	South Miami, FL	Commercial	Private	Stem Cells	$2,433,887	15	https://www.organabio.com/
Organogenesis	Canton, MA	Commercial	Public	Cells and Biomaterials	$450,893,000	910	https://organogenesis.com/
Organovo	San Diego, CA	Clinical Trials	Public	Cells and Biomaterials	$370,000	24	https://organovo.com/
Osiris Therapeutics	London, England	Commercial	Public	Cells and Biomaterials	$142,824,000	360	https://www.smith-nephew.com/
Osteopore International	MedTech Park, Singapore	Commercial	Private	Cells and Biomaterials	$214,575	5	https://www.osteopore.com/
Pandorum International	Bangalore, India	Preclinical	Private	Cells and Biomaterials	$64,156	6	https://pandorum.com/
Paragen Technologies	Dublin, OH	Commercial	Private	Cells and Biomaterials	$77,860	6	https://www.paragentechnologies.com/
PharmaBio Corporation	Kanagawa, Japan	Clinical Trials	Private	Stem Cells	$1,270,004	28	https://www.pharmabio.co.jp/
PharmaExceed	Pavia, Italy	Commercial	Private	Stem Cells		4	https://www.pharmaexceed.com/
Pharmicell Co.	Seoul, South Korea	Clinical Trials	Private	Stem Cells	$45,016,136	1,395	http://www.pharmicell.com/
PhoenixSongs Biologicals	Branford, CT	Commercial	Private	Stem Cells	$477,843	4	http://www.phoenixsongsbio.com/
PolarityTE	Salt Lake City, UT	Clinical Trials	Public	Cells and Biomaterials	$814,000	80	https://www.polarityte.com/
Polymedics	Denkendorf, Germany	Commercial	Private	Cells and Biomaterials	$1,009,829	9	https://polymedics.com/
PolyNovo Biomaterials Pty	Victoria, Australia	Commercial	Private	Cells and Biomaterials	$17,208,733	250	https://polynovo.com/
PrimeGen US	Irvine, CA	Clinical Trials	Private	Stem Cells	$2,667,280	20	https://primegenus.com
ProKidney	Winston-Salem, NC	Clinical Trials	Private	Stem Cells	$3,518,161	20	https://prokidney.com/
Propagenix	Gaithersburg, MD	Commercial	Private	Stem Cells	$724,893	4	https://propagenix.com/
PT. Prodia Stem Cell Indonesia	Jakarta, Indonesia	Preclinical	Private	Stem Cells			https://prostem.co.id/
PuREC Co.	Tokyo, Japan	Clinical Trials	Private	Stem Cells	$817,549	12	https://www.purec-global.com/
Q Therapeutics	Salt Lake City, UT	Commercial	Private	Stem Cells	$1,731,598	14	https://www.qthera.com/
Quthero	Miami, FL	Preclinical	Private	Biomaterials	$73,490	3	https://quthero.com/
R3 Stem Cell	Phoenix, AZ	Commercial	Private	Stem Cells	$237,935	8	https://r3stemcell.com/
R3 Vascular	Mountain View, CA	Clinical Trials	Private	Cells and Biomaterials	$565,876	4	https://www.r3vascular.com/
ReGelTec	Baltimore, MD	Clinical Trials	Private	Cells and Biomaterials	$499,256	10	https://regeltec.com/
ReGen Theranostics	Rochester, MN	Preclinical	Private	Stem Cells	$293,669	3	https://regentheranostics.com/
REGENERA SA	Lugano, Switzerland	Preclinical	Private	Cells and Biomaterials	$310,536	4	https://regenera.at/
Regeneration Biomedical	Newport Beach, CA	Clinical Trials	Private	Stem Cells	$920,266	11	https://www.regenerationbiomedical.com/
Regenerative Patch Technologies	San Francisco, CA	Clinical Trials	Private	Cells and Biomaterials	$244,857	8	https://regenerativepatch.com/
Regeneris Medical	North Attleboro, MA	Commercial	Private	Stem Cells	$736,404	6	https://www.regenerismedical.com/
Regeneus	Paddington, Australia	Clinical Trials	Private	Stem Cells	$1,917,426	42	https://regeneus.com.au/
Regenics A/S	Norway	Preclinical	Private	Biomaterials	$271,989	3	https://www.regenics.no/
Regenosca SA	Lausanne, Switzerland	Clinical Trials	Private	Biomaterials	$388,170	5	https://www.regenosca.com/
Regulaxis	Romainville, Italy	Preclinical	Private	Stem Cells	$34,345	3	http://www.regulaxis.com/
Rejoni	Bedford, MA	Clinical Trials	Private	Cells and Biomaterials	$392,150	2	https://rejoni.com/
RenovoDerm	Dublin, OH	Commercial	Private	Cells and Biomaterials	$134,364	5	https://www.renovoderm.tech/
Replication Medical	Monmouth Junction, NJ	Commercial	Private	Cells and Biomaterials	$270,815	4	http://www.replicationmedical.com/
ReproCELL	Yokohama, Japan	Commercial	Private	Stem Cells	$5,938,185	20	https://www.reprocell.com/
REVA Medical	San Diego, CA	Commercial	Public	Cells and Biomaterials	$7,876,802	51	https://www.revamedical.com/
Revivicor	Blacksburg, VA	Clinical Trials	Private	Cells and Biomaterials	$2,756,835	25	https://www.revivicor.com/
RHEACELL & Co.	Heidelberg, Germany	Clinical Trials	Private	Stem Cells	$1,552,680	20	https://www.rheacell.com/
Ronawk	Overland Park, KS	Commercial	Private	Cells and Biomaterials	$678,537	10	https://ronawk.com/
RoosterBio	Frederick, MD	Commercial	Private	Stem Cells	$2,557,396	7	https://www.roosterbio.com/
Rousselot B.V. Gent	Ghent, Belgium	Commercial	Private	Cells and Biomaterials	$711,656	4	https://www.rousselot.com/
RTI Surgical	Gainesville, FL	Commercial	Private	Biomaterials	$33,367,586	200	https://www.rtix.com/
Sana Biotechnology	Seattle, WA	Preclinical	Private	Stem Cells	$4,632,719	18	https://sana.com/
SanBio Company Limited	Tokyo, Japan	Clinical Trials	Private	Stem Cells	$46,738,688	65	https://www.sanbio.com/
Satellite Biosciences	Watertown, MA	Preclinical	Private	Cells and Biomaterials	$1,072,266	4	https://satellite.bio/
Sclnow Biotechnology Co.	Beijing, China	Commercial	Private	Stem Cells	$34,108,740	180	http://en.sclnow.com/
SeaSpine	Carlsbad, CA	Commercial	Private	Biomaterials	$28,046,502	100	https://www.seaspine.com/
Secant Group	Telford, PA	Commercial	Private	Cells and Biomaterials	$64,205,040	150	https://secant.com/
Sentien Biotechnologies	Lexington, MA	Clinical Trials	Private	Stem Cells	$804,122	4	https://sentienbiotech.com/
SEWON Cellontech	Korea	Commercial	Private	Biomaterials	$10,586,444	100	http://www.cellontech.com
Shanghai Celliver Biotechnology Co.	Shanghai, China	Commercial		Cells and Biomaterials			http://www.celliverbio.com/
Shiningbiotek Company Limited	Taipei City, Taiwan	Preclinical	Private	Stem Cells	$3,652,000	200	https://www.shining-biotech.com/
Shoreline Biosciences	San Diego, CA	Preclinical	Private	Stem Cells	$2,074,662	25	https://shorelinebio.com/
SILTISS	Saint-Viance, France	Preclinical	Private	Cells and Biomaterials	$33,954	4	https://www.siltiss.fr
Skin2NeuronPty	Surry Hills, Australia	Preclinical	Private	Stem Cells	$456,303	11	https://www.skin2neuron.org/
SkinAxis	Cedar Knolls, NJ	Commercial	Private	Cells and Biomaterials	$266,835	6	https://www.skinaxis.com/
Skye Biologics	El Segundo, CA	Commercial	Private	Cells and Biomaterials	$1,016,527	40	https://www.skyebiologics.com/
Smith & Nephew	Memphis, Tennessee	Commercial	Private	Biomaterials	$694,350,396	1,849	https://www.smith-nephew.com/
Soft Tissue Regeneration/Biorez	Utica, NY	Commercial	Public	Biomaterials	$1,045,472,000	4,100	https://www.conmed.com/
SolasCure Limited	Cambridge, England	Clinical Trials	Private	Cells and Biomaterials	$3,826,444	11	https://solascure.com/
Stemedica Cell Technologies	San Diego, CA	Clinical Trials	Private	Stem Cells	$9,794,582	48	https://www.stemedica.com/
Stempeutics	Bangalore, India	Commercial	Private	Stem Cells	$394,330	28	https://www.stempeutics.com/
StimLabs	Roswell, GA	Commercial	Private	Cells and Biomaterials	$2,664,738	15	https://stimlabs.com/
Sumitomo Dainippon Pharma	Osaka, Japan	Clinical Trials	Private	Stem Cells	$2,363,174	24	https://www.sumitomo-pharma.com/
SweetBio	Memphis, TN	Commercial	Private	Cells and Biomaterials	$9,821,973	10	https://www.sweetbio.com/
Swiss Medica XXI Century	St. Gallen, Switzerland	Preclinical	Private	Stem Cells			https://www.startstemcells.com/
SymbiOx	Macul, Chile	Clinical Trials	Private	Cells and Biomaterials			https://www.symbiox.org/
Taiwan Bio Therapeutics Co.	Tapei City, Taiwan	Preclinical	Private	Stem Cells	$1,444,055	20	https://twbio-thera.com/
Taiwan Mitochondrion Applied Technology Co	Zhubei, Taiwan	Clinical Trials	Private	Stem Cells	$913,060	20	https://en.mitobiomed.com/
Tarian Medical	Dublin, OH	Preclinical	Private	Biomaterials	$71,608	5	https://www.paragentechnologies.com/tarian-medical
Tenpoint Therapeutics Limited	London, England	Clinical Trials	Private	Stem Cells	$647,497	68	https://www.tenpointtherapeutics.com/
Tepha	Cambridge, MA	Preclinical	Private	Biomaterials	$11,350,946	63	http://www.tepha.com
Tetec Tissue Engineering Technologies AG	Reutlingen, Germany	Commercial	Private	Cells and Biomaterials	$13,100,540	13	https://www.tetec-ag.de/en.html
The Electrospinning Company	Oxfordshire, United Kingdom	Commercial	Private	Cells and Biomaterials	$1,447,269	23	https://www.electrospinning.co.uk/
Thomas Advanced Medical	Los Angeles, CA	Preclinical	Private	Stem Cells	$210,580	5	https://thomasadvancedmedical.com/
Throne Biotechnologies	Paramus, NJ	Clinical Trials	Private	Stem Cells	$187,065	10	https://thronebio.com/
Thymmune Therapeutics	Cambridge, MA	Preclinical	Private	Stem Cells	$41,517	1	https://www.thymmune.com/
Tianjin Weikai Bioengineering	Tianjin, China	Clinical Trials	Private	Cells and Biomaterials	$5,803,000	30	http://www.tj.xinhuanet.com/web/uninova/en/index.htm
TiGenix SAU	Madrid, Spain	Clinical Trials	Private	Stem Cells	$54,138,711	4	https://www.asebio.com/en/members/directory/tigenix
TISSIUM	Paris, France	Clinical Trials	Private	Cells and Biomaterials	$7,920,498	76	https://tissium.com/
Tissue Click	Hove, United Kingdom	Commercial	Private	Cells and Biomaterials	$501,170	4	https://www.tissueclick.com/
Tissue Regenix	United Kingdom	Commercial	Private	Biomaterials	$24,476,000	85	https://www.tissueregenixus.com
TissueByNet Corp	Tokyo, Japan	Commercial		Cells and Biomaterials			https://en.tissuebynet.com/
TissueTech	Miami, FL	Commercial	Private	Cells and Biomaterials	$18,738,094	150	https://biotissue.com/
Titan Pharma	San Francisco, CA	Clinical Trials	Public	Biomaterials	$557,000	11	http://www.titanpharm.com
TransTissue Technologies	Berlin, Germany	Commercial	Private	Cells and Biomaterials	$1,086,876	14	https://transtissue.com/
Tristem Limited	United Kingdom	Clinical Trials	Private	Stem Cells	$76,459	4	http://www.tristemcorp.com
Trustem	Lake Forest, IL	Commercial	Private	Stem Cells	$342,221	5	https://trustemcell.com/
Tuohua Biological Technology Co.	Jilin, China	Commercial	Private	Stem Cells	$5,425,400	62	http://www.tuohuashengwu.com/
Typeone Srl	Lecce, Italy	Preclinical	Private	Cells and Biomaterials	$359,121	19	https://www.typeone.it/
U.S. Stem Cell Inc	Sunrise, FL	Clinical Trials	Public	Stem Cells	$82,049	2	https://us-stemcell.com/
UnicoCell Biomed CO.	Taipei City, Taiwan	Clinical Trials	Private	Stem Cells	$464,634	30	https://www.unicocell.com/
Ventrix	San Diego, CA	Clinical Trials	Private	Cells and Biomaterials	$486,226	1	https://ventrixbio.com/
Vericel Corporation	Cambridge, MA	Commercial	Public	Cells and Biomaterials	$164,365,000	273	https://www.vcel.com/
Vetherapy	San Francisco, CA	Commercial	Private	Stem Cells	$297,770	5	https://www.vetherapy.co/
VetStem	Poway, CA	Commercial	Private	Stem Cells	$988,605	11	http://www.vet-stem.com
Videregen Limited	Leeds, United Kingdom	Clinical Trials	Private	Cells and Biomaterials	$363,759	13	https://www.videregen.com/
Viscus Biologics	Cleveland, OH	Commercial	Private	Cells and Biomaterials	$3,466,663	15	https://viscusbiologics.com/
Vitro Biopharma	Golden, CO	Preclinical	Public	Stem Cells	$3,293,293	10	https://www.vitrobiopharma.com/
Vycellix	Tampa, FL	Preclinical	Private	Stem Cells	$98,366	8	https://vycellix.com/
Wright Medical Group	Memphis, TN	Commercial	Public	Biomaterials	$356,923,899	898	https://www.wright.com/
Xeltis	Eindhoven, Netherlands	Clinical Trials	Private	Cells and Biomaterials	$1,009,242	13	https://xeltis.com/
XenoTherapeutics	Boston, MA	Clinical Trials	Private	Cells and Biomaterials	$990,086	1	https://www.xenotx.org/
Xintela AB	Lund, Sweden	Clinical Trials	Private	Stem Cells		10	https://www.xintela.se/
Xtant Medical	Belgrade, MT	Commercial	Private	Biomaterials	$349,228	3	https://xtantmedical.com/
Zimmer Biomet	Warsaw, IN	Commercial	Public	Biomaterials	$6,939,900,000	1,842	https://www.zimmerbiomet.com/

FIG. 3.

(A) Heatmap of tissue engineering companies included in our review. Each point represents a single company, while the intensity is determined by their reported sales in USD. (B) Trend in number of tissue engineering companies identified over the last 3 decades of reviews. (C) Estimated sales volume from the tissue engineering industry. (D) Breakdown of identified tissue engineering company stages, product sectors, and attributed sales estimates.

The largest volume of companies, employees, and sales resides most heavily in the northeastern United States, continuing with historical trends (Fig. 3a). Nevertheless, there is a great deal of activity internationally as the industry has expanded to form large hubs worldwide. Of these, additional hotspots exist on the United States’ west coast, in the Asian Pacific (particularly in Japan and the Republic of Korea), and in Western Europe (specifically the United Kingdom, Germany, and Italy).

These 347 international companies made an estimated 53.7 billion USD in cumulative sales, 15 times the amount from a decade prior (Fig. 3c). The majority (77%) of all sales come from commercial-stage companies (41.4 bn USD), which represent about 47% of all companies (Fig. 3d). The extraordinary sales of commercial-stage tissue engineering companies are trailed by preclinical stage companies which have net about 11.6 bn USD, constituting 20% of all sales and representing 20% of all companies. Finally, about a third of companies are in the clinical trials phase and yield a small subset of the estimated cumulative sales totaling less than 1 bn USD.

The distribution of companies by product sector varies based on stage. Commercial companies are dominated by the ‘Cells and Biomaterials’ product sector, followed by ‘Stem Cell’ products and then ‘Biomaterials’ (Fig. 3d). In contrast, both preclinical and clinical trials are primarily dominated by companies pursuing stem cell products as their primary offering. We interpret this distribution to suggest that precommercial investigations are primarily interested in the capabilities and efficacies of cellular therapies, which are newer from a historical perspective. In this line of thinking, commercialized companies leverage well-studied and established biomaterials alongside novel understanding of cell behavior to produce their products.

Overall, the commercialization of tissue engineering technologies has continued its healthy expansion.

Ongoing Clinical Trials

The advancement of tissue engineered therapies to commercial translation unsurprisingly relies on the performance of safety and efficacy assessed through clinical trials. In this study, we focus briefly on the U.S. clinical trial landscape to provide one perspective of the advancement of the field. This subpopulation is of interest due to the heightened overall activity of tissue engineering within the United States and the abundant information that is readily available and openly shared.

We searched the ClinicalTrials.gov database for tissue engineering trial entries between 2019 and 2023, representing the previous five years since the last review. There were 3,388 clinical trial entries that satisfied our search criteria. Most studies were in trial phase 1 or 2 or combination trials performing investigations qualifying as both phase 1 and 2 (Fig. 4). These also represented the largest rates of clinical trial failure (e.g., withdrawal, termination, or suspension), as was evidenced by the decreased rate of failure for trials in phase 3. Most trials were interventional, to develop tissue engineered or regenerative medicine therapeutics.

FIG. 4.

Ongoing tissue engineering clinical trials from 2019 to 2023. Clinical trials are stratified by trial phase and status, with a representation of what subset of trials are interventional or observational.

Relative to the preclinical and commercial product sectors, companies in clinical trials make up a small fraction of sales which is to be expected. Interestingly, most of the companies we identified that were in clinical trials were investigating stem cell therapies (68%), followed by therapies involving both cells and biomaterials (27%) and those utilizing only biomaterials (5%) (Fig. 3d). The product sector distribution for clinical trial stage companies in juxtaposition with commercial companies is an interesting one, particularly because clinical trials stage companies immediately precede commercial ones. Nonetheless, the fraction of commercial companies is greatest for cell and biomaterial products. These differences may be clinically driven due to the likelihood of improvement for clinical efficacy when combining cell and biomaterials into a therapeutic or alternatively it may be a conscious business decision and an indication that multimodality approaches incur lower risk due to greater ease in defense of intellectual property. Nonetheless, the volume of companies involved in tissue engineering clinical trials is substantial and harbors great promise for the identification of therapeutic strategies to a host of diseases.

Preclinical Directions

Preclinical-stage companies are responsible for 20% of estimated cumulative sales and make up 20% of identified companies. These companies are operating in the stem cell, biomaterial, and cells and biomaterials product sectors to engineer biological products that can aid in the repair or replacement of lost function.

Stem cells

Approximately 51% of the companies operating in the preclinical space focus on the translation of stem cell therapies to the clinic. Half of these identified companies are in the United States, whereas international presence is concentrated in Canada, Europe, and Asia (Fig. 3a). Many of these companies are focused on the translation of allogeneic multipotent or pluripotent therapies to the clinic. These therapies have the advantage of harnessing the multilineage potential of these cells for a wide range of tissue applications, can be delivered to many patients for therapeutic efficacy, and require reduced manufacturing cost and improved scalability due to the use of a single or few donors. ³⁷ Companies like Vitro Biopharma, Shoreline Bio, Sana Biotechnology, Cellatoz Therapeutics, and Morphocell are working in this area to deliver rapidly translatable stem cell-derived therapies for various disease targets. In addition, companies are using innovative gene editing technology to overcome the barrier in immunological response caused using allogeneic cells. For example, Universal Cells, a subsidiary of Astellas Pharma Inc., is developing allogeneic pluripotent cells using gene editing to knock out the HLA receptor for the development of universal cells that can be administered to almost any patient. ³⁸

In the academic space, researchers are making strides to engineer more efficacious stem cell therapies that overcome the barriers currently experienced with stem cell delivery, such as isolation and expansion of cells for manufacturing, uncontrolled differentiation, and immune rejection. ³⁹ One solution that can make this therapy safer and more widely accepted is the use of an engineered kill switch that deactivates cells when they become defective. Martin et al. engineered genetically modified cells for iPSC-based therapies that can target the killing of injected human pluripotent stem cells that are undifferentiated or malfunctioning. ⁴⁰ This step will bring the cell therapy field one step closer to engineering cell products that are safe, efficacious, and able to restore tissue function.

Biomaterials

Companies in the preclinical sector that are focused on engineering biomaterial technologies make up 4% of total identified tissue engineering companies, a number that has decreased in previous years. Many of these companies are focused on the use of naturally derived biomaterials for scaffold or hydrogel fabrication to treat a wide range of diseases. 3D scaffolds can provide bioactive support for tissue formation, porosity for cell infiltration and migration, and mechanical properties mimicking the tissue of interest. ⁴¹ Natural biomaterials have the advantage of biocompatibility, enhanced bioactivity, and promotion of cell proliferation and migration. ⁴² Companies like Angiograft, Medicem, Klis Bio, and Quthero are developing a broad range of therapeutic naturally derived materials to treat diseases.

Academic researchers in the biomaterials space are similarly focused on utilizing scaffold and hydrogel technologies to regenerate tissue function, with an emerging interest in the use of decellularized materials. Decellularized tissues from allogeneic or xenogeneic sources are another attractive scaffold used for the regeneration of tissue due to their retention of proteins native to human tissue that provide the structural integrity needed to build tissues, such as collagen, laminin, fibronectin, and elastin. ⁴³ The decellularization process allows for removing immunogenic DNA content while preserving the extracellular matrix from native tissue, building a framework for cell integration and tissue vascularization. Qiu et al. fabricated decellularized periosteal hydrogels that showed the induction of macrophage function, promoted mesenchymal stromal cell differentiation, and stimulated more robust bone formation compared with collagen I hydrogels. ⁴⁴ The future expansion of decellularized tissue used for organ reconstruction to improve their bioactivity and minimize the body’s immune response can be explored by allowing for control over the degradation speed of the scaffolds, standardizing the quality control process for manufacturing of these materials, and incorporating vascular structures to encourage long-term survival and integration of the tissue. ⁴⁵

Cells and biomaterials

Companies in the preclinical space that are focused on products combining cells and biomaterials represent 5% of the identified tissue engineering companies. Most of these companies are headquartered in the United States, with few companies operating in parts of Europe and Asia. These companies are using tissue engineering technologies to combine cells with biomaterials to restore or regenerate tissue function. There are three primary technologies that companies are using in these areas as follows: (1) 3D bioprinting, (2) organoid technology, or (3) injectable hydrogel or scaffolding technologies. 3D bioprinting has emerged as an attractive additive manufacturing technique to assemble complex tissues through the precise deposition of cells and extracellular matrix. Companies like FluidForm Bio and BIOLIFE4D are using bioprinting to work toward the regeneration of whole organs to address the organ shortage. Organoid technologies are being developed for the in vitro design of multicellular self-organizing tissue models that can replicate tissue function, serving as an intermediate between preclinical and clinical models. Dynomics is using organoid technology to assemble in vitro models of cardiac tissue. Injectable hydrogels and implantable scaffolds provide a functional and supportive matrix for the delivery of therapeutic cells. Companies like Satellite Bio, Innervace, and Regenera lead the industry in the development of cell and material matrices that can regenerate lost tissue.

From an academic research perspective, many bioengineers are focused on the translation of tissue models using tissue engineering techniques like bioprinting, organoid fabrication, and organ-on-a-chip models. 3D printing strategies can build layer-by-layer structures composed of biocompatible materials in complex, anatomically relevant geometries. Extrusion-based, inkjet, stereolithography-based printing, and laser-assisted bioprinting are commonly used to engineer tissue constructs with feature resolutions ranging from 10 to 200 microns. ⁴⁶ The fabrication of multilayered tissues has been demonstrated to recapitulate the native 3D microenvironment for many tissue types. Recent advances involve the fabrication of complex tissues such as personalized 3D-printed nipple areolar complex grafts that can serve as long-term implants in mastectomy patients, showing great potential to transform the field of breast reconstruction. ⁴⁷ Research focusing on improving the complexity of these grafts through vascularization, stimuli-responsive shape, or function change and enhancing bioink formulation is ongoing to further capture the intricacy of biological tissues.

The use of multiple cell types and materials to fabricate 3D organoids furthers the complexity and function of the tissue model. Revah et al. demonstrated the generation of self-organizing iPSC-derived human cortical organoids that can successfully integrate and function in transplanted animal models. ⁴⁸ Similarly, organ-on-a-chip models are becoming more advanced to mimic the function of tissues and provide another source to study the drug response of tissues in vitro. In December 2022, the FDA announced that animal testing is no longer needed to translate drugs or biologics to clinical trials, accelerating the ability of cell-based assays, organoids, organ-on-a-chip, and artificial intelligence to rapidly and accurately screen drug products to facilitate the translation of more in vitro models to the clinic while maintaining the same safety, efficacy, and quality standards. ^49,50

Great strides have been made to move forward with the clinical translation of tissue-engineered products without animal testing. The field of tissue engineering is rapidly moving toward a future that involves the development of viable and translatable tissues to address the global organ shortage. For successful clinical translation of these therapeutics, researchers within the field of tissue engineering need to collaborate with physicians, regulatory agencies, and funding agencies to ensure that tissue engineered constructs meet the needs of patients, regulatory bodies, and potential investors.

Conclusions

Over the last 30 years, the tissue engineering and regenerative medicine field has made remarkable strides to expand into a multidisciplinary field. Originating as a promising concept, many advancements have been made following the discovery and implementation of technologies, including additive manufacturing modalities such as 3D bioprinting, reprogrammable iPSCs for therapeutic and diagnostic applications, and self-assembling organoids for in vitro tissue models. While the field has expanded globally, most companies with tissue-engineered products are heavily present in the United States, primarily in the Northeastern and Pacific regions. Internationally, companies are in the Asian Pacific countries of Japan, the Republic of Korea, and the Western European countries of the United Kingdom, Germany, and Italy and minimal presence in South America with one company coming out of Chile. The ‘Stem Cells’ and ‘Cells and Biomaterials’ sectors have shown the largest increase in companies compared to previous data collected, with ‘Stem Cells’ representing 68% of products in clinical trials and ‘Cells and Biomaterials’ representing 54% of products in the commercial stage. ³² Over the last five years, the tissue engineering market has grown by 40 billion USD. Part of this increase is attributable to efforts by the FDA to streamline the regulatory process by reorganizing and using alternative testing methods to address products with low yield or chemistry, manufacturing, and controls challenges when they arise.

To perform our assessment, we made great efforts to cast a wide net when identifying companies internationally, and to do so we replicated methods from several prior publications on commercialization of tissue engineering as a whole. ^{31 –34} However, these methods are not without their limitations. We identified companies from associations with results of database searches for literature and clinical trials using key terms related to tissue engineering. While we succeeded in identifying several thousand entries which we parsed for tissue engineering companies, the choice of databases and search terms may introduce some bias to the results. Second, many of our quantitative findings are reliant on the accuracy of international business databases, which while we believe these to be reliable, ⁵¹ may have some inaccuracies intractable by the authors. For example, in pinpointing estimates of cumulative sales and number of employees attributable to tissue engineering endeavors, we anticipate that our reports are more accurate for smaller organizations than for larger ones with multiple subsidiaries that may or may not also be performing tissue engineering. We attempted to account for this by only including the tissue engineering subsidiaries of large companies performing business in multiple sectors, when possible.

In the future, the dominance of stem cell-based products seen in companies within the clinical trial sector is expected to lead to more commercialization of these products depending upon success in clinical trial results and regulatory approval. The efforts in past 30 years of tissue engineering are being realized through the domination of ‘Cell and Biomaterial’ based products in the commercial sector, highlighting the growth of tissue engineering as a reputable field. While biomaterial products still represent a substantial portion of commercial and preclinical products, the functionalization of these materials with bioactive cellular products is now more dominant in the field—a shift only realized in the last five years.

Despite government and industry investment in the field, there are only a modest number of commercially available tissue engineered products classifiable by the native definitions of the field. The field has therefore embraced parallel or complementary technologies that address the goals of tissue engineering as the science and regulatory frameworks advance toward realization. Some might consider this as a failing of the field. However, considering the audacity of the approach—building implantable tissues—we suggest that the rate of clinical impact of the field is at worst appropriate and perhaps remarkable.

To appropriately triage new therapies, regulatory agencies have pursued adaptations that make clearer how innovative engineered tissues will be scrutinized as potential therapeutics and what role they will play in the assessment of therapies. In the United States, the FDA has responded to the complexity of these products and the significant amount of detail required to review them by establishing the Office of Therapeutic Products in 2022 and making modifications to the regulatory pipeline. ^49,52 While significant strides have been made in the last five years, there are still many remaining challenges for tissue engineered products. Production scale-up, product consistency, and reproducibility are all active challenges in the field. The most significant challenge is supplying adequate nutrition and oxygen, which, if solved, will result in achieving the original aspirations of the field: to develop fully functional tissue and organ constructs. In conclusion, over the last 30 years, the tissue engineering and regenerative medicine field has metamorphosized from a visionary concept to a tangible force, driving innovation in both the health care and biotechnology spaces. The field holds the potential to reshape the medical landscape, offering renewed hope for patients, researchers, and clinicians alike.

Authors’ Contributions

R.B.F., A.S., and P.H. contributed to the experimental design, data collection and analysis, and writing of the article. S.H., M.W., M.U., L.A.G., L.N., and M.Z.L. contributed to the data collection by assisting with company identification, inclusion/exclusion determination, and financial data acquisition. P.H. assisted with the article preparation. J.P.F. oversaw experiments, performed data analysis, and oversaw the article preparation.

Data Access Statement

Data from our experiments and analysis will be available upon reasonable request to the corresponding author.

Disclosure Statement

The authors declare no conflict of interest.

Funding Information

This project was supported by the National Institutes of Health (R01 HD112031, R01 CA279815, P41 EB023833), the Osteo Science Foundation (23052316), the Maryland Stem Cell Research Fund (MSCRFD-6126), and the MPower Professorship.