The Issue

Tissue engineering allows healthcare providers to regenerate tissue lost due to congenital conditions, disease, trauma, inflammation, cancer, aging, or surgery. Today, “simpler” tissues such as skin, cartilage, fat, and bone are mimicked by tissue engineering with increasing similarity in biomechanics, properties and behavior to native tissue, bringing these therapies closer to clinical reality for patients.

These advancements have the potential to transform care for patients with conditions such as (but not limited to) microtia, osteoarthritis, craniofacial trauma, cancer survivors (including breast cancer, skin cancer, bone cancer and lung cancer), cleft lip, bone defects, burn victims, wounded war veterans and patients affected by other medical or aesthetic complications.

For many of the indications mentioned, autografts (own tissue harvested at a different site), allografts (donor tissue) or synthetic implants are the only option to rebuild lost tissue. However, all carry significant limitations, including donor-site morbidity and lack of true anatomical restoration and thus incomplete recovery of function [1, 2]. In addition, allografts may risk disease transmission, and in certain cases resorption [3] and implants risk inflammation, extrusion and degradation. 

While tissue engineering is showing real promise to improve patient quality of life, translation from pre-clinical experiments to the clinic, and therefore the patient, is hampered by ambiguity in regulatory pathways [4, 5]: Tissue engineered products under the current FDA regulations may be considered medical devices, biologics or drugs, each requiring different regulatory requirements, further determined by the specifics of the tissue engineered construct.

In certain cases, the regulatory ambiguity delays the progression of highly effective, life quality-improving tissue engineered treatments, because costs and regulatory approval are unpredictable, in favour of less potent therapies, that follow a more predictable regulatory pathway. In the case of osteoarthritis, for example, clinical translation focuses on injectables, even if tissue-engineered constructs show more favourable improvements in pathology, because developing injectables is less costly, and follows an easier, more predictable regulatory pathway [6].

The regulatory ambiguity creates unpredictability in development timelines, evidentiary requirements, and overall regulatory expectations, in addition to already high upfront costs to engineer tissues.

Therefore, the absence of a clear regulatory framework further contributes to the high cost and risks of clinical translation. Tissue-engineered products often require complex, multi-phase clinical trials, specialized manufacturing, and long-term follow-up. Without a clear and predictable pathway, these trials become significantly more expensive and difficult to design, fund, and execute, especially for biomedical start-ups or academic institutes with less funding, creating a real barrier for the advancement of human medicine.

For patients, their discomfort is a daily reality. Chronic pain, loss of function, and changes in physical appearance, particularly in visible areas such as the face, can have profound effects on mental health, identity, and overall quality of life. In many cases, patients continue to undergo multiple invasive procedures because more advanced solutions have not yet reached the clinic.

Our Proposal

-We propose the development of a dedicated, transparent regulatory framework for tissue-engineered products, maintaining rigorous safety standards while enabling responsible innovation:

-Risk-based classification: Regulatory requirements should be proportionate to tissue complexity (e.g. number of different cell types within one tissue, cell turnover, systemic effects, stability), cell source, cell type, amount of expansion during culturing, and biological behavior.

-A separate regulatory framework for tissue engineered products, distinguishing cell-free and cell-based bioprinted scaffolds, expanded tissues and dECM scaffolds.

-Integration of existing scientific evidence: Prior clinical data, validated platforms, and emerging tools (e.g. organoids, epigenetics, transcriptomics, DNA sequencing and proteomics) should be leveraged to reduce unnecessary duplication, and improve predictability of tissue engineered constructs.

-Standardization and predictability: Clear guidance for products developed under established conditions, such as Good Manufacturing Practice (GMP), automated incubators and robotics would reduce uncertainty, increase predictability, lower development costs, and improve trial feasibility.

-Recognition of validated components: Previously characterized cell types, scaffolds, and manufacturing processes with established safety profiles should not require full re-evaluation in every application.

-Pathways for earlier patient access: With appropriate oversight and informed consent, patients with significant unmet medical need should have the opportunity to access promising therapies earlier in development.

Why This Matters

A clear and adaptive regulatory approach would:

-Accelerate the safe translation of regenerative medicine into clinical care

-Reduce unnecessary cost and complexity in clinical development

-Enable more therapies to successfully enter and complete clinical trials

-Encourage investment and innovation across academia and industry

-Most importantly, improve outcomes and quality of life for patients

The Hopewell Foundation for Regenerative Medicine is a patient-driven organization focused on advancing solutions that restore both function and identity, particularly in nasal and craniofacial reconstruction.

We believe innovation in medicine should not happen in isolation. It should happen with patients at the center. We urge continued collaboration between regulators, researchers, clinicians, and patient communities to ensure these therapies are developed safely and reach those who need them without unnecessary delay.

Sources

[1] Alqarni, M. A., Alhomayani, K. M., & Bukhary, H. A. (2026). Allograft use in foot and ankle reconstruction: indications, outcomes, and limitations. Journal of Musculoskeletal Surgery and Research, 10(1), 33–39.
https://journalmsr.com/allograft-use-in-foot-and-ankle-reconstruction-a-narrative-review-of-indications-outcomes-and-limitations/

[2] Zimmermann, G., & Moghaddam, A. (2011). Allograft bone matrix versus synthetic bone graft substitutes. Injury, 42, S16–S21.
https://www.sciencedirect.com/science/article/abs/pii/S0020138311003020

[3] Kridel, R. W., Ashoori, F., Liu, E. S., & Hart, C. G. (2009). Long-term use of irradiated homologous costal cartilage grafts in nasal reconstruction. Archives of Facial Plastic Surgery, 11(6), 378–394.
https://jamanetwork.com/journals/jama/articlepdf/407629/qoa90033_378_394.pdf

[4] Perin, F., Ouyang, L., Lim, K. S., Motta, A., Maniglio, D., Moroni, L., & Mota, C. (2026). Bioprinted Constructs in the Regulatory Landscape: Current State and Future Perspectives. Advanced Materials, 38(4), e04037.

https://advanced.onlinelibrary.wiley.com/doi/full/10.1002/adma.202504037

[5] Garcia Garcia, A., Prithiviraj, S., Raina, D. B., Schmidt, T., Gonzalez Anton, S., Rabanal Cajal, L., ... & Bourgine, P. E. (2026). Engineered and decellularized human cartilage graft exhibits intrinsic immunosuppressive properties and full skeletal repair capacity. Proceedings of the National Academy of Sciences, 123(2), e2507185123.

https://www.pnas.org/doi/abs/10.1073/pnas.2507185123

[6] Gubert, S., Moon, H., Oliva, N., & Texidó, R. (2026). The osteochondral regeneration paradox: why biomimetic scaffolds are biologically superior but injectable systems dominate the clinic. RSC Advances, 16(13), 11370–11390.
https://pubs.rsc.org/en/content/articlelanding/2026/ra/d5ra09529h