State of the Art of Clinical Applications of Tissue Engineering in 2021

Tissue engineering (TE) was introduced almost 30 years ago as a potential technique for regenerating human tissues. However, despite promising laboratory findings, the complexity of the human body, scientific hurdles, and lack of persistent long-term funding still hamper its translation toward clinical applications. In this report, we compile an inventory of clinically applied TE medical products relevant to surgery. A review of the literature, including articles published within the period from 1991 to 2020, was performed according to the PRISMA protocol, using databanks PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov. We identified 1039 full-length articles as eligible; owing to the scarcity of clinical, randomized, controlled trials and case studies, we extended our search toward a broad surgical spectrum. Forty articles involved clinical TE studies. Among these, seven were related to TE protocols for cartilage applied in the reconstruction of nose, ear, and trachea. Nine articles reported TE protocols for articular cartilage, nine for urological purposes, seven described TE strategies for cardiovascular aims, and eight for dermal applications. However, only two clinical studies reported on three-dimensional (3D) and functional long-lasting TE constructs. The concept of generating 3D TE constructs and organs based on autologous molecules and cells is intriguing and promising. The first translational tissue-engineered products and techniques have been clinically implemented. However, despite the 30 years of research and development in this field, TE is still in its clinical infancy. Multiple experimental, ethical, budgetary, and regulatory difficulties hinder its rapid translation. Nevertheless, the first clinical applications show great promise and indicate that the translation toward clinical medical implementation has finally started. Impact statement The clinical use of a tissue-engineered windpipe in compassionate patients elicited euphoria in the media between 2010 and 2016: tissue engineering (TE) had proven to be no longer a fictional concept but a life-saving reality. However, most of the treated patients died, and the surgeon was convicted for scientific misconduct and aggravated assault. As of 2020, the authors had eight of their articles retracted and two received an expression of concern.¹ These events have fueled skepticism among clinicians about TE: science or fiction? Although TE is full of promises, it is not realistic yet to engineer a (vascularized) construct that thrives in a "hostile" clinical environment. Therefore, a realistic update of the current clinical outcomes and the promises of TE in human trials are essential.