Issues with Tissues: Trends in Tissue-Engineered Products in Clinical Trials in the European Union.

Tissue-engineered products (TEPs) consist of engineered cells or tissues produced to regenerate, repair, or replace a dysfunctional, diseased, or absent human tissue. TEPs make up <5% of all advanced therapeutic medicinal products (ATMPs) in clinical trials and received 5.1% of ATMP-designated funding in trials in the European Union (EU) in 2019, highlighting the relatively low proportion of TEPs being developed. The realization of TEPs being marketed has yet to be fulfilled, with few products being approved. Since 2009, 90 TEP-based clinical trials have been undertaken in the EU. Of these 90, 25 were Phase I/II trials, 35 were Phase II, 28 were Phase III, and two were Phase IV trials. This review provides an overview of TEPs in development, identifying musculoskeletal, cardiovascular, and skin/connective tissue disorders as the main therapeutic areas of interest. Commercial sponsors have funded most trials, and a significantly higher proportion of late-phase trials. Furthermore, this study has identified a shift toward the use of allogeneic cells in TEPs and increased activity in the proportion of early phase trials listed. This indicates a renewed interest in TEP development as sponsors adapt to the new regulation, with prospects of more TEP market authorization applications in the future. Impact Statement Tissue-engineered products (TEPs) consist of engineered cells or tissues produced to regenerate, repair, or replace a dysfunctional, diseased, or absent human tissue. This article evaluates the regulatory landscape of TEPs and identifies the trends in clinical trial activity in the European Union (EU) since the introduction of Regulation (EC) No 1394/2007. This article identifies trends in TEP development, highlighting the most active member states, commercial involvement, a shift toward the use of allogeneic cells and a renewed interest in TEP development in recent years.

Xenotransplantation of decellularized pig heart valves-Regulatory aspects in Europe.

BACKGROUND: The lack of human donors for allotransplantation forces the development of other strategies to circumvent the existing organ shortage documented on the waiting lists. Here, xenotransplantation offers a suitable option since the genetic modification of animals has become an established method that allows the generation of animals as donors of cells, tissues, and organs with reduced antigenicity. METHODS: Focus is given on the generation of decellularized matrix scaffolds, for example, for valve transplantation and/or repair, that have the potential being fully assimilated by the recipient as they are no longer a mechanical implant with risk of calcification and related failure. RESULTS: This new class of products is transplants that will be regulated either as medical devices or as cell-based medicinal products, that is, advanced therapy medicinal products, according to the regulations in the European Union. CONCLUSIONS: In this review, we compile relevant regulatory aspects and point out the possibilities of how these products for human use may be regulated in the future.

Tissue engineering-relevant characteristics of ex vivo and monolayer-expanded chondrocytes from the notch versus trochlea of human knee joints.

PURPOSE: The aim was to analyse the biological characteristics of chondrocytes from the two biopsy sites notch vs. trochlea of human knee joints. The question was whether tissue engineering-relevant characteristics such as viability and mRNA expression profile would be comparable ex vivo and after monolayer expansion, as these are parts of routine autologous chondrocyte implantation (ACI). METHODS: Biopsies from the intercondylar notch and the lateral aspect of the trochlea from 20 patients with ICRS grades 3 and 4 cartilage defects were harvested during arthroscopy. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. RESULTS: Compared with notch chondrocytes, ex vivo trochlea chondrocytes had comparable cell numbers, vitality and aggrecan, collagen types 1, -2 and -10 mRNA expression. After monolayer expansion both notch and trochlea chondrocyte characteristics were comparably altered, regardless of their biopsy origin, and no significant differences in viability and mRNA expression were noted. CONCLUSIONS: Collectively, these findings suggest that tissue engineering-relevant characteristics of notch and trochlea chondrocytes are comparable ex vivo and after monolayer expansion. Thus, trochlea chondrocytes promise clinical potential and chondrocytes for ACI could potentially be generated from both notch and trochlea biopsy sites.