The advanced therapy classification procedure. Overview of experience gained so far.

The classification procedure, introduced by the European Regulation on advanced therapy medicinal products (ATMPs), has received a tremendous interest from companies, academic and public sponsors developing ATMPs. This procedure gives companies the opportunity to verify whether or not the product they are developing can be considered an ATMP and can therefore benefit from the new regulatory pathway introduced in the European Union for these types of medicinal products. This procedure is optional, free of charge and may take place at any stage of the development of an ATMP in advance of applying for a marketing authorisation. In case of doubt, briefing meetings organised by the European Medicines Agency Innovation Task Force may help preparing for an ATMP classification and are a starting point for the interactions between the Agency and the developers of ATMPs. This article reviews the advantages of the classification procedure for both the developers of ATMPs and the European regulatory network. Since the introduction of this procedure and up to 10 November 2010, the Committee for Advanced Therapies (CAT) has finalised 38 applications for classification.

Activated hyaluronic acid/collagen composite hydrogel with tunable physical properties and improved biological properties.

Self-crosslinkable and injectable hydrogels were fabricated with collagen type I (Col I) and N-hydroxy sulfosuccinimide activated hyaluronic acid (HA-sNHS) at physiological conditions without any initiators or crosslinkers. The physical properties of hydrogels, such as gelation time, swelling property, degradation property and mechanical property could be regulated by adjusting the substitution degree (DS) of HA-sNHS. Chondrocytes were encapsulated into hydrogels and their proliferation, phenotype maintenance and matrix secretion were characterized. The results demonstrated that chondrocytes in hydrogel Col I/HA-sNHS32% in which the DS of HA-sNHS was 32% secreted more cartilage specific matrix than others. The results of animal experiment demonstrated that hydrogels Col I and Col I/HA-sNHS32% both had good biodegradability and cytocompatibility. This study provided a novel and simple method for fabrication of self-crosslinkable and injectable hydrogels with tunable physical properties. It implied that these hydrogels could find some applications in the fields of cell encapsulation and tissue engineering.

[Clinical regenerative medicine: the skin].

Tissue engineering of skin is classified into acellular artificial skin and cellular artificial skin. Acellular artificial skin or artificial dermis, is composed of an inner collagen sponge and an outer silicone film. When placed on wounds, the collagen sponge is spontaneously converted into a dermis-like connective tissue. Addition of bFGF or cultured fibroblasts accelerates synthesis of the dermis-like tissue. Cultured epidermis often fails to take on a full-thickness skin defect because of lack of dermal component. Cultured skin with both epidermal and dermal components seems to be an ideal skin substitute, but its take rate is still low. Regeneration of complete skin with skin appendages, vascular networks, elastic fibers and so on is desired.

Bioengineered tissues: the science, the technology, and the industry.

OBJECTIVE: The bioengineering of tissues and organs, sometimes called tissue engineering and at other times regenerative medicine, is emerging as a science, as a technology, and as an industry. The goal is the repair, replacement, and/or the regeneration of tissues and organs. The objective of this paper is to identify and discuss the major issues that have become apparent. RESULTS: One of the critical issues is that of cell source, i.e. what will be the source of the cells to be employed? Another critical issue is the development of approaches for the fabrication of substitute tissues/organs and/or vehicles for the delivery of biological active molecules for use in the repair/regeneration of tissues. A third critical issue, one very much related to cell source, is that of immune acceptance. In addition, there are technological hurdles; there are additional issues such as the scale-up of manufacturing processes and the preservation of living-cell products for off-the-shelf availability. Although the initial products have been superficially applied skin substitutes, as this fledgling industry continues to evolve, it is beginning to focus on a wider range of more invasive and complicated products. From a public health perspective, the real opportunity may be in addressing chronic diseases, as well as the transplantation crisis (i.e. the tremendous disparity between patient need for vital organs and donor availability) and, equally important is the challenge of neural repair. CONCLUSION: These are the grand challenges, and the scientific community, business/private sector, and federal government must mobilize itself together in this emerging area to translate the benchtop science to the patient bedside.