Extending Existing Technology

Using previously tested technology platforms can accelerate the entry of any TERMP into clinical testing. Most products are combination products based on multiple technology platforms. Using one or more already-approved scaffold materials, cell-processing methods, culture media components, or transport containers greatly reduces the number of variables that need to be tested in product prototyping and preclinical testing phases. Additionally, historical data available for any technology can...

Raw Materials Testing

Cellular components of a TERMP are raw materials encompassing viable cells from the patient (autologous), other donors (allogeneic), or animals (xenogeneic). Standards Table 3.1. Overview of a potential testing program to support clinical entry of a prototypical tissue-engineered regenerative medical product (TERMP) Cellular chemistry manufacturing control Define product production and early manufacturing processes Establish cell, tissue, and biomaterial sourcing for good manufacturing...

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Foreword

Since the mid-1980s, tissue engineering has moved from a concept to a very significant field. Already we are at the point where numerous tissues, such as skin, cartilage, bone, liver, blood vessels, and others, are in the clinic or even approved by regulatory authorities. Many other tissues are being studied. In addition, the advent of human embryonic stem cells has brought forth new sources of cells that may be useful in a variety of areas of tissue engineering. This third edition of...

Three Dimensional Clinical Tissue Engineering

Yilin Cao has led a remarkable clinical tissue-engineering approach to craniofacial reconstruction in Shanghai, China. Regeneration of craniofacial bone in patients has now been reported by using demineralized bone and autologous cells. Using tissue engineering to rebuild lost bone is novel, but it is not the only regenerative medicine approach being applied to the challenge. Peptide-based therapy is an established treatment for stimulating bone formation....

Embryonic Stem Cells

ES cells and EG cells appear very similar and will likely have comparable applications in tissue engineering. In fact, recent evidence suggests that the most closely related in vivo cell type to the ES cell is an early germ cell (Zwaka and Thomson, 2005). The ES cells can self-renew, apparently without limit, in culture and are pluripotent that is, they can give rise to any cell type in the body (Amit et al., 2000 Evans and Kaufman, 1981 G. R. Martin, 1981 Shamblott et al., 1998 Thomson et al.,...

Establishing A Regulatory Pathway

Substantial clarification about appropriate regulatory pathways for evaluating TERMPs has occurred in recent years and is currently most advanced in the United States. Since several regulatory pathways exist for these products and most of the product characteristics consist of a scaffold and cells isolated from a specified source, the Office of Combination Products (OCP) serves as the most common entry point for establishing regulatory authority (21 CFR 3) (FDA, 2003). Notably, some...

Cell Sources

Both allogeneic and autologous cell sourcing have proven successful in certain tissue-engineering applications. Clinical trials have led to regulatory approval of products based on both types of sources. Among the approved living, engineered skin products, Dermagraft (Smith & Nephew) and Apligraf (Organogenesis) both utilize allogeneic cells expanded greatly from donated human foreskins to treat many unrelated patients. Despite the genetic mismatch between donor and recipient, the skin cells...

Introduction

In the early 1930s Charles Lindbergh, who was better known for his aerial activities, went to Rockefeller University and began to study the culture of organs. After the publication of his book about the culturing of organs ex vivo in order to repair or replace damaged or diseased organs, the field lay dormant for many years. Indeed, delivering respite to failing organs with devices or total replacement (transplant) became far more fashionable. Transplantation medicine has been a dramatic...

Production of TERMPs in GMP Facilities

With established product characteristics, standard operating procedures, and clinical production processes, a GMP-qualified facility can be deployed to manufacture the first clinical prototype. GMP facilities not only meet GMP guidelines, but they have specialized facility designs and highly trained personnel to produce faithfully the first clinical prototypes in a controlled and reproducible fashion. Considerations for GMP facilities include capacity limitations, availability restrictions, and...

Two Dimensional Clinical Tissue Engineering

Skin Tissue Engineering

The earliest clinical applications of tissue engineering revolved around the use of essentially flat materials designed to stimulate wound care. Tissue-engineered skin substitutes dominated the market for almost a decade. Another small and slim tissue that found a clinical application was cartilage. Later in the 1990s thin sheets of cells were produced in culture and then applied to patients using a powerful cell-sheet technology. In both the applications, engineered tissue equivalent is...

Immune Compatibility

The growing number of choices of cell sources for bio-engineered tissues opens up a range of strategies to obtain the desired cell populations. The issue of immune compatibility remains central. Although lifelong immunosup-pression can be successful, as documented by its use in conjunction with orthotopic transplantation to treat terminal organ failure, it would be preferable to design bioengi-neering-based products that will be tolerated by recipients even without immunosuppressive drugs. The...

Viireferences

Bioengineered tissues the science, the technology, and the industry. Ortho. Cranofacial Res. 8, 134-140. Ahsan, T., and Nerem, R. M. (in press). Stem cell research in regenerative medicine. In Principles of Regenerative Medicine (A. Atala, J. A. Thomson, R. M. Nerem, and R. Lanza, eds.). Elsevier Academic Press, Boston, MA. Auger, P. A., Lopez Valle, C. A., Guignard, R., Tremblay, N., Noel, B., Goulet, F., and Germain, L. (1995). Skin equivalent produced with...

Smarter Biomaterials

Scaffolds provide mechanical support and shape for neotissue construction in vitro and or through the initial period after implantation as cells expand, differentiate, and organize (Stock and Vacanti, 2001). Materials that mainly have been used to date to formulate degradable scaffolds include synthetic polymers, such as poly(L-lactic acid) (PLLA) and poly(glycolic acid) (PLGA), and polymeric biomaterials, such as alginate, chitosan, collagen, and fibrin (Langer and Tirrell, 2004). Composites...