Physiological Cultured Skin Substitutes for Wound Healing
- PDF / 2,217,309 Bytes
- 8 Pages / 420.48 x 639 pts Page_size
- 73 Downloads / 186 Views
PHYSIOLOGICAL CULTURED SKIN SUBSTITUTES FOR WOUND HEALING
Craig Halberstadt, Phil Anderson, Ronnda Bartel, Ron Cohen and Gail Naughton Advanced
Tissue Sciences, La Jolla, CA
ABSTRACT Physiological dermal and dermal-epidermal skin analogs have been developed in our laboratory using a novel technology for three-dimensional tissue culture. Human neonatal dermal fibroblasts are seeded on a biodegradable mesh made of polyglycolic or polyglactic acid (PGAIPGL). As the fibroblasts proliferate, they stretch across the mesh openings and secrete growth factors and human dermal matrix proteins, including collagen types I & HI and elastin. This process forms a metabolically active, three-dimensional dermal tissue around the mesh scaffolding. The mesh fibers are hydrolyzed over time and is completely resorbed in vivo within four to eight weeks. Multiple sheets of the PGA/PGL-dermal analog are grown simultaneously in a closed, continuous media-flow system, also developed in our laboratory. After attaining confluence, the dermal sheets may be seeded with keratinocytes, to create a living dermal-epidermal composite tissue. Pre-clinical studies in mini-pigs and athymic mice have shown that the dermal analog "takes" and vascularizes rapidly in full-thickness wounds, and provides a viable dermal base for both meshed split-thickness skin grafts and cultured keratinocyte sheets. There has been no evidence of rejection. The dermal analog is now being studied clinically beneath thin meshed skin autografts in patients with severe bums. In vivo pre-clinical studies of the dermalepidermal composite, as a complete skin replacement, are also in progress. This technology has potential for applications in severe burns and other full-thickness skin injuries.
INTRODUCTION Many advances have taken place in the culture of cells in vitro, including the development of appropriate medium formulations (serum and serum-free) (1-5) and the design of reactor systems for the long-term growth of cells (6-9). The major emphasis in growing mammalian cells has been for the production of proteins. However, there is increasing interest in the growth of mammalian cells for the formation of tissues such as skin, liver and bone marrow (10-16). Through the development of reactor systems and a better understanding of mammalian cell biology, the growth of cells to tissue-like densities has become feasible (6-9, 17). Various approaches have been used for the growth of high cell density cultures, including: hollow fiber reactors (18-22), microencapsulation (23-26), fluidized bed reactors (27) and membrane bioreactors (28). All of these systems have advantages and disadvantages for the growth of cells to tissue-like densities. However, with the exception of microencapsulation, none of these systems has been designed to grow tissues for the purposes of in vivo transplantation. An optimal system for this purpose would grow the tissue individually in a self-contained system, and allow cryopreservation and/or transport of the resulting tissue to the patient without ever
Data Loading...
