Because of an aging population and increased occurrence of sports-related injuries, musculoskeletal disorders have become one of the major health concerns in the United States. Current treatments, although fairly successful, do not provide the optimum therapy. These treatments typically rely on donor tissues obtained either from the patient or from another source. The former raises the issue of supply, whereas the latter poses the risk of rejection and disease transfer. This has prompted orthopedic surgeons and scientists to look for viable alternatives. In recent years, tissue engineering has gained increasing support as a method to treat orthopedic disorders. Because it uses principles of engineering, biology, and chemistry, tissue engineering may provide a more effective approach to the treatment of musculoskeletal disorders than traditional methods. This chapter presents a review of current methods and new tissue-engineering techniques for the treatment of disorders affecting bone, ligament, and cartilage.

The hydrolytically unstable polyphosphazenes, poly [(imidazolyl) (methylphenoxy) phosphazenes] and poly [ethyl glycinato) (methylphenoxy) phosphazenes], were studied as potential polymeric supports for cells in tissue regeneration. For bone repair, their specific function would be to support osteoblast growth, forming a bone-polymer matrix. MC3T3-E1 cells (an osteogenic cell line) were seeded onto polymer matrices and cell adhesion and growth as well as polymer degradation were examined. Both imidazolyl- and ethyl glycinato-substituted polyphosphazenes supported the growth of MC3T3-E1 cells. An increase in the content of the imidazolyl side group resulted in a reduction in cell attachment and growth on the polymer surface and an increase in the rate of degradation of the polymer. In contrast, substitution with the ethyl glycinato group favored increased cell adhesion and growth and also an increase in the rate of degradation of the polymers. Thus, the polyphosphazenes represent a system whereby cell growth and degradation can be modulated by varying the nature of the hydrolytically unstable side chain. This in vitro evaluation suggests that the polyphosphazenes may be suitable candidate biomaterials for the construction of a cell-polymer matrix for tissue regeneration.

Current methods for the replacement of skeletal tissue in general involve the use of autografts or allografts. There are considerable drawbacks in the use of either of these tissues. In an effort to provide an alternative to traditional graft materials, a degradable 3-dimensional (3-D) osteoblast cell-polymer matrix was designed as a construct for skeletal tissue regeneration. A degradable amino acid containing polymer, poly[(methylphenoxy)(ethyl glycinato) phosphazene], was synthesized and a 3-D matrix system was prepared using a salt leaching technique. This 3-D polyphosphazene polymer matrix system, 3-D-PHOS, was then seeded with osteoblast cells for the creation of a cell-polymer matrix material. The 3-D-PHOS matrix possessed an average pore diameter of 165 microns. Environmental scanning electron microscopy revealed a reconnecting porous network throughout the polymer with an even distribution of pores over the surface of the matrix. Osteoblast cells were found attached and grew on the 3-D-PHOS at a steady rate throughout the 21-day period studied in vitro, in contrast to osteoblast growth kinetics on similar, but 2-D polyphosphazene matrices, that showed a decline in cell growth after 7 days. Characterization of 3-D-PHOS osteoblastpolymer matrices by light microscopy revealed cells growing within the pores as well as on surface of the polymer as early as day 1. This novel porous 3-D-PHOS matrix may be suitable for use as a bioerodible scaffold for regeneration of skeletal tissue.

Biomaterials based on the polymers of lactic acid and glycolic acid and their copolymers are used or studied extensively as implantable devices for drug delivery, tissue engineering and other biomedical applications. Although these polymers have shown good biocompatibility, concerns have been raised regarding their acidic degradation products, which have important implications for long-term implantable systems. Therefore, we have designed a novel biodegradable polyphosphazene/poly(a-hydroxyester) blend whose degradation products are less acidic than those of the poly(a-hydroxyester) alone. In this study, the degradation characteristics of a blend of poly(lactide-co-glycolide) (50 : 50 PLAGA) and poly[(50% ethyl glycinato)(50% p-methylphenoxy) phosphazene] (PPHOS-EG50) were qualitatively and quantitatively determined with comparisons made to the parent polymers. Circular matrices (14 mm diameter) of the PLAGA, PPHOS-EG50 and PLAGA-PPHOS-EG50 blend were degraded in nonbuffered solutions (pH 7.4). The degraded polymers were characterized for percentage mass loss and molecular weight and the degradation medium was characterized for acid released in non-buffered solutions. The amounts of neutralizing base necessary to bring about neutral pH were measured for each polymer or polymer blend during degradation. The poly(phosphazene)/poly(lactideco-glycolide) blend required significantly less neutralizing base in order to bring about neutral solution pH during the degradation period studied. The results indicated that the blend degraded at a rate intermediate to that of the parent polymers and that the degradation products of the polyphosphazene neutralized the acidic degradation products of PLAGA. Thus, results from these in vitro degradation studies suggest that the PLAGA-PPHOS-EG50 blend may provide a viable improvement to biomaterials based on acid-releasing organic polymers. r

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