Collagen processed with glucose and ultraviolet irradiation as an implantable biomaterial

Collagen is used as an implantable biomaterial due to its biological origin, relatively high strength for a natural material, and its ability to be processed into a variety of forms. Exposure of collagen to UV imparts crosslink formation, enhancing strength and resistance to proteolytic degradation. Concurrently, UV causes fragmentation of collagen chains, leading to denaturation of the molecule and associated loss of strength. The fragmenting and crosslinking effects of UV are caused by free radicals. In order to prevent the onset of denaturation, glucose (GLUC) was added to collagen films prior to exposure to UV in attempt to generate free-radical dependent glucose-derived crosslinks (advanced glycosylated end-products (AGEs)). The experimentation conducted was designed to investigate two hypotheses: (1) The strength and durability of surgically implanted collagen processed with ultraviolet irradiation and/or sterilized with gamma-irradiation (γ-irradiation) is enhanced by the incorporation of glucose and (2) Glucose-derived crosslinks (AGEs) are generated when glucose-incorporated collagen is exposed to ultraviolet irradiation.; The free radicals necessary for theoretically expediting AGE development were shown to be generated, but the incorporation of lysine (a potential competitive inhibitor) into the system did not limit the effects of glucose. Also, the amino acid composition did not reveal any alterations to the amino acids involved in AGE development. An AGE, pentosidine, was detected at comparable levels in collagen processed with GLUC+UV and control groups. However, there are other types of AGEs which could be present. Further specific assays for AGEs need to be conducted.; Collagen films processed with glucose and UV were significantly stronger after surgical implantation in a subcutaneous rat model compared to films processed with UV alone. Histologically, the UV and GLUC+UV film groups exhibited comparable cellular responses. The stabilizing effects of glucose on the physical properties of collagen sterilized with γ-irradiation were apparent both in vivo and in vitro. Surgically implanted GLUC+UV+γ films were significantly stronger and more durable than UV+γ films. Additionally, GLUC+γ collagen films were more durable than CONT+γ films. Processing collagen-based materials with glucose and UV, with or without sterilization by γ-irradiation, may be an attractive method for processing materials for surgical applications.