Optimizing the bio-degradability and biocompatibility of a biogenic collagen membrane through cross-linking and zinc-doped hydroxyapatite

Abstract

Biogenic collagen membranes have been widely used as soft tissue barriers in guided bone regeneration (GBR) and guided tissue regeneration (GTR). Nevertheless, their clinical performance remains unsatisfactory because of their low mechanical strength and fast degradation rate in vivo. Although cross-linking with chemical agents is effective and reliable for prolonging the degradation time of collagen membranes, some adverse effects including potential cytotoxicity and undesirable tissue integration have been observed during this process. As a fundamental nutritional trace element, zinc plays an active role in promoting the growth of cells and regulating the degradation of the collagen matrix. Herein, a biogenic collagen membrane was cross-linked with glutaraldehyde-alendronate to prolong its degradation time. The physiochemical and biological properties were enhanced by the incorporation of zinc-doped nanohydroxyapatite (nZnHA), with the native structure of collagen preserved. Specifically, the cross-linking combined with the incorporation of 1% and 2% nZnHA seemed to endow the membrane with the most appropriate biocompatibility and tissue integration capability among the cross-linked membranes, as well as offering a degradation period of six weeks in a rat subcutaneous model. Thus, improving the clinical performance of biogenic collagen membranes by cross-linking together with the incorporation of nZnHA is a promising strategy for the improvement of biogenic collagen membranes. Statement of significance: The significance of this research includes: • We fabricated a cross-linked collagen membrane with enhanced mechanical properties, prolonged degradation time and uncompromised biocompatibility by GA-alendronate cross-linking and nZnHA doping. • Tuning the incorporation concentration of zinc ions can effectively manipulate the biocompatibility and degradation process of the membrane fabricated. • We proposed a promising strategy to improve the clinical performance of biogenic collagen membranes by cross-linking together with the incorporation of nZnHA.