Biocompatibility and integrin-mediated adhesion of human osteoblasts to poly(DL-lactide-co-glycolide) copolymers.

Abstract

The biocompatibility of polylactic acid (PLA) and polyglycolic acid (PGA) copolymers, employed in manufacturing bone-graft substitutes, is affected by their chemical composition, molecular weight and cell environment, and by the methods of polymerization and processing. Their in vitro bioactivity on human osteoblasts has been investigated very little. We first evaluated the behavior of primary human osteoblasts cultured in close contact with 75:25 and 50:50 PLA-PGA copolymers for 14 days adopting a cell culture system that allowed us to evaluate the influence of direct contact, and of factors released from polymers. The copolymers had no negative influence on cell morphology, cell viability and proliferation. Alkaline phosphatase (ALP) activity and osteocalcin production were also not affected. The initial adhesion of osteoblasts on implant surfaces requires the contribution of integrins, acting as a primary mechanism regulating cell-extracellular matrix (ECM) interactions. We observed that adhesion of osteoblasts to PLA-PGA copolymers, 2h after plating, was reduced by approximately 70% by antibodies capable to block integrin beta(1) and alpha(5)beta(1) complex and only by approximately 30% by an anti-integrin alpha(v) antibody. Therefore, beta(1) integrins may represent a predominant adhesion receptor subfamily utilized by osteoblasts to adhere to PLA-PGA copolymers. These materials do not show any negative influence on cell proliferation and differentiation.