Accelerated Angiogenic Host Tissue Response to Poly(L-Lactide-co-Glycolide) Scaffolds by Vitalization with Osteoblast-like Cells

Abstract

Bone substitutes should ideally promote rapid vascularization, which could be accelerated if these substitutes were vitalized by autologous cells. Although adequate engraftment of porous poly(L-lactide-co-glycolide) (PLGA) scaffolds has been demonstrated in the past, it has not yet been investigated how vascularization is influenced by vitalization or, more precisely, by seeding PLGA scaffolds with osteoblast-like cells (OLCs). For this reason, we conducted an in vivo study to assess host angiogenic and inflammatory responses after the implantation of PLGA scaffolds vitalized with isogeneic OLCs. OLCs were seeded on collagen-coated PLGA scaffolds that were implanted into dorsal skinfold chambers in BALB/c mice (n = 8). Two further groups of animals received either collagen-coated (n = 8) or uncoated PLGA scaffolds (n = 8). Animals that received chambers without implants served as controls (n = 8). Angiogenesis, neovascularization, and leukocyte-endothelial cell interaction were analyzed for 14 days using intravital fluorescence microscopy. PLGA scaffolds with and without OLCs showed a temporary increase in leukocyte recruitment. At day 3 after implantation, a marked angiogenic host tissue response was observed in close vicinity of all scaffolds studied. At days 6 and 10, the angiogenic response was significantly higher (p < 0.05) in PLGA scaffolds vitalized with OLCs than in uncoated or collagen-coated PLGA scaffolds. The majority of OLCs, however, died within 14 days after implantation. Our study demonstrates that PLGA scaffold vitalization with OLCs accelerates the angiogenic response in the surrounding host tissue. Bone substitutes created by tissue engineering may thus be superior to nonvitalized substitutes although the seeded cells do not survive for long periods.