Ectopic bone formation in and soft-tissue response to P(CL/DLLA)/bioactive glass composite scaffolds

Abstract

Objectives: To characterize biological response to subcutaneously implanted macroporous poly(ε-caprolactone/D,L-lactide)-based scaffolds, and to evaluate the effect of bioactive glass (BAG) filler and osteogenic cells to the tissue response and ectopic bone formation.

Material and methods: In the first part of this study, six different scaffold types were screened in a rat subcutaneous implantation model. The polymer scaffolds with 70/30 caprolactone/lactide ratio and corresponding composites with < 45 μm BAG filler size were chosen for the further ectopic bone formation assay. The scaffolds were loaded with differentiating bone marrow stromal cells and implanted subcutaneously in syngeneic rats.

Results: With plain scaffolds, only mild foreign body reaction with no signs of gross inflammation was observed after 4 weeks of implantation. Furthermore, the scaffolds were fully invaded by well-vascularized soft connective tissue. Overall, all the tested scaffold types showed an appropriate host response. With cell-seeded scaffolds, several loci of immature mineralizing tissue and small amounts of mature bone were observed after 4 weeks. The incidence of mature bone formation was two and four in polymer scaffolds and composites, respectively (n = 8). After twelve weeks, mature bone was observed in only one polymer scaffold but in seven composites (n = 8). Excluding bone formation, the host response was considered similar to that with cell-free scaffolds.

Conclusions: Plain scaffolds supported the ingrowth of well-vascularized fibroconnective tissue. Furthermore, cell seeded composites with BAG filler showed enhanced ectopic bone formation in comparison with corresponding neat polymer scaffolds.

Keywords: bioactive glass; bone tissue engineering; composite; copolymer; scaffold.