DOPA-derived electroactive copolymer and IGF-1 immobilized poly(lactic-co-glycolic acid)/hydroxyapatite biodegradable microspheres for synergistic bone repair

Abstract

Abstract Owing to defect features (irregular shape and size) and local environments (e.g., pulsation of dura matter and proximity of the brain), the skull is one of the most difficult to repair. Electroactive microsphere systems with good injectability, adjustable size, high surface-to-volume ratio and surface modifiability, exhibit excellent bone regeneration potential. Herein, the electroactive microspheres were prepared by immobilizing aniline tetramer (AT) on poly(lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) microspheres. Subsequently, the 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth-factor-1 (DOPA-IGF-1) inspired by bioorthogonal chemistry was designed by combining the recombinant DNA technology and tyrosinase treatment, and modified on electroactive scaffolds surface. The as-prepared microspheres exhibited excellent sphericity and homogeneity with an average diameter of 329.2 ± 16.5 μm. Interestingly, the electroactive microsphere exhibits significant cell proliferation and enhanced osteogenic differentiation, and combining with DOPA-IGF-1 can further synergistically induce mineralization and osteogenic differentiation. Rat calvarial defect repair experiments showed excellent repairability in forming mineralized collagen deposition within the transplanted composite microspheres scaffold in the bone defect site. Thus, biomimetic composite microsphere with electroactivity and bioactivity exhibits considerable potential for calvarial defect repair.