Multi-component PLGA microcapsules system for temporal control in bone regeneration: regulating release timing and rate

To address the clinical challenge of repairing critical-sized bone defects, an increasing number of sustained-release scaffolds loaded with bioactive components are being developed. Drug encapsulation within the scaffold is a favored loading method, as mutual reactions are avoided before drug release. However, issues such as severe initial burst release, inappropriately timed release, and short drug-release duration remain unresolved. We report a customizable PLGA-based microcapsule scaffold engineered for the sequential and spatiotemporally controlled release of minocycline, VEGF-A, and BMP-2. By tailoring the degradation kinetics of the microcapsules and pore structure that develops during the degradation process, precise control over multi-phase drug delivery was achieved. An in vitro sustained-release experiment demonstrated the scaffold’s ability to control the release of encapsulated active ingredients over various time periods, successfully sustaining the release of growth factors for approximately 60 days. Further experimental findings clearly indicated the scaffold’s excellent biocompatibility and biodegradability. Early-phase extracts exhibited potent antibacterial activity, mid-phase extracts promoted angiogenesis, and late-phase extracts significantly enhanced osteogenic differentiation. In a mouse model, this scaffold facilitated bone regeneration with enhanced vascularization, as confirmed by micro-CT and histological analyses. These findings highlight a promising strategy for engineering multifunctional scaffolds with programmed release capabilities for bone tissue repair.