Butterfly metamorphosis inspired injectable in situ forming scaffolds with time-dependent pore formation for bone regeneration

Preformed three-dimensional scaffolds with insufficient mechanical properties, poor surgical performance, and morphological mismatch to defects with irregular shape have shown drawbacks in animal evaluations and clinical applications. This motivates the development of novel injectable systems to ideally fill bone defects, allowing in situ solidification within the host tissues while retaining high initial mechanical strength and appropriate porosity. In this study, an in situ forming scaffold with time-dependent pore formation inspired by the metamorphosis of a butterfly was fabricated by incorporating gelatin microspheres (GMs) into a poly(lactic-co-glycolic acid) (PLGA)-based injectable implant. After optimizing solvent, molecular weight and solution concentration of PLGA matrix, the injectable mixture could be easily injected into both aqueous solution and random-shaped grooves while in situ solidified instantaneously. The injectability enabled an in situ morphological match within an irregular bone defect, providing high initial strength in the early period. The toughness of the injectable implant also allowed them to be easily bent into a ring without breaking. Time-dependent pore formation was accomplished by gradual degradation of GMs, generating appropriate space for tissue ingrowth in the scaffold. It is expected that the injectable in situ forming implant would aid the bone healing process by maintaining initial mechanical support and creating a spatiotemporally evolutionary microstructure during bone tissue regeneration.