Incorporating Bone‐Derived ECM into Macroporous Microribbon Scaffolds Accelerates Bone Regeneration

Tissue-derived extracellular matrix (tdECM) hydrogels serve as effective scaffolds for tissue regeneration by promoting a regenerative immune response. While most tdECM hydrogels are nanoporous and tailored for soft tissue, macroporosity is crucial for bone regeneration. Yet, there's a shortage of macroporous ECM-based hydrogels for this purpose. The study aims to address this gap by developing a co-spinning technique to integrate bone-derived ECM (bECM) into gelatin-based, macroporous microribbon (µRB) scaffolds. The effect of varying doses of bECM on scaffold properties was characterized. In vitro studies revealed 15% bECM as optimal for promoting MSC osteogenesis and macrophage (Mφ) polarization. When implanted in a mouse critical-sized cranial bone defect model, 15% bECM with tricalcium phosphate (TCP) microparticles significantly accelerated bone regeneration and vascularization, filling over 55% of the void by week 2. Increasing bECM to 25% enhanced mesenchymal stem cell (MSC) recruitment and decreased M1 Mφ polarization but reduced overall bone formation and vascularization. The findings demonstrate co-spun gelatin/bECM hydrogels as promising macroporous scaffolds for robust endogenous bone regeneration, without the need for exogenous cells or growth factors. While this study focused on bone regeneration, this platform holds the potential for incorporating various tdECM into macroporous scaffolds for diverse tissue regeneration applications.