Bone defects resulting from aging and trauma necessitate effective bone grafts and substitutes. While allografts and autografts offer three-dimensional templates, limitations in availability drive the development of synthetic alternatives. Inorganic materials, though bioactive, lack toughness, while polymers, though tough and biodegradable, are often bioinert. Composite materials face challenges like inhomogeneous biodegradation and non-biointeractive surfaces due to weak bonding between organic and inorganic phases. To address these limitations, inorganic-organic hybrids covalently bonded via silica networks have emerged. However, many biodegradable hybrids suffer from long gelation times, hindering the creation of porous scaffolds. This research aimed to develop a biodegradable PU-silica hybrid with a rapid sol-gel transition for fabricating porous bone regenerative scaffolds.

Numerous studies have explored inorganic-organic hybrids for bone regeneration, utilizing polymers copolymerized with silane coupling agents like GPTMS and TMSPMA to form conetworks with silica matrices via sol-gel processes. However, most biodegradable hybrids require extensive gelation times (days or even weeks), limiting their use in creating porous scaffolds. Previous research predominantly resulted in cylindrical shapes due to the lengthy gelling and drying stages inherent in these techniques.

A biodegradable polyurethane (PU) was synthesized using PCL-diol, hexamethylene diisocyanate (HDI), and (3-aminopropyl)triethoxysilane (APTES). The APTES functionalization enabled covalent bonding to the silica network during the sol-gel process. The thermoplastic nature of the PU, facilitated by PCL-diol and aliphatic HDI, ensured solubility in solvents compatible with the silica precursor (hydrolyzed TEOS), preventing phase separation. Allophanate bond formation during high-temperature prepolymer synthesis increased the number of exposed functional groups, significantly shortening the gelation time. Hybrids with varying silica ratios (0, 10, 20, and 30 wt.%) were prepared. The rapid gelation allowed for the fabrication of 3D porous scaffolds using a salt-leaching method. The shape memory ability of the scaffolds, stemming from the chemically cross-linked crystalline PCL backbone, was noted. A rat distal condyle defect model was used to evaluate bone regeneration, employing histological evaluation, micro-computed tomography (µCT), and immunostaining for markers of inflammation, angiogenesis, and osteogenic differentiation.

The synthesized PU successfully incorporated APTES, confirmed by H-NMR. Allophanate bond formation, indicated by FTIR, increased the molecular weight and number of silane groups. Rheology measurements showed remarkably short gelation times (80-520 s) for the hybrids, compared to previous studies requiring days. FTIR and TGA confirmed the presence of both polymer and silica components in the hybrids, with the thermal stability enhanced by siloxane bonding. DSC analysis revealed that while crystallinity was relatively unchanged at 0% and 10% silica, it decreased significantly at 20% and 30% silica. The mechanical properties of the scaffolds were significantly improved by silica addition, with the 30 wt.% scaffold showing optimal strength. The 3D porous structure was successfully fabricated via salt-leaching method, providing high surface area for cell interaction. In vivo studies in a rat model demonstrated that the hybrid scaffold, particularly the 30 wt.% silica composition, promoted bone regeneration, evidenced by histological analyses, µCT showing bone mineralization, and immunostaining indicating successful angiogenesis and osteogenic differentiation.

The rapid sol-gel transition achieved in this study offers a significant advancement in the fabrication of biodegradable inorganic-organic hybrid scaffolds for bone repair. The allophanate bonding strategy effectively shortened the gelation time, overcoming a major limitation of previous approaches. The resulting 3D porous scaffolds with tailored mechanical properties and shape memory capability are well-suited to addressing irregular bone defects. The in vivo data strongly supports the potential of these hybrids for enhanced bone regeneration, highlighting the synergistic effects of the inorganic and organic components.

This study successfully demonstrated the synthesis and application of tough, biodegradable PU-silica hybrids with a rapid sol-gel transition for bone tissue engineering. The optimized 30 wt.% silica hybrid scaffold showed promising mechanical properties and effectively promoted bone regeneration in a rat model. Future research could explore different silica precursors, polymer compositions, and pore architectures to further enhance the efficacy and versatility of these scaffolds for diverse bone regeneration applications.

The current study primarily focused on a rat model. Further investigation is needed to validate these findings in larger animal models and ultimately in human clinical trials. Long-term biodegradation and potential inflammatory responses in vivo warrant further examination.