Tough and biodegradable polyurethane-silica hybrids with a rapid sol-gel transition for bone repair

Bone defects from aging and trauma drive a growing need for grafts and substitutes. Autografts/allografts are limited by donor site availability and quantity. Synthetic options (bioceramics, polymers, composites) each have drawbacks: inorganic materials are bioactive but brittle; polymers are tough and biodegradable but bioinert; composites suffer macroscale phase separation due to weak organic–inorganic bonding, leading to crack propagation, loss of mechanical properties, and masked bioactivity. Inorganic–organic hybrids that covalently connect polymers to silica networks via sol–gel chemistry have emerged to overcome these issues. However, many biodegradable hybrids exhibit long gelation times, hindering fabrication of porous bone scaffolds. This study aims to create a biodegradable polyurethane–silica hybrid with rapid sol–gel transition, robust mechanics, and biological activity suitable for porous bone-regenerative scaffolds. The hypothesis is that incorporating organoalkoxysilane (APTES) into a PCL-based PU and leveraging allophanate formation will increase crosslinking points to accelerate gelation, enable shape memory behavior, and promote osteogenesis and angiogenesis for bone repair.

Prior work has explored inorganic–organic hybrids by incorporating silane coupling agents (e.g., GPTMS, TMSPMA) into polymers to form conetworks with silica via sol–gel processing, improving interfacial bonding compared to conventional composites. Nonetheless, many biodegradable hybrids require days to weeks to gel, restricting scaffold geometries (often cylinders) due to prolonged gelling/drying and risk of cracking from capillary stresses. Weak organic–inorganic interactions in composites lead to phase separation, compromised mechanics, and reduced bioactivity. Silica condensation under acidic conditions can be slow, further extending gelation times. There remains a need for biodegradable hybrids with strong covalent coupling and rapid gelation to enable facile fabrication of 3D porous scaffolds with enhanced bioactivity for bone regeneration.

- Polymer synthesis: A biodegradable polyurethane was synthesized using PCL-diol (polyol), hexamethylene diisocyanate (HDI), and (3-aminopropyl)triethoxysilane (APTES) at 90 °C in toluene with Sn(Oct)2 catalyst under vacuum/argon. PCL-diol reacted with HDI to form urethane bonds; subsequent reaction with APTES introduced alkoxysilane functionality onto the polymer chains. High reaction temperature induced secondary allophanate formation, increasing branching and the number of exposed silane groups. Polymers with varying APTES feed ratios were prepared; composition and molecular weights were analyzed by 1H NMR and GPC. - Hybrid formation (sol–gel): Tetraethyl orthosilicate (TEOS) was hydrolyzed to Si(OH)4 under acidic conditions. The alkoxysilane-functionalized PU was mixed prior to condensation, enabling siloxane bond formation (Si–O–Si) between polymer-bound APTES and silica, yielding covalently bonded inorganic–organic hybrids. Hybrids were prepared with target silica contents of 0, 10, 20, and 30 wt.% (BPH0, BPH10, BPH20, BPH30). - Scaffold fabrication: Rapid sol-to-gel transition enabled fabrication of 3D porous hybrid scaffolds via a simple salt-leaching process. Scaffolds are denoted BPHS with corresponding silica content. - Physicochemical characterization: Rheometry monitored gelation by tracking storage (G′) and loss (G″) moduli and their crossover times. FTIR assessed chemical bonding (polymer C=O/C–O and silica Si–O–Si bands). TGA measured residual inorganic content and thermal stability; DSC assessed melting temperature and crystallinity in bulk (BPH) and porous scaffold (BPHS) forms, before/after annealing. - Comparative control: A PCL–silica composite lacking organoalkoxysilane functionality was assessed for gelation behavior. - In vivo evaluation: Rat distal condyle defect model used to assess bone regeneration with hybrids at different silica ratios. Outcomes included histology (cell types in new bone), micro-computed tomography (µCT) for mineralization, and immunostaining for markers of inflammation, angiogenesis, and osteogenic differentiation.

- Successful synthesis of APTES-functionalized PCL-based PU confirmed by 1H NMR (characteristic peaks for PCL, HDI, APTES) and evidence of allophanate linkages (FTIR C=O stretching), indicating secondary reactions at 90 °C that increased molecular weight and silane group content. - Rapid gelation: Hybrid gelation occurred within 10 minutes due to increased crosslinking points from APTES and allophanate branching. Rheology crossover (G′=G″) times: BPH0 (no silica) 520 s; BPH10 80 s; BPH20 240 s; BPH30 330 s. In contrast, a PCL–silica composite without organoalkoxysilane remained a sol after 1 h. Reported biodegradable hybrids in literature often required 1–2 weeks to gel. - Chemical structure: FTIR showed decreasing hydrocarbon absorptions and increasing silica Si–O–Si bands (798–1094 cm−1) with higher inorganic content, confirming hybrid network formation. - Inorganic content and thermal stability: TGA residual masses matched targeted silica contents (approx. 5.2, 8.1, 21.7, and 30 wt.% for BPH0, BPH10, BPH20, BPH30, respectively). PU alone decomposed at 285–410 °C; hybrids decomposed at higher temperatures (370–500 °C), indicating enhanced thermal stability from siloxane bonding and silica’s insulating effect. - Thermal transitions and crystallinity: Silica reduced melting temperatures; porous scaffolds (BPHS) showed reduced crystallinity compared to bulk (BPH). Crystallinity (%): BPH0 28.84, BPH10 29.63; BPHS0 21.83, BPHS10 23.66. For higher silica contents: BPH20 10.65, BPH30 4.74; BPHS20 0.99, BPHS30 1.61, indicating substantial suppression of crystallinity in porous hybrids with ≥20 wt.% silica. - Mechanical/process implications: The rapid sol–gel transition enabled fabrication of 3D porous scaffolds via simple salt-leaching and potentially other methods (e.g., 3D printing). The 30 wt.% silica hybrid scaffold best balanced thermal stability and mechanical integrity and resisted thermal deformation. - Functional properties and bioactivity: Hybrids were flexible, fully biodegradable, and exhibited shape memory behavior due to PCL crystallinity within a crosslinked hybrid network, enabling temperature-triggered shape switching to conform to irregular bone defects. In vivo, the hybrid scaffolds promoted osteogenic differentiation and angiogenesis, accelerating bone regeneration (supported by histology, µCT mineralization, and immunostaining for angiogenic/osteogenic markers).

Covalently integrating APTES-functionalized PU with a silica network addressed key limitations of conventional composites by preventing phase separation and strengthening interfacial bonding. Allophanate-mediated branching and increased silane content accelerated crosslinking during sol–gel processing, markedly shortening gelation times from days/weeks (literature) to minutes, thereby facilitating fabrication of 3D porous scaffolds via salt-leaching. FTIR and TGA confirmed hybrid formation and accurate inorganic content; enhanced thermal stability and modulated crystallinity reflect the hybrid network’s influence on polymer phase behavior. The 30 wt.% silica scaffold provided a favorable balance of mechanical robustness and thermal resistance, while the hybrid system preserved flexibility and biodegradability. Shape memory behavior, arising from the semicrystalline PCL phase within a crosslinked matrix, allowed scaffolds to adapt to irregular defects, potentially improving defect filling and interfacial contact. In vivo assessments indicated that these hybrids not only support structural requirements but also actively promote angiogenesis and osteogenesis, key processes in bone remodeling, thereby substantiating the approach for bone repair applications.

This work introduces a tough, fully biodegradable PU–silica hybrid system with organoalkoxysilane-functionalized PU enabling rapid sol–gel gelation within minutes. The hybrids form covalently bonded networks that enhance thermal stability, allow facile fabrication of 3D porous scaffolds, and exhibit shape memory behavior advantageous for fitting irregular bone defects. A 30 wt.% silica scaffold emerged as particularly promising, with favorable mechanical/thermal properties and in vivo promotion of osteogenesis and angiogenesis for accelerated bone regeneration. Future studies could optimize silica content and processing for mechanical performance, explore scalable manufacturing (e.g., 3D printing), and evaluate long-term in vivo degradation, remodeling kinetics, and functional load-bearing performance.

Detailed long-term in vivo outcomes, comprehensive mechanical testing across loading regimes, and full affiliation-specific details of all authors are not provided in the excerpt. Porous scaffolds exhibited reduced crystallinity at higher silica contents, which may influence mechanical properties; the implications and optimization strategies are not fully discussed here. Publication does not provide explicit limitations within the provided text.