To develop a customized hydrogel scaffold that unifies toughness and calcium–phosphorus (Ca-P) ion reservoir through compression training for the tooth extraction socket, and to evaluate its efficacy for alveolar bone regeneration under a diabetes-delayed healing condition. Polyvinyl alcohol (PVA) and nano-hydroxyapatite (nHA) mixed solution was processed by directional freezing to create aligned architectures and by sodium-citrate salting-out to consolidate physical networks. The formed hydrogels then underwent compression training at 30% strain for 400 cycles. Mechanical properties were measured under monotonic and cyclic compression. Ca and P ion release during compression training was quantified. In vitro osteogenesis was assessed using alkaline phosphatase (ALP) staining and Alizarin Red S staining. In vivo efficacy was tested with a diabetic rat extraction-socket model by micro-CT, histology, and immunohistochemistry. Compression training densified aligned polymeric bundles and redistributed minerals from aggregates to a more uniform exposure along porous walls. Trained nHA/PVA showed an upward shift of the stress–strain curves with increased toughness, and exhibited reproducible loops and improved fatigue stability in cyclic compression tests. Ca and P in eluates increased with training cycles, consistent with a compression-triggered ion reservoir. The trained nHA/PVA group showed higher ALP activity and Alizarin Red staining. In the rat model, the nHA/PVA hydrogel produced more complete defect fill, higher radiodensity, and improved trabecular number and spacing. The immunohistology shows stronger BMP-2 and type I collagen staining for the nHA/PVA hydrogel compared with controls. An all-physical processing route yields tough nHA/PVA hydrogels with increased Ca and P release, enhancing osteogenesis in vitro and accelerating bone regeneration in a rat model. The nHA/PVA hydrogel fabricated by simple physical steps offers easy handling, stable support, and compression-triggered Ca-P release, providing a clinically practical option for socket preservation, particularly in delayed healing conditions such as diabetes. ● A purely physical process yields customized and tough nHA/PVA hydrogels. ● The hydrogel acts as a compression-responsive Ca-P reservoir, enhancing healing in a diabetic rat extraction-socket model. ● Simple composition and no-added-chemistry preparation method facilitate clinical translation.
Tang et al. (Thu,) studied this question.