Lysozyme Self-Assembled PTLA Hydrogel Promotes Diabetic Socket Bone Healing

This study aimed to develop an injectable PTLA hydrogel using a temperature-dependent protein aggregation (TPA) strategy to encapsulate alogliptin, addressing the clinical challenges of impaired healing, persistent inflammation, and high infection risk in tooth extraction sockets of diabetic patients. The self-assembled PTLA hydrogel was prepared from lysozyme and tris(2-carboxyethyl)phosphine (TCEP), with alogliptin incorporated for drug delivery. Structural characterization was performed using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and circular dichroism (CD) spectroscopy. The mechanical properties of the hydrogel were evaluated through rheological tests. The drug release kinetics were monitored by UV spectrophotometry. In vitro assessments included the CCK-8 assay, live/dead staining, alkaline phosphatase (ALP) activity, and alizarin red staining. A diabetic rat model was established to evaluate bone regeneration through micro-CT, hematoxylin and eosin (H&E) staining, aniline blue staining, and tartrate-resistant acid phosphatase (TRAP) staining. The PTLA hydrogel exhibited a porous network structure with suitable mechanical strength and injectability. In vitro studies demonstrated excellent biocompatibility, significant anti-inflammatory effects under high-glucose conditions, and enhanced osteogenic differentiation. In vivo results confirmed accelerated bone healing in diabetic extraction sockets. The PTLA hydrogel effectively promotes bone regeneration in diabetic tooth extraction sockets through dual osteogenic and anti-inflammatory mechanisms, offering a promising therapeutic approach for diabetic oral wound healing.