Gelatin methacrylate hydrogel scaffold carrying resveratrol-loaded solid lipid nanoparticles for enhancement of osteogenic differentiation of BMSCs and effective bone regeneration

Critical-sized bone defects caused by traumatic fractures,tumour resection and congenital malformation are unlikely to heal spontaneously.Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts.In this study,we developed an innovative bone engineering scaffold based on gelatin methacrylate(GelMA)hydrogel,obtained via a two-step procedure:first,solid lipid nanoparticles(SLNs)were loaded with resveratrol(Res),a drug that can promote osteogenic differentiation and bone formation;these particles were then encapsulated at different concentrations(0.01%,0.02%,0.04%and 0.08%)in GelMA to obtain the final Res-SLNs/GelMA scaffolds.The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and bone regeneration in rat cranial defects were evaluated using various characterization assays.Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs,with the ideally slow and steady release of Res;the optimal scaffold was 0.02 Res-SLNs/GelMA.Therefore,the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility,osteoconduction and osteoinduction,thereby showing potential for application in bone tissue engineering.

Selenium nanoparticles derived from Proteus mirabilis YC801 alleviate oxidative stress and inflammatory response to promote nerve repair in rats with spinal cord injury

Microbial biotransformation and detoxification of biotoxic selenite into selenium nanoparticles(SeNPs)has emerged as an efficient technique for the utilization of selenium.SeNPs are characterized by high bioavailability and have several therapeutic effects owing to their antioxidant,anti-inflammatory and neuroprotective activities.However,their influence onmicroenvironment disturbances and neuroprotection after spinal cord injury(SCI)is yet to be elucidated.This study aimed to assess the influence of SeNPs on SCI and explore the underlying protective mechanisms.Overall,the proliferation and differentiation of neural stem cells were facilitated by SeNPs derived from Proteus mirabilis YC801 via the Wnt/b-catenin signaling pathway.The SeNPs increased the number of neurons to a greater extent than astrocytes after differentiation and improved nerve regeneration.A therapeutic dose of SeNPs remarkably protected the integrity of the spinal cord to improve the motor function of the hind limbs after SCI and decreased the expression of several inflammatory factors such as tumor necrosis factor-a and interleukin-6 in vivo and enhanced the production of M2-type macrophages by regulating their polarization,indicating the suppressed inflammatory response.Besides,SeNPs reversed the SCI-mediated production of reactive oxygen species.In conclusion,SeNPs treatment holds the potential to improve the disturbed microenvironment and promote nerve regeneration,representing a promising therapeutic approach for SCI.