Alendronate loaded graphene oxide functionalized collagen sponge for the dual effects of osteogenesis and anti-osteoclastogenesis in osteoporotic rats

Graphene Oxide(GO)-related hydrogels have been extensively studied in hard tissue repair,because GO can not only enhance the mechanical properties of polymers but also promote osteogenic differentiation of mesenchymal stem cells.However,simple GO-related hydrogels are not ideal for the repair of osteoporotic bone defects as the overactive osteoclasts in osteoporosis.Alendronate(Aln)is known to inhibit osteoclasts and may bind to GO through covalent connection.Therefore,delivering Aln in GO-related hydrogels may be effective to repair osteoporotic bone defects.Here,we developed a control-released system which is constructed by collagen(Col)-GO sponges loaded with Aln(Col-GO-Aln)for osteoporotic bone defect repair.In vitro,Col-GO-Aln sponges prolonged the release period of Aln,and the sponge containing 0.05%(w/v)GO released Aln faster than sponge with 0.2%GO.Furthermore,tartrate-resistant acid phosphatase(TRAP)and F-actin staining demonstrated that Col-GO-Aln sponges effectively inhibited osteoclastogenesis of monocyte-macrophages.In vivo,micro-CT scan showed that the volume of newborn bone in defect site by 0.05%GO sponge was nearly three times larger than that of other groups.Moreover,the CT and histological examinations of rat femur proved that Col-GO-Aln sponges decreased the number of osteoclasts and suppressed the systemic bone loss in osteoporotic rats.These findings reveal that the application of GO as carriers of anti-osteoporosis drugs is a viable treatment for osteoporosis.The results also underscore the potential of GO-related hydrogels with Aln-releasing capacity for bone regeneration in osteoporosis.

Simple application of adipose-derived stem cell-derived extracellular vesicles coating enhances cytocompatibility and osteoinductivity of titanium implant

Surface modification using bioactive molecules is frequently performed to improve the biological properties of medical metal biomaterial titanium(Ti)implants.Developmental evidence suggests that mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)served as potent bioactive component.As a subset of MSC EV,adipose-derived stem cel-derived extracellular vesicles(ADSC-EVs)could be obtained from abundant adipose tissue.Meanwhile,it possesses multiple re-generative properties and might be used to endow biological activities to medical Ti implant.Here,we present a simple ADSC-EV coating strategy based on physisorption of fibronectin.This ADSC-EV functionalized Ti implants(EV-Ti)revealed enhanced osteoblast compatibility and osteoinduc-tive activity.Cell spreading area of EV-Ti group was 1.62-and 1.48-fold larger than that of Ti group after 6 and 12 h of cell seeding,respectively.Moreover,EV-Ti promoted alkaline phosphatase,col-lagen 1 and osteocalcin gene expression in osteoblast by 1.51-,1.68-and 1.82-fold compared with pristine Ti,respectively.Thus,the MSC-EVs modification method reported here provide a clinically translatable strategy to promote the bioactivity of Ti implants.