Abstract
Non-availability of an ideal alternative for autografts in treating critical-size bone defects is a major challenge in orthopedics. Phytocompounds have been proven to enhance osteogenesis via various osteogenic signaling pathways, but its decreased bioavailability and increased renal clearance limit its application. In this study, we designed a biocomposite scaffold comprising gelatin (Gel) and nanohydroxyapatite (nHAp) incorporated with diosmin (DM) and we investigated its bone forming potential in vitro and in vivo. Physiochemical characterization of the scaffold showed that DM had no effect on altering the material characteristics of the scaffold. The addition of DM enhanced the osteoblast differentiation potential of the scaffold in mouse mesenchymal stem cells at both cellular and molecular levels, possibly via the integrin-mediated activation of FAK and ERK signaling components. Using the rat tibial bone defective model, we identified the effect of DM in Gel/nHAp scaffold on enhancing bone formation in vivo. Based on our results, we suggest that Gel/nHAp/DM can be a potential therapeutic agent in scaffold-mediated bone regeneration.
Highlights
Bone and cartilage ailments, such as osteoporosis, arthritis, and spinal injuries, etc., not life threatening, diminish the quality of life with continuous pain, discomfort and restricted locomotion[1]
The obtained scaffold was subjected to physicochemical and material characterization using Scanning electron microscope (SEM), Fouriertransform infrared spectroscopy (FTIR), X-ray diffraction (XRD), swelling, protein adsorption, degradation, and biomineralization studies according to previously described protocols[31,32]
Growth factor (GF)-incorporated biomaterials are considered a plausible alternative to autografts for bone regeneration
Summary
Bone and cartilage ailments, such as osteoporosis, arthritis, and spinal injuries, etc., not life threatening, diminish the quality of life with continuous pain, discomfort and restricted locomotion[1]. Phytocompounds are known to have several medicinal properties and incorporation of phytocompounds into scaffold matrices is advantageous for enhanced bone regeneration[5,6,7] It can be considered a possible alternative for growth factor (GF)-mediated therapy. The major drawback of scaffold-mediated regenerative therapies is the failure in mimicking the extracellular matrix (ECM) environment for cell adhesion Surface modification strategies, such as coating the scaffold surface with several integrin-specific ligands, like RGD, GFOGER, are currently being investigated for enhanced cell adhesion[8,9]. These techniques were highly successful in cell culture models, but failed to reproduce the same results in vivo[8]. Several studies showed that combining such water-insoluble compounds with natural hydrophilic polymers might alter the nature of the compound providing sustained and prolonged delivery of compounds and better absorption to the target site[23,24,25,26]
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