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Traditional methods of bone defect repair include autografts, allografts, surgical reconstruction, and metal implants that have several disadvantages such as donor site morbidity, rejection, risk of disease transmission, and repetitive surgery. Biomaterial‐based bone reconstructions can, therefore, be an efficient alternative due to the inherent properties of the materials. Chitosan (CS), the deacetylated form of chitin, is a biopolymer having a wide array of applicability in regenerative tissue applications owing to its biocompatible, in vitro degradative and bioresorbable nature. Extensive studies are being carried out using CS to augment the properties of the already existing methods and to also improve the applicability of CS‐based biocomposites in bone tissue repair. In this review, the suitability of CS as a surface modifier has been discussed in detail for the already existing implants, surface modifications of CS‐based natural biocomposites for bone tissue regeneration, and the wide range of techniques that can introduce these modifications. CS, being a natural polymer, possesses advantageous properties including surface modifier that makes it a suitable candidate for bone regeneration, and further research to investigate its osteogenic potential in vivo along with the molecular and signaling mechanisms involved in bone regeneration can aid in expanding its applicability in clinical trials.

Background: Recent reports have unveiled the potential of flavonoids to enhance bone formation and assuage bone resorption due to their involvement in cell signaling pathways. They also act as an effective alternative to circumvent the disadvantages associated with existing treatment methods, which has increased their scope in orthopedic research. Valproic acid (VA, 2-propylpentanoic acid) is one such flavonoid, obtained from an herbaceous plant, used in the treatment of epilepsy and various types of seizures. Objective: In this study, the role of VA in osteogenesis and the molecular mechanisms underpinning its action in mouse mesenchymal stem cells (mMSCs) were determined. Methods & Results: Cytotoxic studies validated VA’s amiable nature in mMSCs. Alizarin red and von Kossa staining results showed an increased deposition of calcium phosphate in VA-treated mMSCs, which confirmed the occurrence of osteoblast differentiation and mineralization at a cellular level. At the molecular level, there were increased levels of expression of Runx2, a vital bone transcription factor, and other major osteoblast differentiation marker genes in the VAtreated mMSCs. Further, VA-treatment in mMSCs upregulated mir-21 and activated the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway, which might be essential for the expression/activity of Runx2. Conclusion: Thus, the current study confirmed the osteoinductive nature of VA at the cellular and molecular levels, opening the possibility for its application in bone therapeutics with mir-21.

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