Strategies for bone tissue regeneration have been continuously evolving for the last 25 years since the introduction of the “tissue engineering” concept. The convergence of the life, physical, and engineering sciences has brought in several advanced technologies available to tissue engineers and scientists. This resulted in the creation of a new multidisciplinary field termed as “regenerative engineering”. In this article, the role of biomaterials in bone regenerative engineering is systematically reviewed to elucidate the new design criteria for the next generation of biomaterials for bone regenerative engineering. We highlight the exemplary design of biomaterials harnessing various materials characteristics towards successful bone defect repair and regeneration. In particular, we concentrate our attention on the attempts of incorporating advanced materials science, stem cell technologies, and developmental biology into biomaterials design to engineer and develop the next generation bone grafts.

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Enzymatically cross-linkable phenol-conjugated glycol chitosan was prepared by reacting glycol chitosan with 3-(4-hydroxyphenyl)propionic acid (HPP). The chemical modification was confirmed by FTIR, 1 H-NMR and UV spectroscopy. Glycol chitosan hydrogels (HPP-GC) with or without rhBMP-2 were prepared by the oxidative coupling of the substituted phenol groups in the presence of hydrogen peroxide and horse radish peroxidase. Rheological characterization demonstrated the feasibility of developing hydrogels with varying storage moduli by changing the polymer concentration. The gel presented a microporous structure with pore sizes ranging from 50-350 mm. The good viability of encapsulated 7F2 osteoblasts indicated non-toxicity of the gelation conditions. In vitro release of rhBMP-2 in phosphate buffer solution showed B11% release in 360 h. The ability of the hydrogel to maintain the in vivo bioactivity of rhBMP-2 was evaluated in a bilateral critical size calvarial bone defect model in Col3.6 transgenic fluorescent reporter mice. The presence of fluorescent green osteoblast cells with overlying red alizarin complexone and yellow stain indicating osteoclast TRAP activity confirmed active cell-mediated mineralization and remodelling process at the implantation site. The complete closure of the defect site at 4 and 8 weeks post implantation demonstrated the potent osteoinductivity of the rhBMP-2 containing gel.

The aim of the study is use of transgenic fluorescent protein reporter mouse models to understand the cellular processes in recombinant human bone morphogenetic protein-2 (rhBMP-2) mediated bone formation. Bilateral parietal calvarial bone defects in Col3.6Topaz transgenic fluorescent osteoblast reporter mouse were used to understand the bone formation in the presence and absence of rhBMP2 and/or Col3.6Cyan bone marrow derived stromal cells (BMSCs), using collagen-hydroxyapatite matrix (Healos) as a biomaterial. The bone regeneration was not confined to the site of BMP-2 implantation and significant bone formation was observed in the neighboring defect site. Osteogenic cellular activity with overlying alizarin complexone staining was observed in both the defects indicating host cell induced mineralization. However, implantation of BMSCs along with rhBMP-2 demonstrated a donor cell derived bone formation. The presence of rhBMP-2 did not support host cell recruitment in the presence of donor cells. This study demonstrates the potential of multiple fluorescent reporters to understand the cellular processes involved in the bone regeneration process using biomaterials, growth factors, and/or stem cells.

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Acute or chronic pain associated with musculoskeletal conditions is considered a major health issue, with healthcare costs totaling several billion dollars. The opioid crisis presents a pressing clinical need to develop alternative and effective approaches to treat musculoskeletal pain. The goal of this study was to develop a long-acting injectable anesthetic formulation which can sustain a local anesthetic effect for a prolonged time. This in turn could increase the quality of life and rehabilitation outcome of patients, and decrease opioid consumption. The developed injectable nanocomposite demonstrated the feasibility to achieve prolonged pain relief in a rat chronic constriction injury (CCI) model.

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