Abstract
Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The future of regenerative medicine is the combination of advanced biomaterials, structures, and cues to re-engineer/guide stem cells to yield the desired organ cells and tissues. Tissue engineering strategies were ideally suited to repair damaged tissues; however, the substitution and regeneration of large tissue volumes and multi-level tissues such as complex organ systems integrated into a single phase require more than optimal combinations of biomaterials and biologics. We highlight bioinspired advancements leading to novel regenerative scaffolds especially for musculoskeletal tissue repair and regeneration. Tissue and organ regeneration relies on the spatial and temporal control of biophysical and biochemical cues, including soluble molecules, cell-cell contacts, cell-extracellular matrix contacts, and physical forces. Strategies that recapitulate the complexity of the local microenvironment of the tissue and the stem cell niche play a crucial role in regulating cell self-renewal and differentiation. Biomaterials and scaffolds based on biomimicry of the native tissue will enable convergence of the advances in materials science, the advances in stem cell science, and our understanding of developmental biology.
Highlights
Incidents of tissue loss or organ failure due to accidents, injuries, and disease are debilitating and have led to increased health care costs the world over [1]
Over the past two decades, numerous biomaterials including synthetic and natural polymers, ceramics, and metals have been actively investigated for tissue engineering applications
Lo et al have shown that stimulation of protein kinase A (PKA) signaling pathway by continuous administration of 6-Bnz-cAMP which is a PKA-specific cyclic adenosine monophosphate analog promoted in vitro osteogenesis in MC3T3-E1 and hMSCs [46]
Summary
Incidents of tissue loss or organ failure due to accidents, injuries, and disease are debilitating and have led to increased health care costs the world over [1]. When the polymer scaffold completely degrades, the regenerated bone tissue possesses approximately 70% void volume resembling that of human trabecular bone These 3D porous scaffolds can act as a delivery vehicle for bioactive molecules, growth factors, and cells to the defect site for tissue morphogenesis and defect healing. Microspheres in the diameter range of 300–425, 600–710, and 710–800 μm were fabricated into 3D porous structures via a solvent/nonsolvent sintering technique [35] These microsphere scaffolds fabricated from natural polymers show compressive mechanical properties in the midrange of human trabecular bone and functionalization with collagen nanofibers did not compromise mechanical and pore properties. Proliferation, alkaline phosphatase expression, and mineralized matrix synthesis on these scaffolds were evidenced as compared to that on control tissue culture plastic and PLAGA scaffolds confirming their potential for bone regeneration
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