Bone physiology as inspiration for tissue regenerative therapies

Abstract

The development, maintenance of healthy bone and regeneration of injured tissue in the human body comprise a set of intricate and finely coordinated processes. However, an analysis of current bone regeneration strategies shows that only a small fraction of well-reported bone biology aspects has been used as inspiration and transposed into the development of therapeutic products. Specific topics that include inter-scale bone structural organization, developmental aspects of bone morphogenesis, bone repair mechanisms, role of specific cells and heterotypic cell contact in the bone niche (including vascularization networks and immune system cells), cell-cell direct and soluble-mediated contact, extracellular matrix composition (with particular focus on the non-soluble fraction of proteins), as well as mechanical aspects of native bone will be the main reviewed topics. In this Review we suggest a systematic parallelization of (i) fundamental well-established biology of bone, (ii) updated and recent advances on the understanding of biological phenomena occurring in native and injured tissue, and (iii) critical discussion of how those individual aspects have been translated into tissue regeneration strategies using biomaterials and other tissue engineering approaches. We aim at presenting a perspective on unexplored aspects of bone physiology and how they could be translated into innovative regeneration-driven concepts.

Gelatin Nanoparticle‐Injectable Platelet‐Rich Fibrin Double Network Hydrogels with Local Adaptability and Bioactivity for Enhanced Osteogenesis

“…Biophysical signals on the other hand are influenced by topographical and mechanical properties of ECM and also the mechanical stimuli generating from physiological activities. In case of sinus, the physiological process of respiration and rhythmic movements can influence healing of bony defects . The interplay of these environmental cues along with biochemical factors play a pivotal role in determining bone formation and bone remodeling and presents as an enormous challenge toward bone regeneration.…”

“…The interplay of these environmental cues along with biochemical factors play a pivotal role in determining bone formation and bone remodeling and presents as an enormous challenge toward bone regeneration. Enormous efforts have been made to replicate these intricate physiologically process for the purpose of bone tissue regeneration …”

“…From the biophysical aspect, scaffolds that mechanically mimics the natural ECM of bones and adapts to the irregular shape and local mechanical stimuli at the defect site is of tremendous significance for the regeneration of bone tissue . A large number of previous studies have pointed out osteogenesis can be substantially affected by mechanical stimuli such as rhythmic compression or extension . Particularly, stem cells have been demonstrated to be mechano‐responsive, in which mechanical features such as stiffness, stress relaxation, and creep can significantly steer stem cell fate .…”

Therapeutic vascularization in regenerative medicine

“…In particular, bone replacement is required in several situations due to trauma, surgery, or idiopathic conditions such as avascular necrosis of small bones, where spontaneous regeneration is insufficient. Bone tissue‐engineering holds promise for the generation of osteogenic grafts, combining osteo‐progenitors with biocompatible scaffolds . However, for defects of clinically relevant size, the lack of rapid vascularization in vivo causes severe ischemia and progenitor death in the graft core deeper than 1 to 2 mm .…”

“…Bone tissue-engineering holds promise for the generation of osteogenic grafts, combining osteo-progenitors with biocompatible scaffolds. 5,6 However, for defects of clinically relevant size, the lack of rapid vascularization in vivo causes severe ischemia and progenitor death in the graft core deeper than 1 to 2 mm. 7 Similar biological principles apply to the vascularization of both ischemic tissue and engineered grafts, but with different translational considerations.…”