Bone-tissue defects affect millions of people worldwide. Despite being common treatment approaches, autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect. This has prompted researchers to explore novel bone-regeneration methods. In recent decades, the development of bone tissue engineering (BTE) scaffolds has been leading the forefront of this field. As researchers have provided deep insights into bone physiology and the bone-healing mechanism, various biomimicking and bioinspired BTE scaffolds have been reported. Now it is necessary to review the progress of natural bone physiology and bone healing mechanism, which will provide more valuable enlightenments for researchers in this field. This work details the physiological microenvironment of the natural bone tissue, bone-healing process, and various biomolecules involved therein. Next, according to the bone physiological microenvironment and the delivery of bioactive factors based on the bone-healing mechanism, it elaborates the biomimetic design of a scaffold, highlighting the designing of BTE scaffolds according to bone biology and providing the rationale for designing next-generation BTE scaffolds that conform to natural bone healing and regeneration.

Cell polarization exists in a variety of tissues to regulate cell behaviors and functions. Space constraint (spatially limiting cell extension) and adhesion induction (guiding adhesome growth) are two main ways to induce cell polarization according to the microenvironment topographies. However, the mechanism of cell polarization induced by these two ways and the downstream effects on cell functions are yet to be understood. Here, space constraint and adhesion induction guiding cell polarization are achieved by substrate groove arrays in micro and nano size, respectively. Although the morphology of polarized cells is similar on both structures, the signaling pathways to induce the cell polarization and the downstream functions are distinctly different. The adhesion induction (nano‐groove) leads to the formation of focal adhesions and activates the RhoA/ROCK pathway to enhance the myosin‐based intracellular force, while the space constraint (micro‐groove) only activates the formation of pseudopodia. The enhanced intracellular force caused by adhesion induction inhibits the chromatin condensation, which promotes the osteogenic differentiation of stem cells. This study presents an overview of cell polarization and mechanosensing at biointerface to aid in the design of novel biomaterials.

No abstract

Considering the critical impacts of protein adsorption on NPs delivery, our work could be an urgent warning about the possible risks of dosage adjustment of nanoformulations.

Bone defects caused heavy social and economic burdens worldwide. Nel‐like molecule, type 1 (NELL‐1) could enhance the osteogenesis and the repairment of bone defects, while the specific mechanism remains to be elucidated. Circular RNAs (circRNAs) have been found to play critical roles in the tissue development and serve as biomarkers for various diseases. However, it remains unclear that the expression patterns of circRNAs and the roles of them played in recombinant NELL‐1‐induced osteogenesis of human adipose‐derived stem cells (hASCs). In this study, we performed RNA‐sequencing to investigate the expression profiles of circRNAs in recombinant NELL‐1‐induced osteogenic differentiation and identified two key circRNAs, namely circRFWD2 and circINO80. These two circRNAs were confirmed to be up‐regulated during recombinant NELL‐1‐induced osteogenesis, and knockdown of them affected the positive effect of NELL‐1 on osteogenesis. CircRFWD2 and circINO80 could interact with hsa‐miR‐6817‐5p, which could inhibit the osteogenesis. Silencing hsa‐miR‐6817‐5p could partially reverse the negative effect of si‐circRFWD2 and si‐circINO80 on the osteogenesis. Therefore, circRFWD2 and circINO80 could regulate the expression of hsa‐miR‐6817‐5p and influence the recombinant NELL‐1‐induced osteogenic differentiation of hASCs. It opens a new window to better understanding the effects of NELL‐1 on the osteogenic differentiation of hASCs and provides potential molecular targets and novel methods for bone regeneration efficiently and safely.