Natural bone is a highly vascularized tissue that relies on the vasculature for blood and nutrients supply to maintain skeletal integrity. Inadequacy of neovascularization may compromise the tissue ingrowth to the implanted scaffolds, and eventually results in failure for the repair. To tackle this issue and enhance self-vascularized bone regeneration, herein a 3D biomimetic selective lasersintering (SLS) derived scaffold, with an angiogenic growth factor immobilized on its surface, that can be released in a controlled manner is proposed. To this end, a porous polycaprolactone/hydroxyapatite (PCL/HA) scaffold is prepared via the SLS technique, which is further modified with vascular endothelial growth factor (VEGF) by coprecipitation with apatite. The resultant scaffold (PCL/HA/VEGF) has an excellent cytocompatibility, and subcutaneous implantation experiment shows that the VEGF-loaded scaffold significantly enhances the blood vessel formation compared with the VEGF-free control. It is further demonstrated that the PCL/HA/VEGF scaffold is able to enhance the in vivo bone regeneration in a rat cranial defect model. Taken together, the current study provides not only a feasible and promising scaffold candidate to enhance the vascularized bone regeneration, but also a general strategy to overcome the inadequate vascularization issue for the repair of other tissue and organs.

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Cellular bioenergetics (CBE) plays a critical role in tissue regeneration. Physiologically, an enhanced metabolic state facilitates anabolic biosynthesis and mitosis to accelerate regeneration. However, the development of approaches to reprogram CBE, toward the treatment of substantial tissue injuries, has been limited thus far. Here, we show that induced repair in a rabbit model of weight-bearing bone defects is greatly enhanced using a bioenergetic-active material (BAM) scaffold compared to commercialized poly(lactic acid) and calcium phosphate ceramic scaffolds. This material was composed of energy-active units that can be released in a sustained degradation-mediated fashion once implanted. By establishing an intramitochondrial metabolic bypass, the internalized energy-active units significantly elevate mitochondrial membrane potential (ΔΨm) to supply increased bioenergetic levels and accelerate bone formation. The ready-to-use material developed here represents a highly efficient and easy-to-implement therapeutic approach toward tissue regeneration, with promise for bench-to-bedside translation.

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Selenite‐doped bone mineral nanoparticles can retard the growth of osteosarcoma in a nude mice model, through sustained release of selenite ions. The selenite ions released from the nanoparticles through a degradation‐mediated fashion inhibit tumor metastasis. Blood routine analysis indicates that selenite ions can also improve the functions of liver, kidney, and heart.

Summary It was posited that functionalities of GPCRs require full-length sequences that are negated by residue deletions. Here we report that significantly truncated nfCCR5 QTY and nfCXCR4 QTY still bind native ligands. Receptor-ligand interactions were discovered from yeast 2-hybrid screening and confirmed by mating selection. Two nfCCR5 QTY (SZ218a, SZ190b) and two nfCXCR4 QTY (SZ158a, SZ146a) were expressed in E. coli . Synthesized receptors exhibited α-helical structures and bound respective ligands with reduced affinities. SZ190b and SZ158a were reconverted into non-QTY forms and expressed in HEK293T cells. Reconverted receptors localized on cell membranes and functioned as negative regulators for ligand-induced signaling when co-expressed with full-length receptors. CCR5-SZ190b individually can perform signaling at a reduced level with higher ligand concentration. Our findings provide insight into essential structural components for CCR5 and CXCR4 functionality, while raising the possibility that non-full-length receptors may be resulted from alternative splicing and that pseudo-genes in genomes may be present and functional in living organisms.

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