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While extensive research has demonstrated an interdependent role of osteogenesis and angiogenesis in bone tissue engineering, little is known about how functional blood vessel networks are organized to initiate and facilitate bone tissue regeneration. Building upon the success of a biomimetic composite nanofibrous construct capable of supporting donor progenitor cell-dependent regeneration, we examined the angiogenic response and spatiotemporal blood vessel specification at the osteogenesis and angiogenesis interface of cranial bone defect repair utilizing high resolution multiphoton laser scanning microscopy (MPLSM) in conjunction with intravital imaging. We demonstrate here that the regenerative vasculature can be specified as arterial and venous capillary vessels based upon endothelial surface markers of CD31 and Endomucin (EMCN), with CD31+EMCN− vessels exhibiting higher flowrate and higher oxygen tension (pO 2) than CD31+EMCN+ vessels. The donor osteoblast clusters are uniquely coupled to the sprouting CD31+EMCN+ vessels connecting to CD31+EMCN− vessels. Further analyses reveal differential vascular response and vessel type distribution in healing and non-healing defects, associated with changes of gene sets that control sprouting and morphogenesis of blood vessels. Collectively, our study highlights the key role of spatiotemporal vessel type distribution in bone tissue engineering, offering new insights for devising more effective vascularization strategies for bone tissue engineering. [Display omitted] [ABSTRACT FROM AUTHOR]

Induction of some specific cell signaling molecules in peptide scaffold play a critical role in developing of functional substitutes for damaged tissue. In this study, a new peptide ELK8 (Ac-LELELKLK-CONH2) was designed by replacing Ala in EAK16 (Ac-AEAEAKAKAEAEAKAK-CONH2) with more hydrophobic residue Leu in order to enhance the strength of peptide. The functionalized peptides were obtained through directly coupling three functional motifs to C-terminal of ELK8, such as osteogenic growth peptide, osteopontin cell adhesion motif, and 2-unit RGD binding sequence. Then, the new self-assembling peptide scaffolds were fabricated by mixing three functionalized peptides severally with pure ELK8 at the ratio of 1:1 (v:v) and the nanostructures of self-assembling peptides were investigated with AFM and DLS. The osteogenic efficacy of designed peptides on mouse pre-osteoblast MC3T3-E1 were examined after cells were incubated in scaffolds for 14 d. The results showed that these functionalized peptides, ALK mix particularly, promoted the attachment, proliferation, and osteogenic differentiation of MC3T3-E1 cells by increasing in cell numbers, ALP activities and osteocalcin concentrations. [ABSTRACT FROM AUTHOR]