No abstract

Over the past few years, tissue-engineering technology provided a new direction for bone defects therapy, which involved developing applicable biological materials composite with seed cells to repair bone defects tissue....

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) – osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a rat femoral bone defect, the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography (μ-AG) and micro-computational tomography (μ-CT). Based on the immunofluorescence studies, PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors. In addition, superior osseointegration was observed by a direct host bone-PCL interface, which was likely attributed to the formation of type H vessels. The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration. It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels, which could compensate for the inherent biological inertness of synthetic polymers.

Successful wound healing depends on the reconstruction of proper tissue homeostasis, particularly in the posttraumatic inflammatory tissue microenvironment. Diabetes jeopardizes tissues’ immune homeostasis in cutaneous wounds, causing persistent chronic inflammation and cytokine dysfunction. Previously, we developed an autologous regeneration factor (ARF) technology to extract the cytokine composite from autologous tissue to restore immune homeostasis and promote wound healing. However, treatment efficacy was significantly compromised in diabetic conditions. Therefore, we proposed that a combination of melatonin and ARF, which is beneficial for proper immune homeostasis reconstruction, could be an effective treatment for diabetic wounds. Our research showed that the utilization of melatonin-mediated ARF biogel (AM gel) promoted diabetic wound regeneration at a more rapid healing rate. RNA-seq analysis showed that AM gel treatment could restore more favorable immune tissue homeostasis with unique inflammatory patterning as a result of the diminished intensity of acute and chronic inflammation. Currently, AM gel could be a novel and promising therapeutic strategy for diabetic wounds in clinical practice through favorable immune homeostatic reconstructions in the tissue microenvironment and proper posttraumatic inflammation patterning.