Neuro-Inspired Biomimetic Microreactor for Sensory Recovery and Hair Follicle Neogenesis under Skin Burns.

Deep burns are one of the most severe skin wounds, with typical symptoms being a contradiction between initial severe pain and a subsequent loss of sensation. Although it has long been known that sensory nerves promote skin regeneration and modulate skin function, no proven burn management strategies target sensory nerves. Here, a neuro-inspired biomimetic microreactor is designed based on the immune escape outer membrane of neuroblastoma cells and neural-associated intracellular proteins. The microreactor is constructed on a metal-organic framework (MOF) with a neuroblastoma membrane coating the surface and intracellular proteins loaded inside, called Neuro-MOF. It is loaded into a therapeutic hydrogel and triggers the release of its content proteins upon excitation by near-infrared light. The proteins compensate the skin microenvironment for permanent neurological damage after burns to initiate peripheral nerve regeneration and hair follicle niche formation. In addition, the neuroblastoma cell membrane is displayed on the surface of the Neuro-MOF microreactor, decreasing its immunogenicity and suppressing local inflammation. In a mouse model of deep skin burns, the Neuro-MOF microreactor exhibited significant functional skin regeneration effects, particularly sensory recovery and hair follicle neogenesis.

Mitochondrial Transfer Regulates Cell Fate Through Metabolic Remodeling in Osteoporosis.

Mitochondria are the powerhouse of eukaryotic cells, which regulate cell metabolism and differentiation. Recently, mitochondrial transfer between cells has been shown to direct recipient cell fate. However, it is unclear whether mitochondria can translocate to stem cells and whether this transfer alters stem cell fate. Here, mesenchymal stem cell (MSC) regulation is examined by macrophages in the bone marrow environment. It is found that macrophages promote osteogenic differentiation of MSCs by delivering mitochondria to MSCs. However, under osteoporotic conditions, macrophages with altered phenotypes, and metabolic statuses release oxidatively damaged mitochondria. Increased mitochondrial transfer of M1-like macrophages to MSCs triggers a reactive oxygen species burst, which leads to metabolic remodeling. It is showed that abnormal metabolism in MSCs is caused by the abnormal succinate accumulation, which is a key factor in abnormal osteogenic differentiation. These results reveal that mitochondrial transfer from macrophages to MSCs allows metabolic crosstalk to regulate bone homeostasis. This mechanism identifies a potential target for the treatment of osteoporosis.

CD301b+ macrophages mediate angiogenesis of calcium phosphate bioceramics by CaN/NFATc1/VEGF axis.

Calcium phosphate (CaP) bioceramics are important for tissue regeneration and immune response, yet how CaP bioceramics influence these biological processes remains unclear. Recently, the role of immune cells in biomaterial-mediated regeneration, especially macrophages, has been well concerned. CD301b+ macrophages were a new subset of macrophages we have discovered, which were required for bioceramics-mediated bone regeneration. Nevertheless, the impact of CD301b+ macrophages on angiogenesis, which is a vital prerequisite to bone formation is yet indistinct. Herein, we found that CD301b+ macrophages were closely correlated to angiogenesis of CaP bioceramics. Additionally, depletion of CD301b+ macrophages led to the failure of angiogenesis. We showed that store-operated Ca2+ entry and calcineurin signals regulated the VEGF expression of CD301b+ macrophages via the NFATc1/VEGF axis. Inhibition of calcineurin effectively impaired angiogenesis via decreasing the infiltration of CD301b+ macrophages. These findings provided a potential immunomodulatory strategy to optimize the integration of angiogenesis and bone tissue engineering scaffold materials.