Spatiotemporal Immunomodulation and Biphasic Osteo-Vascular Aligned Electrospun Membrane for Diabetic Periosteum Regeneration.

Under diabetic conditions, blood glucose fluctuations and exacerbated immunopathological inflammatory environments pose significant challenges to periosteal regenerative repair strategies. Responsive immune regulation in damaged tissues is critical for the immune microenvironment, osteogenesis, and angiogenesis stabilization. Considering the high-glucose microenvironment of such acute injury sites, a functional glucose-responsive immunomodulation-assisted periosteal regeneration composite material-PLA（Polylactic Acid）/COLI(Collagen I）/Lipo(Liposome）-APY29 (PCLA)-is constructed. Aside from stimulating osteogenic differentiation, owing to the presence of surface self-assembled type I collagen in the scaffolds, PCLA can directly respond to focal area high-glucose microenvironments. The PCLA scaffolds trigger the release of APY29-loaded liposomes, shifting the macrophages toward the M2 phenotype, inhibiting the release of inflammatory cytokines, improving the bone immune microenvironment, and promoting osteogenic differentiation and angiogenesis. Bioinformatics analyses show that PCLA enhances bone repair by inhibiting the inflammatory signal pathway regulating the polarization direction and promoting osteogenic and angiogenic gene expression. In the calvarial periosteal defect model of diabetic rats, PCLA scaffolds induce M2 macrophage polarization and improve the inflammatory microenvironment, significantly accelerating periosteal repair. Overall, the PCLA scaffold material regulates immunity in fluctuating high-glucose inflammatory microenvironments, achieves relatively stable and favorable osteogenic microenvironments, and facilitates the effective design of functionalized biomaterials for bone regeneration therapy in patients with diabetes.

Clinical and serological characterization of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is an uncommon complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) which has only been reported in a few cases. We here aimed to explore its mechanism. METHODS: We retrospectively analyzed 296 patients who underwent allo-HSCT in our center from July 2010 to July 2012. Clinical manifestations were carefully reviewed and the response to currently available treatment approaches were evaluated. The survival and risk factors of AIHA patients after allo-HSCT were further analyzed. RESULTS: Twelve patients were diagnosed with AIHA at a median time of 100 days (15-720 days) after allo-HSCT. The incidence of AIHA after allo-HSCT was 4.1%. IgG antibody were detected in ten patients and IgM antibody in two patients. The two cold antibody AIHA patients had a better response to steroid corticoid only treatment and the ten warm antibody AIHA patients responded to corticosteroid treatment and adjustment of immunosuppressant therapy. Rituximab was shown to be effective for AIHA patients who failed conventional therapy. Survival analysis showed that the combination of AIHA in allo-HSCT patients hinted at poor survival. Cytomegalovirus (CMV) infection, graft-versus-host disease (GVHD) and histocompatibility leukocyte antigen (HLA) mismatch seemed to increase the risk of developing AIHA. CONCLUSIONS: Patients who develop AIHA after allo-HSCT have poor survival compared to non-AIHA patients. Possible risk factors of AIHA are CMV infection, GVHD, and HLA mismatch. Rituximab is likely to be the effective treatment choice for the refractory patients.