Three-dimensional (3D) gelatin sponge (GS) scaffolds were constructed by ensheathing GS with a thin film of poly-(lactide-co-glycolide) (PLGA). Rat bone marrow-derived mesenchymal stem cells (MSCs) were isolated, cultured, and then seeded to the scaffolds. Distribution of cells and cell growth, survival, and proliferation within the scaffolds were then determined. Immunofluorescence and Western blot analysis were employed to detect the deposition of fibronectin to the scaffolds on day 3 and day 7 of culture. Scaffolds with or without MSCs were then transplanted into the transected rat spinal cord. One or 8 weeks following transplantation, cavity areas, activated macrophages/microglia, expression of TNF-α and IL-1β, and neovascularization within the grafts were examined and quantified. Deposition of fibronectin (FN) and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) as potential inducing factors for angiogenesis were also examined. Results showed that 3D GS scaffolds allowed MSCs to adhere, survive, and proliferate and also FN to deposit. In vivo transplantation experiments demonstrated that these scaffolds were biocompatible, and MSCs seeded to the scaffolds played an important role in attenuating inflammation, promoting angiogenesis, and reducing cavity formation. Therefore, the GS scaffolds with MSCs may serve as promising supporting transplants for repairing spinal cord injury.
Semiconductor-metal-organic framework (MOF) hybrid photocatalysts have attracted increasing attention because of their enhanced photocatalytic activity. However, the effect of the interface reaction between semiconductor and MOFs is rarely studied. In this work, we studied the synthesis and photocatalytic activity of zeolitic imidazolate framework-8 (ZIF-8) decorated electrostatic spinning TiO2 nanofibers (TiO2 ESNFs). TiO2/ZIF-8 hybrid photocatalysts were prepared via a facile sonochemical route. It was crucial that the ZIF-8 was assembled homogeneously on the surface of TiO2 ESNFs and formed a N-Ti-O bond under sonochemical treatment, which may result in reducing recombination of the electron-hole pairs. The chemically bonded TiO2/ZIF-8 nanocomposites displayed excellent performance of thermal stability, controllable crystallinity, and great enhancement of photocatalytic activity in Rhodamine B (Rh B) photodegradation. Furthermore, the UV-vis light adsorption spectra of TiO2/ZIF-8 nanocomposites showed that the ZIF-8 photosensitizer extended the spectral response of TiO2 to the visible region. The new strategy reported here can enrich the method for designing new semiconductor-MOF hybrid photocatalysts.
Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9-T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI.spinal cord injury | recovery neurobiology | mesenchymal stromal stem cell | PLGA | locomotion R epair of neurotrauma, stroke, and neurodegenerative diseases remains an unmet medical demand because of their pathophysiological complexity and the limited spontaneous healing capacity of adult mammalian CNS. Human mesenchymal stromal stem cells (hMSCs) offer autologous transplantation feasibility (1-4) and have been studied both experimentally and clinically for traumatic brain injury (TBI) and spinal cord injury (SCI) (5-8). Although MSCs possess homeostatic and proneurogenic activities (7, 9), studies relying on neural transdifferentiation (i.e., putative differentiations of MSCs into neural cells without reentering the pluripotency phase) did not show long-term functional improvement in SCI models. The poor outcomes were attributed mainly to suboptimal survival of MSCs, leaving key therapeutic mechanisms undetermined (10). We previously established a 3D cell delivery technology by seeding neural stem cells (NSCs) in biodegradable polymer scaffolds that significantly improved donor efficacy and enabled investigation of NSC repair mechanisms in t...
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