A robust and biodegradable hydroxyapatite/poly(lactide-co-ε-caprolactone) electrospun membrane for dura repair.

Typically occurring after trauma or neurosurgery treatments, dura mater defect and the ensuing cerebrospinal fluid (CSF) leakage could lead to a number of serious complications and even patient's death. Although numerous natural and synthetic dura mater substitutes have been reported, none of them have been able to fulfill the essential properties, such as anti-adhesion, leakage blockage, and pro-dura rebuilding. In this study, we devised and prepared a series of robust and biodegradable hydroxyapatite/poly(lactide-co-ε-caprolactone) (nHA/PLCL) membranes for dura repair via an electrospinning technique. In particular, PLLA/PCL (80/20) was selected for electrospinning due to its mechanical properties that most closely resembled natural dural tissue. Studies by SEM, XRD, water contact angle and in vitro degradation showed that the introduction of nHA would destroy PLCL's crystalline structure, which would further affect the mechanical properties of the nHA/PLCL membranes. When the amount of nHA added increased, so did the wettability and in vitro degradation rate, which accelerated the release of nHA. In addition, the high biocompatibility of nHA/PLCL membranes was demonstrated by in vitro cytotoxicity data. The in vivo rabbit dura repair model results showed that nHA/PLCL membranes provided a strong physical barrier to stop tissue adhesion at dura defects. Meanwhile, the nHA/PLCL and commercial group's CSF had a significantly lower number of inflammatory cells than the control groups, validating the nHA/PLCL's ability to effectively lower the risk of intracranial infection. Findings from H&E and Masson-trichrome staining verified that the nHA/PLCL electrospun membrane was more favorable for fostering dural defect repair and skull regeneration. Moreover, the relative molecular weight of PLCL declined dramatically after 3 months of implantation, according to the results of the in vivo degradation test, but it retained the fiber network structure and promoted tissue growth, demonstrating the good stability of the nHA/PLCL membranes. Collectively, the nHA/PLCL electrospun membrane presents itself as a viable option for dura repair.

Preparation of an injectable and photocurable carboxymethyl cellulose/hydroxyapatite composite and its application in cranial regeneration.

Limited bone regeneration, uncontrollable degradation rate, mismatched defect zone and poor operability have plagued the reconstruction of irregular bone defect by tissue-engineered materials. A combination of biomimetic scaffolds with hydroxyapatite has gained great popularity in promoting bone regeneration. Therefore, we designed an injectable, photocurable and in-situ curing hydrogel by methacrylic anhydride -modified carboxymethyl cellulose (CMC-MA) loading with spherical hydroxyapatite (HA) to highly simulate the natural bony matrix and match any shape of damaged tissue. The prepared carboxymethyl cellulose-methacrylate/ hydroxyapatite(CMC-MA/HA) composite presented good rheological behavior, swelling ratio and mechanical property under light illumination. Meanwhile, this composite hydrogel promoted effectively proliferation, supported adhesion and upregulated the osteogenic-related genes expression of MC3T3-E1 cells in vitro, as well as the activity of the osteogenic critical protein, Integrin α1, ß1, Myosin 9, Myosin 10, BMP-2 and Smad 1 in Integrin/BMP-2 signal pathway. Together, the composite hydrogels realized promotion of bone regeneration, deformity improvement, and the enhanced new bone strength in skull defect. It also displayed a good histocompatibility and stability of subcutaneous implantation in vivo. Overall, this study laid the groundwork for future research into developing a novel biomaterial and a minimally invasive therapeutic strategies for reconstructing bone defects and contour deficiencies.

BMSCs attenuate radiation-induced brain injury induced hippocampal neuronal apoptosis through a PI3K/Akt/Bax/Bcl-2 signaling pathway.

BACKGROUND: Bone marrow mesenchymal stem cell (BMSCs) -based therapies represent a promising treatment for neurological disorders. However, therapeutic effects and mechanisms of BMSCs transplantation for radiation-induced brain injury (RIBI) have not been fully disclosed. In this article, we explored the functions of BMSCs transplantation on RIBI and investigated the protective effects of BMSCS on hippocampal neurons in RIBI as well as the related molecular mechanisms. MATERIALS AND METHODS: 6-8 weeks-old rats were used to build a RIBI model. Rats in BMSC group were treated with a 3 × 106 BMSCs injection through the tail vein on the 1st day and 8th day after irradiation; rats in both control and RIBI groups were injected with an equivalent volume of physiological saline for comparisons. The Morris water maze was applied to detect the variations in cognitive function after RIBI. MRS was performed to test changes in NAA/Cr, indicating neuronal apoptosis after RIBI. TUNEL was conducted to detect apoptosis of rat hippocampal neurons, and HE staining was carried out to show pathological variations in the hippocampal region of rats. Protein levels of PI3K, P-PI3K, AKT, P-AKT, Bcl-2, and Bax proteins of rats in the hippocampal area were all determined by Western blot. RESULTS: Cognitive function was reduced and hippocampal neurons underwent apoptosis in the rats of the RIBI group, and cognitive abilities, histopathological alterations, and apoptosis of hippocampal neurons were significantly improved after BMSCs treatment; the expression of PI3K, P-PI3K, AKT, P-AKT, and Bcl-2 proteins, in the hippocampal region of the rat, was up-regulated, and Bax proteins were down-regulated. CONCLUSIONS: BMCSs can inhibit hippocampal neuronal apoptosis in RIBI, and the mechanism may be associated with the up-regulation of Bcl-2 and down-regulation of Bax by the PI3K/AKT signaling pathway.