Chitosan crosslinked flat scaffolds for peripheral nerve regeneration
Chitosan crosslinked flat scaffolds for peripheral nerve regeneration
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DOI：
10.1088/1748-6041/11/4/045010
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发表时间：
2016-08-01
影响因子：
4
通讯作者：
Raimondo, S.
中科院分区：
文献类型：
--
作者：
Fregnan, F.;Ciglieri, E.;Raimondo, S.
壳聚糖（CS）具有良好的生物相容性、生物可降解性、易获得性和抗菌活性，已被广泛应用于包括周围神经修复在内的多种生物医学领域。在这项研究中，CS平膜，交联与磷酸氢二钠（DSP）单独（CS/DSP）或与γ-缩水甘油氧基丙基三甲氧基硅烷（CS/GPTMS_DSP），与溶剂浇铸技术制造。通过选择交联剂和CS的配比，获得了既具有足够力学性能又具有良好生物相容性的复合材料，体外细胞毒性试验表明两种CS膜均能使细胞存活和增殖。此外，CS/GPTMS_DSP膜促进细胞粘附，诱导雪旺细胞样形态，并支持背根神经节外植体的神经突生长。对两种类型的神经支架进行了初步体内测试（CS/DSP和CS/GPTMS_DSP膜）证明了它们的潜力：（i）作为膜，通过端对端手术保护神经挤压或修复部位，并避免术后神经粘连;（ii）在大鼠正中神经缺损处，用CS/DSP和CS/GPTMS_DSP导管修复1cm的缺损，进一步研究其在体诱导神经再生的能力。CS/GPTMS_DSP管在缝合过程中变得更加脆弱，术后沿着12周，它们从远端神经残端脱离。相反，CS/DSP导管促进神经纤维再生和功能恢复，导致与自体移植修复正中神经相当的结果。
Chitosan (CS) has been widely used in a variety of biomedical applications, including peripheral nerve repair, due to its excellent biocompatibility, biodegradability, readily availability and antibacterial activity. In this study, CS flat membranes, crosslinked with dibasic sodium phosphate (DSP) alone (CS/DSP) or in association with the gamma-glycidoxypropyltrimethoxysilane (CS/GPTMS_DSP), were fabricated with a solvent casting technique. The constituent ratio of crosslinking agents and CS were previously selected to obtain a composite material having both adequate mechanical properties and high biocompatibility.In vitro cytotoxicity tests showed that both CS membranes allowed cell survival and proliferation. Moreover, CS/GPTMS_DSP membranes promoted cell adhesion, induced Schwann cell-like morphology and supported neurite outgrowth from dorsal root ganglia explants.Preliminary in vivo tests carried out on both types of nerve scaffolds (CS/DSP and CS/GPTMS_DSP membranes) demonstrated their potential for: (i) protecting, as a membrane, the site of nerve crush or repair by end-to-end surgery and avoiding post-operative nerve adhesion; (ii) bridging, as a conduit, the two nerve stumps after a severe peripheral nerve lesion with substance loss.A 1 cm gap on rat median nerve was repaired using CS/DSP and CS/GPTMS_DSP conduits to further investigate their ability to induce nerve regeneration in vivo. CS/GPTMS_DSP tubes resulted to be more fragile during suturing and, along a 12 week post-operative lapse of time, they detached from the distal nerve stump. On the contrary CS/DSP conduits promoted nerve fiber regeneration and functional recovery, leading to an outcome comparable to median nerve repaired by autograft.