Escobar Ane, Carvalho Mariana R, Silva Tiago H, Reis Rui L, Oliveira J Miguel
3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.
ICVS/3B's-PT Government Associate Laboratory, 4710-057 Braga, Braga Portugal.
In Vitro Model. 2023 Apr 18;2(5):195-205. doi: 10.1007/s44164-023-00050-3. eCollection 2023 Nov.
Peripheral nerve injuries represent a major clinical challenge, if nerve ends retract, there is no spontaneous regeneration, and grafts are required to proximate the nerve ends and give continuity to the nerve. The nerve guidance conduits (NGCs) presented in this work are silk fibroin (SF)-based, which is biocompatible and very versatile. The formation of conduits is obtained by forming a covalently cross-linked hydrogel in two concentric moulds, and the inner longitudinally aligned pattern of the SF NGCs is obtained through the use of a patterned inner mould. SF NGCs with two wall thicknesses of ~ 200 to ~ 400 μm are synthesized. Their physicochemical and mechanical characteristics have shown improved properties when the wall thickness is thicker such as resistance to kinking, which is of special importance as conduits might also be used to substitute nerves in flexible body parts. The Young modulus is higher for conduits with inner pattern, and none of the conduits has shown any salt deposition in presence of simulated body fluid, meaning they do not calcify; thus, the regeneration does not get impaired when conduits have contact with body fluids. In vitro studies demonstrated the biocompatibility of the SF NGCs; proliferation is enhanced when iSCs are cultured on top of conduits with longitudinally aligned pattern. BJ fibroblasts cannot infiltrate through the SF wall, avoiding scar tissue formation on the lumen of the graft when used in vivo. These conduits have been demonstrated to be very versatile and fulfil with the requirements for their use in PNR.
The online version contains supplementary material available at 10.1007/s44164-023-00050-3.
周围神经损伤是一项重大的临床挑战，如果神经末梢回缩，就不会有自发再生，需要移植来使神经末梢靠近并使神经保持连续性。本研究中提出的神经引导导管（NGC）是以丝素蛋白（SF）为基础的，丝素蛋白具有生物相容性且用途广泛。通过在两个同心模具中形成共价交联水凝胶来制备导管，通过使用有图案的内模获得SF NGC的内部纵向排列图案。合成了两种壁厚约为200至400μm的SF NGC。当壁厚增加时，它们的物理化学和机械特性表现出改善的性能，如抗扭结能力，这在导管也可能用于替代灵活身体部位的神经时尤为重要。具有内部图案的导管的杨氏模量更高，并且在模拟体液存在的情况下，没有任何导管显示出盐沉积，这意味着它们不会钙化；因此，当导管与体液接触时，再生不会受到损害。体外研究证明了SF NGC的生物相容性；当诱导性多能干细胞（iSCs）在具有纵向排列图案的导管顶部培养时，增殖会增强。BJ成纤维细胞不能穿透SF壁，在体内使用时可避免在移植物管腔内形成瘢痕组织。这些导管已被证明用途广泛，满足周围神经修复（PNR）的使用要求。
在线版本包含可在10.1007/s44164-023-00050-3获取的补充材料。
