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Controlled Release of Growth Factors from Multilayered Fibrous Scaffold for Functional Recoveries in Crushed Sciatic Nerve
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2018-01-23 00:00:00 , DOI: 10.1021/acsbiomaterials.7b00801
Min-Ho Hong 1 , Hye Jin Hong 2 , Haejeong Pang 2 , Hyo-Jung Lee 1 , Seong Yi 1 , Won-Gun Koh 2
Affiliation  

In this study, we designed and fabricated a multilayered fibrous scaffold capable of the controlled release of multiple growth factors for sciatic nerve regeneration in rats. The scaffold consists of three layers prepared by sequential electrospinning, where the first layer is fabricated using polycaprolactone (PCL)-aligned electrospun nanofibers for the attachment and differentiation of cells toward the direction of the sciatic nerve. The second and third layers are fabricated using poly(lactic-co-glycolic acid) 6535 (PLGA 6535) and 8515 (PLGA 8515), respectively. The resultant three nanofiber layers were stacked and fixed by incorporating hydrogel micropatterns at both ends of nanofiber scaffold, which also facilitated the surgical handling of the multilayered scaffolds. The PLGA layers acted as reservoirs to release growth factors neurotrophin (NT-3), brain-derived neurotrophic factor (BDNF), and platelet-derived growth factor (PDGF). The different biodegradation rate of each PLGA layer enabled the controlled release of multiple growth factors such as NT-3, BDNF, and PDGF with different patterns. In a rat model, the injured nerve was rolled up with the multilayered scaffold loading growth factors, and behavior tests were performed five weeks after surgery. Sciatic functional index (SFI) and mechanical allodynia analysis revealed that the fast release of NT-3 and BDNF from PLGA 6535 and subsequent slow release of PDGF from PLGA 8515 proved to be the greatest aid to neural tissue regeneration. In addition to the biochemical cues from growth factors, the aligned PCL layer that directly contacts the injured nerve could provide topographical stimulation, offering practical assistance to new tissue and cells for directional growth parallel to the sciatic nerve. This study demonstrated that our multilayered scaffold performs a function that can be used to promote locomotor activity and enhance nerve regeneration in combination with align-patterned topography and the controlled release of growth factors.

中文翻译:

受控释放来自多层纤维支架的生长因子,用于坐骨神经碎裂后的功能恢复

在这项研究中,我们设计和制造了多层纤维支架,能够控制多种生长因子的释放,从而促进大鼠坐骨神经的再生。支架由通过顺序电纺丝制备的三层组成,其中第一层使用聚己内酯(PCL)对齐的电纺纳米纤维制造,用于细胞朝坐骨神经方向的附着和分化。所述第二和第三层都使用聚(乳酸-制造-乙醇酸6535(PLGA 6535)和8515(PLGA 8515)。通过在纳米纤维支架的两端并入水凝胶微图案将所得的三个纳米纤维层堆叠并固定,这也促进了多层支架的手术处理。PLGA层充当储存器以释放生长因子神经营养蛋白(NT-3),脑源性神经营养因子(BDNF)和血小板源性生长因子(PDGF)。每个PLGA层的生物降解率不同,可以控制释放具有不同模式的多种生长因子,例如NT-3,BDNF和PDGF。在大鼠模型中,用多层支架负载生长因子将受伤的神经卷起来,并在手术后五周进行行为测试。坐骨神经功能指数(SFI)和机械异常性疼痛分析表明,从PLGA 6535中快速释放NT-3和BDNF,随后从PLGA 8515中缓慢释放PDGF,对神经组织再生具有最大的帮助。除了来自生长因子的生化线索外,直接接触受伤神经的对齐PCL层还可以提供地形刺激,为新组织和细胞平行于坐骨神经的定向生长提供实际帮助。这项研究表明,我们的多层支架与对齐模式的地形和生长因子的受控释放相结合,可以发挥促进运动活动和增强神经再生的功能。
更新日期:2018-01-23
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