Zennifer Allen, Praveenn Kumar S K, Bagewadi Shambhavi, Unnamalai Swathi, Chellappan Davidraj, Abdulmalik Sama, Yu Xiaojun, Sethuraman Swaminathan, Sundaramurthi Dhakshinamoorthy, Kumbar Sangamesh G
Tissue Engineering & Additive Manufacturing (TEAM) Lab, Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA Deemed University, Tamil Nadu, India.
Department of Orthopedic Surgery, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030-4037, USA.
Bioact Mater. 2024 Nov 7;44:544-557. doi: 10.1016/j.bioactmat.2024.10.028. eCollection 2025 Feb.
Large-gap nerve defects require nerve guide conduits (NGCs) for complete regeneration and muscle innervation. Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration. Still, most are tubular with inadequate pore sizes and lack surface cues for nutrient transport, cell attachment, and tissue infiltration. This study developed a porous spiral NGC to address these issues using a 3D-printed thermoplastic polyurethane (TPU) fiber lattice. The lattice was functionalized with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) electrospun aligned (aPHBV) and randomly (rPHBV) oriented nanofibers to enhance cellular activity. TPU lattices were made with 25 %, 35 %, and 50 % infill densities to create scaffolds with varied mechanical compliance. The fabricated TPU/PHBV spiral conduits had significantly higher surface areas (25 % TPU/PHBV: 698.97 mm, 35 % TPU/PHBV: 500.06 mm, 50 % TPU/PHBV: 327.61 mm) compared to commercially available nerve conduits like Neurolac™ (205.26 mm). Aligned PHBV nanofibers showed excellent Schwann cell (RSC96) adhesion, proliferation, and neurogenic gene expression for all infill densities. Spiral TPU/PHBV conduits with 25 % and 35 % infill densities exhibited Young's modulus values comparable to Neurotube® and ultimate tensile strength like acellular cadaveric human nerves. A 10 mm sciatic nerve defect in Wistar rats treated with TPU/aPHBV NGCs demonstrated muscle innervation and axon healing comparable to autografts over 4 months, as evaluated by gait analysis, functional recovery, and histology. The TPU/PHBV NGC developed in this study shows promise as a treatment for large-gap nerve defects.
大间隙神经缺损需要神经引导导管（NGC）来实现完全再生和肌肉神经支配。人们已经采用各种支架设计和组织工程策略开发了许多NGC，以促进轴突再生。然而，大多数是管状的，孔径不足，并且缺乏用于营养物质运输、细胞附着和组织浸润的表面线索。本研究使用3D打印的热塑性聚氨酯（TPU）纤维晶格开发了一种多孔螺旋NGC来解决这些问题。该晶格用聚（3-羟基丁酸酯-共-3-羟基戊酸酯）（PHBV）静电纺丝排列（aPHBV）和随机（rPHBV）取向的纳米纤维进行功能化处理，以增强细胞活性。TPU晶格以25%、35%和50%的填充密度制成，以创建具有不同机械顺应性的支架。与Neurolac™ 等市售神经导管（205.26平方毫米）相比，制造的TPU/PHBV螺旋导管具有显著更高的表面积（25% TPU/PHBV：698.97平方毫米，35% TPU/PHBV：500.06平方毫米，50% TPU/PHBV：327.61平方毫米）。对于所有填充密度，排列的PHBV纳米纤维均显示出优异的雪旺细胞（RSC96）粘附、增殖和神经源性基因表达。填充密度为25%和35%的螺旋TPU/PHBV导管表现出与Neurotube®相当的杨氏模量值以及与无细胞尸体人神经相当的极限拉伸强度。通过步态分析、功能恢复和组织学评估，用TPU/aPHBV NGC治疗的Wistar大鼠10毫米坐骨神经缺损在4个月内显示出与自体移植相当的肌肉神经支配和轴突愈合。本研究中开发的TPU/PHBV NGC有望成为治疗大间隙神经缺损的方法。
