A Bio and synthetic polymer based nerve guide tested under in vitro and in vivo conditions

Dursun Usal, Tuğba
Damages to the peripheral nervous system due to age, diseases or trauma may lead to gap formation in nervous tissue and inhibit signal transfer. Nerve guides are used to bridge the neural gaps created as a result of these events. This study describes the design, construction, and testing of a nerve guide which carries inner guidance elements to provide an appropriate microenvironment for peripheral nerve regeneration. A methacrylated gelatin-poly(2-hydroxyethyl methacrylate) (GelMA-pHEMA) hydrogel and 3D printed polycaprolactone (PCL) tube were produced as the exterior part of the nerve guide. Inner guidance elements, gelatin-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) aligned fibers, were produced to provide PC12 cell alignment. Both GelMA-pHEMA hydrogels and PCL tube were suitable for Schwann cell (SC) attachment and proliferation. PC12 cells, seeded on gelatin-PHBV aligned fibrous mats, were aligned along the fiber axis and showed neurite outgrowth. Gelatin-PHBV fibrous mats were rolled and implanted into the 3D printed PCL tube to obtain a whole nerve guide structure. Over three weeks, cell number increased significantly. SCs were attached to the PCL tube, connected to each other and showed myelination. PC12 cells were also attached, proliferated and migrated from proximal to distal part on the gelatin-PHBV aligned mats. The increase in expression of neuronal markers such as beta-III tubulin and NeuN indicated the differentiation of PC12 cells into neurons. This composite nerve guide was tested under in vivo conditions. 10 mm sciatic nerve defect was created in rats and different types of nerve guides were implanted at the injury site. Both walking track analysis and electrophysiology studies showed that there is a functional recovery in the groups having PCL tube and PCL tube with gelatin-PHBV mat and SCs. These results show the potential of the developed nerve guide for the peripheral nerve regeneration under in vitro and in vivo conditions.


Arslantunalı Şahin, Damla; Son, Çağdaş Devrim; Hasırcı, Vasıf Nejat; Department of Biotechnology (2022-2-1)
Any injury in peripheral nerves may result in a loss of neuronal communication along sensory and motor nerves, affecting patients’ daily activities. Today, there are various FDA approved commercial conduit materials; hollow tubes preventing them from used in gaps bigger than 10 mm, because they may lead axonal sprouts to form. The presented study includes pHEMA wrapping structure filled with GelMA-HaMA gel matrix as a nerve guidance channel. Following the structural analysis of the nerve guide, in vitro stu...
A novel GeIMA-pHEMA hydrogel nerve guide for the treatment of peripheral nerve damages
DURSUN USAL, TUĞBA; Yucel, Deniz; Hasırcı, Vasıf Nejat (2019-01-01)
Damage to the nervous system due to age, diseases or trauma may inhibit signal transfer along the nervous system. Nerve guides are used to treat these injuries by bridging the proximal and the distal end together. The design of the guide is very important for the reconnection of the severed axons. Methacrylated gelatin-poly(2-hydroxyethylmethacrylate) (GeIMA-pHEMA) hydrogel was produced as the outer part of the nerve guide. pHEMA was added in various amounts into GeIMA and increased the mechanical strength ...
Differentiation of BMSCs into Nerve Precursor Cells on Fiber-Foam Constructs for Peripheral Nerve Tissue Engineering
Dursun Usal, Tuğba; YÜCEL, DENİZ; Hasırcı, Vasıf Nejat (2018-06-01)
Bone marrow stem cells (BMSCs) are frequently used in nerve tissue engineering studies due to ease of their isolation and high potential for differentiation into nerve cells. A bilayer fiber-foam construct containing nanofibrous elements to house and guide BMSCs was designed as a model to study the regeneration of damaged peripheral nerve tissue and eventually serve as a nerve guide. The construct consisted of a) a macroporous bottom layer to serve as the backing and support, and for nutrient transport, and...
Multiwalled CNT-pHEMA composite conduit for peripheral nerve repair.
Arslantunalı Şahin, Damla; Hasırcı, Vasıf Nejat (2014-03-01)
A nerve conduit is designed to improve peripheral nerve regeneration by providing guidance to the nerve cells. Conductivity of such guides is reported to enhance this process. In the current study, a nerve guide was constructed from poly(2-hydroxyethyl methacrylate) (pHEMA), which was loaded with multiwalled carbon nanotubes (mwCNT) to introduce conductivity. PHEMA hydrogels were designed to have a porous structure to facilitate the transportation of the compounds needed for cell nutrition and growth and al...
Peripheral nerve conduits: Technology update
Hasırcı, Nesrin; Arslantunalı Şahin, Damla; Hasırcı, Vasıf Nejat (2014-12-01)
Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allograf...
Citation Formats
T. Dursun Usal, “A Bio and synthetic polymer based nerve guide tested under in vitro and in vivo conditions,” Thesis (Ph.D.) -- Graduate School of Natural and Applied Sciences. Biotechnology., Middle East Technical University, 2019.