The primary objective of this study was to offer a thorough examination of the various tissue engineering approaches employed in sciatic nerve repair. Investigating scaffold-based techniques, cell-based therapies, and bioactive molecule delivery systems shed light on the strengths, limitations, and challenges associated with each method.
A systematic literature search was conducted to identify relevant studies published up to the date of this review. Databases such as PubMed, Web of Science, and Scopus were used to gather a diverse range of articles, including original research, clinical trials, and review papers.
Promising materials for neural tissue engineering include scaffolds, such as chitosan, collagen, and synthetic polymers. Moreover, cell-based therapies using neural crest stem cells, adipose-derived stem cells, and bone marrow-derived mesenchymal stem cells the potential to promote peripheral nerve regeneration. Delivery systems, such as neurotrophic factor-loaded microspheres and exosomes, along with neurotrophic factors, such as NGF, BDNF, and GDNF, have demonstrated promising results for enhancing sciatic nerve repair.
Stem cells hold potential for nerve tissue repair, whereas controlled release of neurotrophic factors aids axonal regeneration. Overcoming challenges such as optimal implantation timing and minimizing secondary damage is crucial and ongoing research is needed to refine scaffold properties and improve distal pathway efficacy, ultimately enhancing surgical management and functional recovery for patients with severe peripheral nerve injuries.
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As a review manuscript, this article does not involve original data collection or analysis. Instead, it is a comprehensive synthesis and analysis of existing literature and information from publicly available sources. All references used in this review article are appropriately cited and acknowledged. Therefore, no specific datasets are associated with this review, and there are no additional data files to be shared.
Aebischer, P., Salessiotis, A., & Winn, S. (1989). Basic fibroblast growth factor released from synthetic guidance channels facilitates peripheral nerve regeneration across long nerve gaps. Journal of Neuroscience Research, 23(3), 282–289.
Angius, D., Wang, H., Spinner, R. J., Gutierrez-Cotto, Y., Yaszemski, M. J., & Windebank, A. J. (2012). A systematic review of animal models used to study nerve regeneration in tissue-engineered scaffolds. Biomaterials, 33(32), 8034–8039.
Baudequin, T., & Tabrizian, M. (2018). Multilineage constructs for scaffold-based tissue engineering: A review of tissue-specific challenges. Advanced Healthcare Materials, 7(3), 1700734.
Boyd, J. G., & Gordon, T. (2003). Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury. Molecular Neurobiology, 27, 277–323.
Bucan, V., Vaslaitis, D., Peck, C.-T., Strauß, S., Vogt, P. M., & Radtke, C. (2019). Effect of exosomes from rat adipose-derived mesenchymal stem cells on neurite outgrowth and sciatic nerve regeneration after crush injury. Molecular Neurobiology, 56, 1812–1824.
Cao, J., Sun, C., Zhao, H., Xiao, Z., Chen, B., Gao, J., Zheng, T., Wu, W., Wu, S., & Wang, J. (2011). The use of laminin modified linear ordered collagen scaffolds loaded with laminin-binding ciliary neurotrophic factor for sciatic nerve regeneration in rats. Biomaterials, 32(16), 3939–3948.
Ding, T., Luo, Z.-J., Zheng, Y., Hu, X.-Y., & Ye, Z.-X. (2010). Rapid repair and regeneration of damaged rabbit sciatic nerves by tissue-engineered scaffold made from nano-silver and collagen type I. Injury, 41(5), 522–527.
Emamgholi, A., Rahimi, M., Kaka, G., Sadraie, S. H., & Najafi, S. (2015). Presentation of a novel model of chitosan-polyethylene oxide-nanohydroxyapatite nanofibers together with bone marrow stromal cells to repair and improve minor bone defects. Iranian Journal of Basic Medical Sciences, 18(9), 887.
Frattini, F., Pereira Lopes, F. R., Almeida, F. M., Rodrigues, R. F., Boldrini, L. C., Tomaz, M. A., Baptista, A. F., Melo, P. A., & Martinez, A. M. B. (2012). Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve regeneration and sensory neuron survival after nerve injury. Tissue Engineering Part A, 18(19–20), 2030–2039.
Giuffre, B. A., & Jeanmonod, R. (2018). Anatomy, sciatic nerve. Treasure Island (FL): StatPearls Publishing 2022.
Goodrich, J. T., & Kliot, M. (2015). History of the peripheral and cranial nerves. Nerves and Nerve Injuries, 2015, 3–22.
Gu, X. (2015). Progress and perspectives of neural tissue engineering. Frontiers of Medicine, 9, 401–411.
Gu, X., Ding, F., & Williams, D. F. (2014). Neural tissue engineering options for peripheral nerve regeneration. Biomaterials, 35(24), 6143–6156.
Hadlock, T. A., Sheahan, T., Cheney, M. L., Vacanti, J. P., & Sundback, C. A. (2003). Biologic activity of nerve growth factor slowly released from microspheres. Journal of Reconstructive Microsurgery, 19(03), 179–184.
Ho, P.-R., Coan, G. M., Cheng, E. T., Niell, C., Tarn, D. M., Zhou, H., Sierra, D., & Terris, D. J. (1998). Repair with collagen tubules linked with brain-derived neurotrophic factor and ciliary neurotrophic factor in a rat sciatic nerve injury model. Archives of Otolaryngology-Head & Neck Surgery, 124(7), 761–766.
Huang, J., Lu, L., Zhang, J., Hu, X., Zhang, Y., Liang, W., & W, Siyu., Luo, Z. (2012). Electrical stimulation to conductive scaffold promotes axonal regeneration and remyelination in a rat model of large nerve defect. PLoS One, 7(6), e39526.
Hudson, T. W., Liu, S. Y., & Schmidt, C. E. (2004). Engineering an improved acellular nerve graft via optimized chemical processing. Tissue Engineering, 10(9–10), 1346–1358.
Ijpma, F., Van De Graaf, R., & Meek, M. (2008). The early history of tubulation in nerve repair. Journal of Hand Surgery (European Volume), 33(5), 581–586.
Ikada, Y. (2006). Challenges in tissue engineering. Journal of the Royal Society Interface, 3(10), 589–601.
Jahromi, M., Razavi, S., Seyedebrahimi, R., Reisi, P., & Kazemi, M. (2021). Regeneration of rat sciatic nerve using PLGA conduit containing rat ADSCs with controlled release of BDNF and gold nanoparticles. Journal of Molecular Neuroscience, 71, 746–760.
Jaing, T.-H. (2014). Umbilical cord blood: A trustworthy source of multipotent stem cells for regenerative medicine. Cell Transplantation, 23(4–5), 493–496.
Jia, H., Wang, Y., Tong, X. J., Liu, G. B., Li, Q., Zhang, L. X., & Sun, X. H. (2012). Sciatic nerve repair by acellular nerve xenografts implanted with BMSCs in rats xenograft combined with BMSCs. Synapse (New York, NY), 66(3), 256–269.
Kaka, G., Arum, J., Sadraie, S. H., Emamgholi, A., & Mohammadi, A. (2017). Bone marrow stromal cells associated with poly l-lactic-co-glycolic acid (PLGA) nanofiber scaffold improve transected sciatic nerve regeneration. Iranian Journal of Biotechnology, 15(3), 149.
Kemp, S. W., Walsh, S. K., & Midha, R. (2008). Growth factor and stem cell enhanced conduits in peripheral nerve regeneration and repair. Neurological Research, 30(10), 1030–1038.
Labroo, P., Shea, J., Edwards, K., Ho, S., Davis, B., Sant, H., I, Goodwin, I., Gale, B., & Agarwal, J. (2017). Novel drug delivering conduit for peripheral nerve regeneration. Journal of Neural Engineering, 14(6), 066011.
Lackington, W. A., Kočí, Z., Alekseeva, T., Hibbitts, A. J., Kneafsey, S. L., Chen, G., & O’Brien, F. J. (2019). Controlling the dose-dependent, synergistic and temporal effects of NGF and GDNF by encapsulation in PLGA microparticles for use in nerve guidance conduits for the repair of large peripheral nerve defects. Journal of Controlled Release, 304, 51–64.
Li, R., Li, D.-H., Zhang, H.-Y., Wang, J., Li, X.-K., & Xiao, J. (2020). Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration. Acta Pharmacologica Sinica, 41(10), 1289–1300.
Li, R., Li, Y., Wu, Y., Zhao, Y., Chen, H., Yuan, Y., Xu, K., Lu, Y., Wang, J., Li, X., & Jia, X. (2018). Heparin-poloxamer thermosensitive hydrogel loaded with bFGF and NGF enhances peripheral nerve regeneration in diabetic rats. Biomaterials, 168, 24–37.
Li, Y., Lv, S., Yuan, H., Ye, G., Mu, W., Fu, Y., Zhang, X., Feng, Z., & Chen, W. (2021). Peripheral nerve regeneration with 3D printed bionic scaffolds loading neural crest stem cell derived Schwann cell progenitors. Advanced Functional Materials, 31(16), 2010215.
Li, Y., Ma, Z., Ren, Y., Lu, D., Li, T., Li, W., Wang, J., Ma, H., & Zhao, J. (2021). Tissue engineering strategies for peripheral nerve regeneration. Frontiers in Neurology, 12, 768267.
Liu, H., Zhou, Y., Chen, S., Bu, M., Xin, J., & Li, S. (2013). Current sustained delivery strategies for the design of local neurotrophic factors in treatment of neurological disorders. Asian Journal of Pharmaceutical Sciences, 8(5), 269–277.
Madduri, S., Feldman, K., Tervoort, T., Papaloïzos, M., & Gander, B. (2010). Collagen nerve conduits releasing the neurotrophic factors GDNF and NGF. Journal of Controlled Release, 143(2), 168–174.
Madduri, S., & Gander, B. (2012). Growth factor delivery systems and repair strategies for damaged peripheral nerves. Journal of Controlled Release, 161(2), 274–282.
Meena, P., Kakkar, A., Kumar, M., Khatri, N., Nagar, R. K., Singh, A., Malhotra, P., Shukla, M., Saraswat, S. K., Srivastava, S., Datt, R., & Pandey, S. (2021). Advances and clinical challenges for translating nerve conduit technology from bench to bed side for peripheral nerve repair. Cell and Tissue Research, 383(2), 617–644.
Mohamadi, F., Ebrahimi-Barough, S., Nourani, M. R., Ahmadi, A., & Ai, J. (2018). Use new poly (ε-caprolactone/collagen/NBG) nerve conduits along with NGF for promoting peripheral (sciatic) nerve regeneration in a rat. Artificial Cells, Nanomedicine, and Biotechnology, 46(sup2), 34–45.
Nagase, T., Matsumoto, D., Nagase, M., Yoshimura, K., Shigeura, T., Inoue, M., Hasegawa, M., Yamagishi, M., & Machida, M. (2007). Neurospheres from human adipose tissue transplanted into cultured mouse embryos can contribute to craniofacial morphogenesis: a preliminary report. Journal of Craniofacial Surgery, 18(1), 49–53.
Péan, J.-M., Menei, P., Morel, O., Montero-Menei, C. N., & Benoit, J.-P. (2000). Intraseptal implantation of NGF-releasing microspheres promote the survival of axotomized cholinergic neurons. Biomaterials, 21(20), 2097–2101.
Pfister, B. J., Gordon, T., Loverde, J. R., Kochar, A. S., Mackinnon, S. E., & Cullen, D. K. (2011). Biomedical engineering strategies for peripheral nerve repair: Surgical applications, state of the art, and future challenges. Critical Reviews™ in Biomedical Engineering, 39(2), 81–124.
Piquilloud, G., Christen, T., Pfister, L. A., Gander, B., & Papaloïzos, M. Y. (2007). Variations in glial cell line-derived neurotrophic factor release from biodegradable nerve conduits modify the rate of functional motor recovery after rat primary nerve repairs. European Journal of Neuroscience, 26(5), 1109–1117.
Rao, F., Wang, Y., Zhang, D., Lu, C., Cao, Z., Sui, J., Wu, M., Zhang, Y., Pi, W., Kou, Y., Wang, X., Zhang, P., & Wang, B. (2020). Aligned chitosan nanofiber hydrogel grafted with peptides mimicking bioactive brain-derived neurotrophic factor and vascular endothelial growth factor repair long-distance sciatic nerve defects in rats. Theranostics, 10(4), 1590.
Reid, A. J., de Luca, A. C., Faroni, A., Downes, S., Sun, M., Terenghi, G., & Kingham, P. J. (2013). Long term peripheral nerve regeneration using a novel PCL nerve conduit. Neuroscience Letters, 544, 125–130.
Ribeiro, F. S., Bettencourt Pires, M. A., da Silva Junior, E. X., Casal, D., Casanova-Martinez, D., Pais, D., & Goyri-O’Neill, J. E. (2018). Rethinking sciatica in view of a bilateral anatomical variation of the sciatic nerve, with low origin and high division: Historical, anatomical and clinical approach. Acta Medica Portuguesa, 31(10), 568–575.
Saadai, P., Wang, A., Nout, Y. S., Downing, T. L., Lofberg, K., Beattie, M. S., Bresnahan, J. C., & Farmer, D. L. (2013). Human induced pluripotent stem cell-derived neural crest stem cells integrate into the injured spinal cord in the fetal lamb model of myelomeningocele. Journal of Pediatric Surgery, 48(1), 158–163.
Salehi, M., Bagher, Z., Kamrava, S. K., Ehterami, A., Alizadeh, R., Farhadi, M., Falah, M., & Komeili, A. (2019). Alginate/chitosan hydrogel containing olfactory ectomesenchymal stem cells for sciatic nerve tissue engineering. Journal of Cellular Physiology, 234(9), 15357–15368.
Sen, S. K., Lowe, J. B., III., Brenner, M. J., Hunter, D. A., & Mackinnon, S. E. (2005). Assessment of the immune response to dose of nerve allografts. Plastic and Reconstructive Surgery, 115(3), 823–830.
Siemionow, M., & Brzezicki, G. (2009). Current techniques and concepts in peripheral nerve repair. International Review of Neurobiology, 87, 141–172.
Veron, A. D., Bienboire-Frosini, C., Girard, S. D., Sadelli, K., Stamegna, J.-C., Khrestchatisky, M., Alexis, J., Pageat, P., & Mengoli, M. (2018). Syngeneic transplantation of olfactory ectomesenchymal stem cells restores learning and memory abilities in a rat model of global cerebral ischemia. Stem Cells International, 2018, 2683969.
Vijayavenkataraman, S. (2020). Nerve guide conduits for peripheral nerve injury repair: A review on design, materials and fabrication methods. Acta Biomaterialia, 106, 54–69.
Wang, C.-Y., Liu, J.-J., Fan, C.-Y., Mo, X.-M., Ruan, H.-J., & Li, F.-F. (2012). The effect of aligned core–shell nanofibres delivering NGF on the promotion of sciatic nerve regeneration. Journal of Biomaterials Science, Polymer Edition, 23(1–4), 167–184.
Wang, Y., Yu, T., & Hu, F. (2022). Hypocapnia stimuli-responsive engineered exosomes delivering miR-218 facilitate sciatic nerve regeneration. Frontiers in Bioengineering and Biotechnology, 10, 825146.
Xu, X., Yu, H., Gao, S., Mao, H.-Q., Leong, K. W., & Wang, S. (2002). Polyphosphoester microspheres for sustained release of biologically active nerve growth factor. Biomaterials, 23(17), 3765–3772.
Xue, C., Zhu, H., Tan, D., Ren, H., Gu, X., Zhao, Y., Zhang, P., Sun, Z., Yang, Y., & Gu, J. (2018). Electrospun silk fibroin-based neural scaffold for bridging a long sciatic nerve gap in dogs. Journal of Tissue Engineering and Regenerative Medicine, 12(2), e1143–e1153.
Yu, W., Zhao, W., Zhu, C., Zhang, X., Ye, D., Zhang, W., Zhou, Y., Jiang, X., & Zhang, Z. (2011). Sciatic nerve regeneration in rats by a promising electrospun collagen/poly(ε-caprolactone) nerve conduit with tailored degradation rate. BMC Neuroscience, 12(1), 68. https://doi.org/10.1186/1471-2202-12-68
Yuan, Y., Zhang, P., Yang, Y., Wang, X., & Gu, X. (2004). The interaction of Schwann cells with chitosan membranes and fibers in vitro. Biomaterials, 25(18), 4273–4278.
Yurie, H., Ikeguchi, R., Aoyama, T., Kaizawa, Y., Tajino, J., Ito, A., Ohta, S., Oda, H., Takeuchi, H., Akieda, S., Tsuji, M., Nakayama, K., & Matsuda, S. (2017). The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model. PLoS One, 12(2), e0171448.
Zhang, J., Zhang, Y., Jiang, Y. K., Li, J. A., Wei, W. F., Shi, M. P., Wang, Y. B., & Jia, G. L. (2022). The effect of poly (lactic-co-glycolic acid) conduit loading insulin-like growth factor 1 modified by a collagen-binding domain on peripheral nerve injury in rats. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 110(9), 2100–2109.
Zurita, M., Vaquero, J., Oya, S., Bonilla, C., & Aguayo, C. (2007). Neurotrophic Schwann-cell factors induce neural differentiation of bone marrow stromal cells. NeuroReport, 18(16), 1713–1717.
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Ebrahimi-kia, Y., Davoudi, P. & Bordbar, S. Tissue Engineering for Sciatic Nerve Repair: Review of Methods and Challenges. J. Med. Biol. Eng. (2023). https://doi.org/10.1007/s40846-023-00833-9