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Currently commercially available nerve conduits have demonstrated suboptimal clinical efficacy in repairing peripheral nerve defects. Although tissue-engineered nerve grafts (TENGs) with sustained release of neurotrophic factors (NTFs) are experimentally proved to be more effective than these blank conduits, there remains a lack of clinical translation. NTFs are typically immobilized onto scaffold materials of the conduit via adsorption, specific binding or other incorporation techniques. These scaffold-based delivery strategies increase complexity and cost of conduit fabrication and lack flexibility in choosing different drugs. Therefore, to facilitate clinical translation and commercialization, we construct a TENG using a scaffold-independent drug delivery system (DDS). Approach: This study adopted a scaffold-independent DDS based on methoxy-poly(ethylene glycol)-b-poly(γ-ethyl-L-glutamate) (mPEG-PELG) thermosensitive hydrogels that undergo sol-to-gel transition at body temperature. In addition, TENG, a chitosan scaffold filled with nerve growth factor (NGF)-loaded mPEG-PELG that gel in the lumen upon injection during surgery and function as a drug-releasing conduit-filler, was designed. Subsequently, the efficacy of DDS and therapeutic effects of TENG were assessed. Main results: The results demonstrated that NGF-loaded mPEG-PELG controllably and sustainably released bioactive NGF for 28 days. When bridging a 10 mm rat sciatic nerve gap, the morphological, electrophysiological, and functional analyses revealed that NGF-releasing TENG (Scaffold+NGF/mPEG-PELG) achieved superior regenerative outcomes compared to plain scaffolds and those combined with systemic delivery of NGF (daily intramuscular injection), and its effects were relatively similar to autografts. Significance: This study has proposed a TENG using thermosensitive hydrogels as an injectable implant to controllably release NGF, which has promising therapeutic potential and translatability. Such TENGs obviate the need for conduit modification, complex preloading or binding mediators, therefore they allow the ease of drug switching in clinical practice and greatly simplify the manufacturing process due to the independent preparation of drug delivery system.
This article was published in the following journal.
Name: Journal of neural engineering
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Phenomenon which occurs in certain tissue sites and organs (e.g., the ANTERIOR CHAMBER and CORNEA of the eye, brain PARENCHYMAL TISSUE and fetus) to tolerate a known antigen, thereby suppressing the inflammatory immune response. Foreign tissue grafts survive for prolonged periods when placed within such immune privileged sites and organs.
Procedures that stimulate nerve elongation over a period of time. They are used in repairing nerve tissue.
Differentiated tissue of the central nervous system composed of NERVE CELLS, fibers, DENDRITES, and specialized supporting cells.
Neoplasms composed of nerve tissue. This concept does not refer to neoplasms located in the nervous system or its component nerves.
The shortest duration of an electrical stimulus where the threshold amplitude is twice the rheobase - the minimum required for eliciting an ACTION POTENTIAL at any time period. It is a measure of the excitability of nerve or muscle tissue, and is characteristic of types and/or condition of the nerve or muscle cells in the tissue.
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