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Peripheral nerve regeneration following injury is often incomplete, resulting in significant personal and socioeconomic costs. Nerve conduits have been developed to complement or replace autologous nerve grafts. In this study, repairing injured peripheral nerves in rats is investigated by fabricating poly(D, l -lactic acid) (PDLLA)/β-tricalcium phosphate (β-TCP) nerve conduits filled by injectable chitosan (CS)-hyaluronic acid (HA) hydrogels featuring sustained release of nerve growth factor (NGF). All CS-HA hydrogels have porosities higher than 80%. The mass loss of the CS-HA hydrogels reaches 70% in 8 weeks. In vitro experiments suggest that the CS-HA/NGF hydrogels are suitable for the adhesion, spreading, and differentiation of neuronal cells, which also allow for sustained release of NGF. In vivo studies on the repair of 10-mm sciatic nerve defects in rats are used to assess nerve repair rate through walking track analysis, gastrocnemius weight analysis, and histological analysis. It is shown that the PDLLA/β-TCP nerve conduits laden with CS-HA/NGF hydrogels have a significant positive effect on the axon regeneration and myelination, compared to the PDLLA/β-TCP hollow nerve conduits and the autograft group. These results show that the CS-HA/NGF injectable hydrogel can effectively promote nerve regeneration making it a good candidate in the field of neural tissue engineering.

The aim of this study was to obtain the fillers in the lumen of hollow nerve conduits (NCs) to improve the microenvironment of nerve regeneration. A pH-induced injectable chitosan (CS)-hyaluronic acid (HA) hydrogel for nerve growth factor (NGF) sustained release was developed. Its properties were characterized by gelation time, FT-IR, SEM, in vitro swelling and degradation. Furthermore, the in vitro NGF release profiles and cell biocompatibility were also investigated. The experimental results show that the CS-HA aqueous solution can undergo a rapid gelation 3 minutes after its environmental pH is changed to 7.4. The CS-HA hydrogel has interconnected channels with a controllable pore diameter and with a porosity of about 80%. It has a favorable swelling behavior and can be degraded by about 70% within 8 weeks in vitro and is suitable for NGF release. The CS-HA/NGF hydrogel exhibits a lower cytotoxicity and is in favor of the adhesion and proliferation of the BMMSCs cells. It is indicated that the CS-HA/NGF will be a promising candidate for neural tissue engineering.

The usage of hollow nerve conduits shows inferior recovery effect on the repair of peripheral nerve defects. In this study, a biocompatible and biodegradable pH-induced injectable chitosan–hyaluronic acid hydrogel for nerve growth factor encapsulation and sustained release was developed as the fillers in the lumen of hollow nerve conduit to reform its microenvironment for peripheral nerve regeneration. The physicochemical properties of hydrogel were characterized by gelation time, Fourier transform infrared spectroscopy, scanning electron microscopy, compressive modulus, porosity, swelling ratio, and in vitro degradation. The in vitro nerve growth factor release profiles and cell evaluation were also investigated. The results show that the structure of chitosan–hyaluronic acid hydrogel is composed of interconnected channels with a controllable pore diameter ranging from 20 to 100 µm. The hydrogel can be degraded more than 70% within 8 weeks in vitro and is available for nerve growth factor sustained release. The chitosan–hyaluronic acid/nerve growth factor hydrogel is non-toxic and suitable for adhesion and proliferation of nerve cells and capable of maintaining nerve growth factor activity. Therefore, it could be a promising intraluminal filler of nerve conduits for peripheral nerve regeneration in neural tissue engineering.

A dual-receptor targeting delivery system based on mesoporous silica nanoparticles modified with hyaluronic acid and RGD peptide (MSNs/NH2–HA–RGD) was developed in the present study, and characterized by TEM, SAXRD, nitrogen adsorption–desorption analysis, DLS, FT-IR, 13C NMR and UV-vis. The results showed that MSNs/NH2–HA–RGD had an ideal monodispersibility, uniform particle size (172.5 ± 10 nm) and well-defined mesoporous structure. Moreover, cellular uptake results showed that MSNs/NH2–HA–RGD had an ideal dual-receptor mediated endocytosis pathway and could be significantly internalized into ovarian cancer cells. Chlorambucil (CHL), an anticancer drug, was chosen as a model drug to investigate drug loading, in vitro drug release behaviors and cytotoxicity. The results showed that CHL-loaded MSNs/NH2–HA–RGD exhibited a high drug loading capacity of about 10.1% and pH-sensitive drug controlled release behaviors. The cytotoxicity test showed that CHL-loaded MSNs/NH2–HA–RGD had a stronger cytotoxicity for ovarian cancer cells than one receptor or no receptor modified MSNs. It is expected that MSNs/NH2–HA–RGD may be a prospective candidate for targeted delivery of anticancer drugs to cancer foci.