Preparation and Evaluation of an Injectable Chitosan-Hyaluronic Acid hydrogel for Peripheral Nerve Regeneration

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 p H-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 p H is changed to 7.4. The CSHA 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.

Platelet-rich plasma combined with injectable hyaluronic acid hydrogel for porcine cartilage regeneration: a 6-month follow-up

Based on our previous study,the utilization of an ultraviolet light photo-cross-linkable hyaluronic acid(HA)hydrogel integrated with a small molecule kartogenin-encapsulated nanoparticles obtained good reconstruction of osteochondral defects in a rabbit model,indicating the superiority of injectable hydrogel-based scaffolds in cartilage tissue engineering.Platelet-rich plasma(PRP),rich in various growth factors,proteins and cytokines,is considered to facilitate cartilage healing by stimulating cell proliferation and inducing chondrogenesis in cartilage defect site.The aim of this study was to test the therapeutic feasibility of autologous PRP combined with injectable HA hydrogel on cartilage repair.The focal cartilage defects with different critical sizes in the medial femoral condyle of a porcine model were used.At 6 months,the minipigs were sacrificed for assessment of macroscopic appearance,magnetic resonance imaging,micro-computed tomography,histology staining and biomechanics.The HA hydrogel combined with PRP-treated group showed more hyaline-like cartilage exhibited by macroscopic appearance and histological staining in terms of extracellular matrix and type II collagen without formation of hypertrophic cartilage,indicating its capacity to improve cartilage healing in the minipig model evaluated at 6 months,with full-thickness cartilage defect of 8.5mm diameter and osteochondral defect of 6.5mm diameter,5mm depth exhibiting apparent regeneration.

Versatile dopamine-functionalized hyaluronic acid-recombinant human collagen hydrogel promoting diabetic wound healing via inflammation control and vascularization tissue regeneration

The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing,delayed healing,susceptibility to infection,and elevated risk of reopening,highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels.Here,we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III(rhCol)by oxidative coupling of the catechol group using the H_(2)O_(2)/HRP catalytic system.The post-reactive hydrogel has a good porous structure,swelling rate,reasonable degradation,rheological and mechanical properties,and the catechol group and dopamine impart to the hydrogel tissue adhesiveness,antioxidant capacity,and excellent photothermal effects leading to superior in vitro antimicrobial activity.In addition,the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated.Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel.Wound closure,collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing.In summary,the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.

Enhanced burn wound healing by controlled-release 3D ADMSC-derived exosome-loaded hyaluronan hydrogel

Adipose mesenchymal stem cell(ADMSC)-derived exosomes(ADMSC-Exos)have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns.However,the low yield,easy loss after direct coating,and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing.And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques,especially in exosome-releasing hydrogel system.Therefore,we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing,namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid(HA).In this project,we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional(2D)plate culture(2D-Exos),microcarrier culture(2.5D-Exos),and 3D-printed microfiber culture(3D-Exos).Results showed that compared with 2D-Exos and 2.5D-Exos,3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly.Additionally,3D-Exos had stronger angiogenesis-promoting effects in tube formation of(HUVECs)cells.Moreover,we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos,including accelerated burn wound healing rate and better collagen remodeling.The study findings reveal that the HA-loaded,controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing,while concurrently introducing a facile application approach.This system markedly bolsters the exosomal loading efficiency,provides a robust protective milieu,and potentiates the inherent biological functionalities of the exosomes.Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future,and a novel strategy for healing severe burns.