Control the fate of human umbilical cord mesenchymal stem cells with dual‐enzymatically cross‐linked gelatin hydrogels for potential applications in nerve regeneration

Abstract

Stem‐cell‐based therapy is a promising strategy to treat challenging neurological diseases, while its application is hindered primarily by the low viability and uncontrolled differentiation of stem cell. Hydrogel can be properly engineered to share similar characteristics with the target tissue, thus promoting cell viability and directing cell differentiation. In this study, we proposed a new dual‐enzymatically cross‐linked and injectable gelatin hydrogel for regulating survival, proliferation, and differentiation of human umbilical cord mesenchymal stem cells (hUC‐MSCs) in a three‐dimensional matrix. This injectable gelatin hydrogel was formed by oxidative coupling of gelatin–hydroxyphenyl acid conjugates catalyzed by hydrogen horseradish peroxidase (HRP) and choline oxidase (ChOx). Modulus and H2O2 release can be well controlled by ChOx activity. Results from calcein‐AM/PI staining and Ki67 immunofluorescence tests demonstrated that the survival and proliferation behavior of hUC‐MSCs were highly enhanced in HRP1UChOx0.25U hydrogel with lower modulus and less H2O2 release compared with other groups. Attractively, the expression of neuron‐specific markers β‐III tubulin, neurofilament light chain (NFL), and synapsin‐1 was significantly increased in HRP1UChOx0.25U hydrogel as well. Additionally, in vitro hemolysis test and in vivo HE staining data highlighted the good biocompatibility. Undoubtedly, this injectable gelatin hydrogel's ability to control hUC‐MSCs' fate holds enormous potentials in nervous disorders' therapy and nerve regeneration.

Injectable and Antioxidative HT/QGA Hydrogel for Potential Application in Wound Healing

“…The hemolysis ratio is the most simple and effective method to measure the blood compatibility of hydrogels. According to the assessment criteria of the International Organization for Standardization (ISO) 10993-4, hydrogels are safe and can be applied to clinical use under the condition of a hemolysis ratio lower than 5% [ 30 ]. As shown in Figure 6 c,d, the extraction of hydrogels was as clear as that of the normal saline group, and the hemolysis ratio of the HT 1 /QGA 0 , HT 1 /QGA 0.1 , HT 1 /QGA 0.3 , and HT 1 /QGA 0.5 hydrogels were 0.27 ± 0.09%, 0.22 ± 0.03%, 0.39 ± 0.04%, and 0.58 ± 0.14%, respectively.…”

A Review of Patents and Innovative Biopolymer-Based Hydrogels

“…Gelatin-based hydrogels are non-immunogenic, non-toxic and water-soluble materials. Because of their exceptional biocompatibility and biodegradability in physiological conditions, they were employed for various biomedical uses, such as for cell encapsulation, wound healing [81,82], skin substitute [83], regeneration of nerve [84], reconstruction of soft tissue [85], bone repair [86] and 3D bioprinting [87]. An interesting study was presented wherein cell-cultured artificial meat was obtained using bovine satellite muscle-derived cells cultivated in vitro, which were capable of growing and connecting to a porous naturally occurring gelatin (GL)-based hydrogel enriched by proanthocyanidins (PC) from grape seed extract (GL-PC) (Figure 3a) [88].…”

One‐Step Synthesis of Multifunctional Chitosan Hydrogel for Full‐Thickness Wound Closure and Healing

“…The storage modulus usually functions as an indicator of the stiffness of a given viscoelastic material. [56] The linear viscoelastic behavior of the hydrogels was characterized by oscillation frequency sweep measurement, and the results were presented in Figure S2b, Supporting Information. At an angular frequency of 100 rad s −1 , the storage modulus of Fe 0 , Fe 2.25 , Fe 4.5 , and Fe 9 hydrogel is 142, 84, 129, and 125 Pa, respectively.…”