The construction and maintenance of an appropriate regenerative microenvironment during the repair of tissue and organs have always been a challenge in treatment. Mesenchymal stem cells (MSCs) have been widely used for local implantation to regulate the microenvironment due to their multi-directional differentiation, immune regulation, and paracrine effects. However, existing systems mostly rely on physical adsorption and have weak interactions and poor integration, resulting in a decline in the activity of MSCs after implantation, low retention efficiency, and prone to migration and apoptosis, severely restricting the therapeutic efficacy and becoming the core bottleneck for the clinical translation of this strategy.
Facing this challenge, Professor Yang Yumin from Nantong University, Researcher Zhang Luchong from Nanjing University of Chinese Medicine, and Professor Liu Xin from the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University of Chinese Medicine proposed a new strategy for peripheral nerve injury, especially for long-distance nerve defects due to their complex structure and the special nature of the regenerative microenvironment. They published the research results titled "A Bio-Orthogonal Engineered Chitosan Platform for Enhanced Mesenchymal Stem Cells Delivery and Function in Peripheral Nerve Repair" in Advanced Materials. This study successfully constructed a bio-orthogonal engineered chitosan platform system based on MSCs and chitosan materials. Through covalent binding between MSCs and chitosan materials, this system significantly enhanced the cell survival rate, retention ability at the implant site, and cytokine secretion function of MSCs. When applied to peripheral nerve injury models, it can effectively regulate the early regenerative microenvironment of the injury, accelerate the process of nerve regeneration, and show significant therapeutic advantages in the repair of long-distance nerve defects.
Key analysis
This study achieved rapid and efficient covalent binding of MSCs and chitosan materials through a bio-orthogonal reaction under mild conditions. The research results show that compared with the previous non-covalent binding connection methods between MSCs and materials, covalent binding can not only effectively enhance the retention of MSCs on chitosan materials but also promote the survival of MSCs by activating the PI3K/AKT signaling pathway, and simultaneously upregulate the secretion of key factors that positively regulate nerve regeneration such as hepatocyte growth factor (HGF), axon guidance molecule (Slit3), and cell communication network factor 1 (CCN1), effectively promoting nerve growth and Schwann cell migration. In peripheral nerve injury models, this system can synergistically promote nerve repair by regulating the early immune microenvironment, accelerating Wallerian degeneration, remodeling the extracellular matrix, and promoting angiogenesis, especially showing remarkable therapeutic effects in long-distance nerve defects (Figure 1).
This work not only achieved efficient repair of peripheral nerve injuries but also proposed a covalent binding strategy of stem cells and biomaterials, promoting cell retention while improving the survival and function of MSCs. This strategy breaks through the limitation of low in situ retention efficiency of traditional stem cell therapy and can effectively enhance the repair effect of MSCs in peripheral nerves. More importantly, this strategy is simple, efficient, and easy to translate, and is expected to promote the clinical application of chitosan-MSC composite materials in regenerative medicine.
DOI: https://doi.org/10.1002/adma.202523237