3D printed ordered porous CSMA/GelMA hydrogel scaffold regulates ADSC repair function, providing new material ideas for diabetes wound treatment

Research background and material design

Chronic diabetes wounds are in a microenvironment that is not conducive to cell survival for a long time, and the survival rate and repair activity of transplanted stem cells are often limited. To solve this problem, researchers have constructed a 3D printing ordered porous hydrogel scaffold platform with controllable structure. The material system is a composite photocrosslinking system of chitosan methacrylate (CSMA) and gelatin methacryloyl (GelMA). The study aims to verify whether the topological ordering of the scaffold can serve as a biomaterial clue to regulate the function of adipose derived mesenchymal stem cells (ADSCs). To highlight the influence of topological structure itself, the research team used the same photo crosslinked CSMA/GelMA precursor system and employed the same crosslinking and freeze-drying rehydration process to prepare two types of scaffolds, ordered and disordered, with only different spatial pore structures. Among the various ordered structures tested, the scaffold with a pore size of 200 μ m exhibited the most favorable early biological performance and was therefore selected for subsequent research.

The effect of topological structure on ADSC behavior and signaling pathways

Experimental results show that ordered topological structure can induce ADSC polarization, directional F-actin organization, and nuclear elongation and arrangement, indicating that the cytoskeleton and nucleus undergo coordinated remodeling.

. At the mechanistic level, ordered scaffolds increased FAK phosphorylation levels and enhanced YAP nuclear localization. When drugs are used to inhibit FAK, the YAP related response and the reparative paracrine advantage brought by ordered topology are weakened, indicating that the FAK-YAP related mechanical transduction pathway plays a key role in this process. On this basis, continuous delivery of SDF-1 α further enhances the reparative secretion profile, at least partially through CXCR4-AKT/ERK related signaling. This result suggests that in the design of medical polymer scaffolds, in addition to pore structure topology clues, the sustained presentation of bioactive factors can also serve as a strategy for synergistic regulation of stem cell function.

Repair effect in diabetes wound model

In the STZ induced full-thickness skin wound model of diabetes mice, the integrated orderly scaffold strategy improved wound closure, histological reconstruction, collagen deposition, and CD31 and CD206 related repair changes. When used in conjunction with ADSC, the benefits are most significant. These findings support the existence of the “topology – mechanical transduction – function” axis in the scaffold system, and provide a basis for biomaterial guided stem cell therapy for diabetes wound healing.

Inspiration for polymer additives and medical polymer industry

From the perspective of material processing and medical devices, this study demonstrates the processability of photo crosslinked natural polymer composite systems in 3D printed porous scaffolds.

. The CSMA/GelMA system forms a stable porous structure through photo crosslinking and freeze-drying rehydration process, and the topological parameters such as pore size can be designed and controlled during the printing process. This provides a reference path for the manufacturing of medical polymer disposable consumables, wound dressings, and tissue engineering scaffolds. For the polymer additive industry, the selection of photoinitiators, crosslinking agents, and stabilizers directly affects the crosslinking efficiency, printing accuracy, and mechanical and degradation behavior of CSMA/GelMA precursors, which in turn affects cell response. In addition, the durability and biocompatibility of stents in sterilization, storage, and clinical use are also important aspects that must be considered when transitioning such materials from the laboratory to medical products. The study did not involve specific additive formulations or commercial products, but its proposed topology mechanical transduction functional design logic provides new ideas for the integrated development of structural and functional properties of medical polymer materials.

Information source:3D‐Printed Ordered Porous CSMA/GelMA Hydrogel Scaffolds Enhance ADSC Reparative Function With FAK–YAP‐Related Mechanotransductive Changes， Organized by Herun Chemical.