Programmable DNA Hydrogel Provides Suitable Microenvironment for Enhancing TSPCS Therapy in Healing of Tendinopathy

Abstract

Tendon stem/progenitor cells (TSPCs) therapy is a promising strategy for enhancing cell matrix and collagen synthesis, and regulating the metabolism of the tendon microenvironment during tendon injury repair. Nevertheless, the barren microenvironment and gliding shear of tendon cause insufficient nutrition supply, damage, and aggregation of injected TSPCs around tendon tissues, which severely hinders their clinical application in tendinopathy. In this study, a TSPCs delivery system is developed by encapsulating TSPCs within a DNA hydrogel (TSPCs‐Gel) as the DNA hydrogel offers an excellent artificial extracellular matrix (ECM) microenvironment by providing nutrition for proliferation and protection against shear forces. This delivery method restricts TSPCs to the tendons, significantly extending their retention time. It is also found that TSPCs‐Gel injections can promote the healing of rat tendinopathy in vivo, where cross‐sectional area and load to failure of injured tendons in rats are significantly improved compared to the free TSPCs treatment group at 8 weeks. Furthermore, the potential healing mechanism of TSPCs‐Gel is investigated by RNA‐sequencing to identify a series of potential gene and signaling pathway targets for further clinical treatment strategies. These findings suggest the potential pathways of using DNA hydrogels as artificial ECMs to promote cell proliferation and protect TSPCs in TSPC therapy.

Global research trends and hotspots on tendon-derived stem cell: a bibliometric visualization study

“…To address this issue, Guanglin Wang et al developed a DNA hydrogel scaffold encapsulating TDSCs. This DNA hydrogel scaffold extends the retention time of TDSCs on the tendon, providing an artificial microenvironment conducive to better nutrition, thereby promoting tendon injury repair ( Ge et al, 2023 ).…”

The Functions and Mechanisms of Tendon Stem/Progenitor Cells in Tendon Healing

“…Third, to create a suitable niche for the tendon lineage differentiation of TSPCs, such as ECM combined with hydrogel to promote the sustained generation of TSPCs. Ge et al [ 136 ] injected TSPCs-Gel into rat injured Achilles tendons using DNA hydrogel as an excellent artificial ECM for proliferation and protection of TSPCs (TSPCs-Gel). They found that TSPCs-Gel injection not only promoted the healing of rat tendon, but also improved its ultimate loading ability.…”

Hydrogels in the Treatment of Degenerative Tendinopathy

“…Delivery system for tendon stem/progenitor cells Hydrogel promotes cell proliferation and protection [12] 3D printed hydrogel particles containing PRP Tendon postinjury repair Hydrogel promotes tendon differentiation in tendon-derived stem cell and reduces inflammatory response [16] Gelatin/Fe3O4/Celecoxib hydrogel Repair the later stage in tendinopathy Hydrogel reduced inflammatory reaction of macrophage response [19] Chitosan-collagen HG with poly-L-lactide fibers To mimic the glycosaminoglycans of sheath extracellular matrix for tendon regeneration Good cell proliferation was observed, tenocytes showed proper attachment and spreading on the scaffolds, indicating that they would be suitable for flexor tendon regeneration [38] Collagen I hydrogels Bioengineered Tissue microenvironments Scaffolds for engineered tissues with a diffusion capacity [43] Thermo-responsive in-situ HG based on poly (Nisopropylacrylamide)…”