Effect of mechanical stimulation on bone marrow stromal cell–seeded tendon slice constructs: A potential engineered tendon patch for rotator cuff repair

Abstract

Cell-based tissue engineered tendons have potential to improve clinical outcomes following rotator cuff repair, especially in large or massive rotator cuff tears, which pose a great clinical challenge. The aim of this study was to develop a method of constructing a functional engineered tendon patch for rotator cuff repair with cyclic mechanical stimulation. Decellularized tendon slices (DTSs) were seeded with BMSCs and subjected to cyclic stretching for 1, 3, or 7 days. The mechanical properties, morphologic characteristics and tendon-related gene expression of the constructs were investigated. Viable BMSCs were observed on the DTS after 7 days. BMSCs penetrated into the DTSs and formed dense cell sheets after 7 days of mechanical stretching. Gene expression of type I collagen, decorin, and tenomodulin significantly increased in cyclically stretched BMSC-DTS constructs compared with the unstrained control group (P < 0.05). The ultimate tensile strength and stiffness of the cyclically stretched tendon constructs were similar to the unstrained control group (P > 0.05). In conclusion, mechanical stimulation of BMSC-DTS constructs upregulated expression of tendon-related proteins, promoted cell tenogenic differentiation, facilitated cell infiltration and formation of cell sheets, and retained mechanical properties. The patch could be used as a graft to enhance the surgical repair of rotator cuff tears.

Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation

“…COL1 is the most abundant tendon ECM protein, which is crucial for repair and regeneration of the fibrous tissues. In other studies, mechanical stimulation was also demonstrated to promote the COL1 protein production in tenocytes [80], dermal fibroblasts [81], MSC [82], and tendon derived stem cells [48]. The changes in gene expression on our dynamically cultured HADMSC/HT/HUVEC-woven fabric constructs were similar to those studies which evaluated the effect of tensile strain on MSC seeded silk fibers [83], MSC-seeded poly(lactide-co-glycolide) nanofiber meshes [77], and tendon derived stem cells seeded poly(L-lactide-co-e-caprolactone)/collagen scaffolds [49], reporting a similar upregulation of SCX and TNC, as well as COL1 and COL3.…”

The revitalisation of flexor tendon allografts with bone marrow stromal cells and mechanical stimulation

“…Their results showed that intermittent cyclic strain can increase cell proliferation, promote COL1 production, and maintain tenocyte morphologic characteristics in vitro . 16 Qin et al 22 also reported that mechanical stimulation of decellularised tendon slices seeded with BMSCs (BMSCs-DTSs) increased the expression of tendon-related genes (COL1, decorin, and tenomodulin) after seven days in culture. Our findings were consistent with these previous studies and provide additional evidence to support the benefit of mechanical stimulation of cell-based constructs before implantation.…”

“…20 MMP13 expression is an important marker of matrix degradation and remodeling in tendon tissue, and is regulated in both loading and unloading conditions. 21 Qin et al reported 22 that expression of MMP13 in tenocytes with mechanical loading in an in vivo model was decreased. However, by blocking Interleukin (IL)-1 beta, the MMP13 expression was increased, which suggested MMP13 is regulated by both IL-1beta-dependent, and IL-1beta-independent pathways.…”

“…In addition, MMP13 has been shown to have substrate specificity for a range of matrix components, such as MMP2 and MMP9. 22 …”

The extracellular microscape governs mesenchymal stem cell fate

“…MSC enhancement of potential tendon and ligament grafts has centred on cyclical tension of a collagen scaffold either artificially produced or decellularized from a donor site, then re-impregnated with MSCs to promote fibroblastic differentiation [94, 95]. This type of loading elicited uniaxial alignment of MSCs on synthetic yarns and promoted the production of collagen I [96], and a 3 % strain induced tendon-like gene expression profiles in MSCs seeded on these scaffolds [97].…”