Mesenchymal stem cells increase collagen infiltration and improve wound healing response to porous titanium percutaneous implants

Abstract

Epidermal downgrowth, commonly associated with long-term percutaneous implants, weakens the skin-implant seal and greatly increases the vulnerability of the site to infection. To improve the skin attachment and early tissue integration with porous metal percutaneous implants, we evaluated the effect of bone marrow-derived mesenchymal stem cells (BMMSCs) to provide wound healing cues and vascularization to the dermal and epidermal tissues in establishing a barrier with the implant. Two porous metal percutaneous implants, one treated with BMMSCs and one untreated, were placed subdermally on the dorsum of Lewis rats. Implants were evaluated at 0, 3, 7, 28, and 56 days after implantation. Histological analyses evaluated cellular infiltrates, vascularization, quantity and quality of tissue ingrowth, epidermal downgrowth, and fibrous encapsulation. The amount of collagen infiltrating the porous coating was significantly greater for the BMMSC-treated implants at 3 and 28 days post implantation compared to untreated implants. There was an early influx and resolution of cellular inflammatory infiltrates in the treated implants compared to the untreated, though not statistically significant. Vascularization increased over time in both treated and untreated implants, with no statistical significance. Epidermal downgrowth was minimally observed in all implants with or without the BMMSC treatment. Our results suggest that BMMSCs can influence an early and rapid resolution of acute and chronic inflammation in wound healing, and can stimulate early collagen deposition and granulation tissue associated with later stages of wound repair. These findings provide evidence that BMMSCs can stimulate a more rapid and improved barrier between the skin and porous metal percutaneous implant.

Effect of Bone Marrow Derived Mesenchymal Stem Cells on Healing of Induced Full-Thickness Skin Wounds in Albino Rat

“…This gross observation was further supported by the histopathological findings of early deposition of relatively wider granulation tissue with more cellularity in BMSCstreated wounds after 1 week compared with non treated wounds. These results were in agreement with earlier studies (21,25,26) and might be related to the role of BMSCs in the acceleration of granulation tissue formation that is extremely resistant to infection, provides a surface over which epithelium is able to migrate and contains fibroblasts that produce collagen for wound healing (24). In this study, histopathological evaluation of wound from BMSCs-treated groups after 1 week revealed early development of crust, evident inflammatory infiltrate, wider and more cellular granulation tissue, evident neovascularisation, earlier deposition of newly formed collagen and enchroachement of adjacent epidermis over wound edges than in non treated wounds.…”

“…The healed dermis showed persistence of inflammation, numerous blood vessels, many fibroblasts, thick parallel poorly organized collagen fibres indicating healing with scar formation. The previous findings were in agreement with other studies (3,21,26).…”

“…After three weeks, it became thicker and was arranged in different directions in a network like manner that mimic control skin. These findings might be attributed to the initial deposition of thin collagen fibrils (type III) that were later resorbed and replaced with thicker fibrils (type I) aligned with stress lines indicating maturity of wound (22,25,26). Eventually, in delayed healing of wounds in systemically treated group after three weeks, collagen fibres were still relatively thin and oriented parallel to the skin indicating delayed healing.…”

“…These findings might be attributed to the role of BMSCs in neovascularisation to sustain the newly formed granulation tissue (8,24,26). BMSCs could differentiate into endothelial cells and pericytes (27).…”

Porous Titanium Implants: A Review

“…[181] In another study, a nano zeolitic imidazolate-framework produced by the hydrothermal method enhanced ALP activity, promoted extracellular matrix mineralization, and up-regulated osteogenic potential in MG63 cells and inhibited growth of Streptococcus mutans. [182,183] The results cited above suggest that given a certain porosity, one can decrease the likelihood of infection, even without an antibacterial additive to the implant surface. [181] Isackson et al, in their works, evaluated porous titanium percutaneous implants for orthopedic purposes.…”