Mesenchymal stem cell (MSC)-based approaches can be broadly divided into two categories: cell therapy and regenerative medicine. Cell therapy is focused on the anti-inflammatory, immune-regulatory, and homeostasis-regulatory actions of MSCs to treat disorders like malignant lymphoma, angina pectoris, and atopic dermatitis. Conversely, regenerative medicine is focused on MSCs playing a tissue engineering role, to enhance tissue regeneration using growth factors and scaffolds; for example, to generate tissue-engineered skin or cartilage, which have been assessed in clinical trials.

Our previous study showed that systemically injected MSCs improved attachment of the peri-implant epithelium (PIE) to the titanium (Ti) implant surface and accelerated tissue healing around the implant. Because the systemically injected MSCs accumulated around the experimental implant, we believe they acted through both regenerative medicine and cell therapy modes [1]. Indeed, the peri-implant tissue is always exposed to the possibility of inflammation because the Ti implant penetrates through the oral mucosa. However, many studies have shown that the PIE has a low sealing ability within the oral environment [2,3,4], meaning bacteria can more readily accumulate around the implant and induce inflammatory destruction more easily than around the natural tooth [5, 6]. Additionally, it is important to prevent epithelial down-growth by promoting epithelial cell adherence and stabilizing the epithelial soft tissue seal [7]. Therefore, improving local defense within the mucosa is indispensable to enabling successful implantation.

Some studies report that epithelial healing after implant replacement is similar to mucosa wound healing [8]. Wound healing goes through a genetically programmed repair process involving inflammation, cell proliferation, re-epithelialization, formation of granulation tissue, angiogenesis, interactions between various cell types, and matrix/tissue remodeling [9]. Therefore, the aim of MSC treatment is to regulate many cells to restore the structure, function, and physiology of damaged tissues around the implant [10].

Accumulation of MSCs adjacent to the damaged tissue following their administration into an implant model can be determined following “systemic” or “local” transplantation. Although systemic MSC administration has proven efficacious and has a large advantage as our above previous studies [11, 12], possible risks, including pulmonary embolism, pose a serious issue [13, 14]. It is therefore important to provide an alternative low-risk method that avoids MSCs becoming trapped within healthy organs. Despite this, cell regulation following local cell administration is not well-documented with respect to peri-implant tissue regeneration.