Platelet-rich plasma (PRP) is the portion of plasma with a platelet concentration above baseline that is recovered through centrifugation of autologous blood. PRP therapy is currently used for wound healing and pain relief in diverse medical fields. Although there have been recent reports of adverse events (AEs) possibly related to PRP treatment, the safety profile of PRP treatment remains unclear. Therefore, this review discusses the risks inherent in PRP therapy and the current issues by surveying reports on AEs associated with PRP treatment within different fields.

Low-level laser therapy (LLLT) with various types of lasers promotes fibroblast proliferation and migration during the process of wound healing. Although LLLT with a carbon dioxide (CO₂) laser was also reported to promote wound healing, the underlying mechanisms at the cellular level have not been previously described. Herein, we investigated the effect of LLLT with a CO₂ laser on fibroblast proliferation and migration. Cultured human dermal fibroblasts were prepared. MTS and cell migration assays were performed with fibroblasts after LLLT with a CO₂ laser at various doses (0.1, 0.5, 1.0, 2.0, or 5.0 J/cm²) to observe the effects of LLLT with a CO₂ laser on the proliferation and migration of fibroblasts. The non-irradiated group served as the control. Moreover, western blot analysis was performed using fibroblasts after LLLT with a CO₂ laser to analyze changes in the activities of Akt, extracellular signal-regulated kinase (ERK), and Jun N-terminal kinase (JNK), which are signaling molecules associated with cell proliferation and migration. Finally, the MTS assay, a cell migration assay, and western blot analysis were performed using fibroblasts treated with inhibitors of Akt, ERK, or JNK before LLLT with a CO₂ laser. In MTS and cell migration assays, fibroblast proliferation and migration were promoted after LLLT with a CO₂ laser at 1.0 J/cm². Western blot analysis revealed that Akt, ERK, and JNK activities were promoted in fibroblasts after LLLT with a CO₂ laser at 1.0 J/cm². Moreover, inhibition of Akt, ERK, or JNK significantly blocked fibroblast proliferation and migration. These findings suggested that LLLT with a CO₂ laser would accelerate wound healing by promoting the proliferation and migration of fibroblasts. Activation of Akt, ERK, and JNK was essential for CO₂ laser-induced proliferation and migration of fibroblasts.

The oral cavity is a unique environment that consists of teeth surrounded by periodontal tissues, oral mucosae with minor salivary glands, and terminal parts of major salivary glands that open into the oral cavity. The cavity is constantly exposed to viral and microbial pathogens. Recent studies indicate that components of the plasminogen (Plg)/plasmin (Pm) system are expressed in tissues of the oral cavity, such as the salivary gland, and contribute to microbial infection and inflammation, such as periodontitis. The Plg/Pm system fulfills two major functions: (a) the destruction of fibrin deposits in the bloodstream or damaged tissues, a process called fibrinolysis, and (b) non-fibrinolytic actions that include the proteolytic modulation of proteins. One can observe both functions during inflammation. The virus that causes the coronavirus disease 2019 (COVID-19) exploits the fibrinolytic and non-fibrinolytic functions of the Plg/Pm system in the oral cavity. During COVID-19, well-established coagulopathy with the development of microthrombi requires constant activation of the fibrinolytic function. Furthermore, viral entry is modulated by receptors such as TMPRSS2, which is necessary in the oral cavity, leading to a derailed immune response that peaks in cytokine storm syndrome. This paper outlines the significance of the Plg/Pm system for infectious and inflammatory diseases that start in the oral cavity.

Morikuni Tobita, DDS, PhD/Hiroshi Mizuno, MD, PhD: Innovative developments in the multidisciplinary field of tissue engineering have yielded various implementation strategies and the possibility of functional tissue regeneration. Technologic advances in the combination of stem cells, biomaterials, and growth factors have created unique opportunities to fabricate tissues in vivo and in vitro. The therapeutic potential of human multipotent mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose tissue, has generated increasing interest in a wide variety of biomedical disciplines. These cells can differentiate into a variety of tissue types, including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have some advantages compared with other sources of stem cells, most notably that a large number of cells can be easily and quickly isolated from adipose tissue. In current clinical therapy for periodontal tissue regeneration, several methods have been developed and applied either alone or in combination, such as enamel matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic bone grafts, and growth factors. However, there are various limitations and shortcomings for periodontal tissue regeneration using current methods. Recently, periodontal tissue regeneration using MSCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because the various secreted growth factors from MSCs might not only promote the regeneration of periodontal tissue but also encourage neovascularization of the damaged tissues. Adipose-derived stem cells are especially effective for neovascularization compared with other MSC sources. In this review, the possibility and potential of adipose-derived stem cells for regenerative medicine are introduced. Of particular interest, periodontal tissue regeneration with adipose-derived stem cells is discussed.

Adipose-derived stem cells (ASCs) secrete various growth factors to promote wound healing and to regenerate various tissues, such as bone, cartilage, and fat tissue. Subcutaneous adipose tissue is a considerable cell source in clinical practice and can be collected relatively easily and safely under local anesthesia. Moreover, platelet-rich plasma (PRP), a plasma component containing many platelets purified by centrifuging the collected blood, also promotes wound healing. PRP can be easily gelled and is therefore attracting attention as a scaffolding material for transplanted cells. The usefulness of a mixture of ASCs and PRP for periodontal tissue regeneration has been in vitro demonstrated in our previous study. The aim of this study is to present the protocol of translation of tissue regeneration with ASCs and PRP into practical use, evaluating its efficacy. This study is a multicenter, randomized, open-label comparative clinical trial. Fifteen patients will be randomly assigned to the treatment with mixture of ASCs and PRP or enamel matrix derivate administration into periodontal tissue defects. Increase in height of new alveolar bone in the transplanted area will be evaluated. The evaluation will be performed using dental radiographs after 36 weeks of transplantation. Occurrence of adverse events will be evaluated as secondary outcome. This clinical study was initiated after meeting the regulations to be complied with, including ethical review and regulatory notifications. If effective, this cell therapy using autologous mesenchymal stem cells can represent a useful medical technology for regeneration of periodontal defects.