The clinical use of bioactive molecules in bone regeneration has been known to have side effects, which result from uncontrolled and supraphysiological doses. In this study, we demonstrated the synergistic effect of two bioactive molecules, bone morphogenic protein-2 (BMP-2) and alendronate (ALN), by releasing them in a sequential manner. Collagen-hydroxyapatite composite scaffolds functionalized using BMP-2 are loaded with biodegradable microspheres where ALN is encapsulated. The results indicate an initial release of BMP-2 for a few days, followed by the sequential release of ALN after two weeks. The composite scaffolds significantly increase osteogenic activity owing to the synergistic effect of BMP-2 and ALN. Enhanced bone regeneration was identified at eight weeks post-implantation in the rat 8-mm critical-sized defect. Our findings suggest that the sequential delivery of BMP-2 and ALN from the scaffolds results in a synergistic effect on bone regeneration, which is unprecedented. Therefore, such a system exhibits potential for the application of cell-free tissue engineering.

Background: Cell-assisted lipotransfer is a process in which fat grafting is supplemented with autologous adipose-derived stromal cells. Since the efficacy of the technique was demonstrated, studies have focused on the mechanism by which cell-assisted lipotransfer enhances the rate of graft survival. However, the microenvironmental changes in donor and recipient tissue associated with cell-assisted lipotransfer remain unclear. Methods: The authors introduced an animal model of cell-assisted lipotransfer using two different transgenic reporter mice. Donor fat from green fluorescent protein–expressing C57BL/6J mice and donor adipose-derived stromal cells from DsRed-expressing C57BL/6J mice were co-transplanted into recipient C57BL/6J mice. During adipose remodeling after cell-assisted lipotransfer, the fate of each donor adipocyte and donor adipose-derived stromal cell was traced using immunofluorescent staining with the whole-mount method. Results: Adipose-derived stromal cell supplementation altered inflammation and promoted angiogenesis and subsequent revascularization in recipient tissue. Tracing at postoperative week 4 revealed that surviving donor adipose-derived stromal cells participated in angiogenesis by differentiating into endothelial cells. Moreover, newly differentiated fat from donor adipose-derived stromal cells and recipient tissue integrated with surviving donor fat, leading to improved retention of the graft. Adipose-derived stromal cell supplementation resulted in a quantitative difference in angiogenesis and adipogenesis during adipose remodeling according to the concentration of adipose-derived stromal cells. Conclusions: The authors characterized the dynamic changes occurring in donor adipose-derived stromal cells and fat and recipient tissue by tracing these cellular components following cell-assisted lipotransfer. The authors’ findings highlight the therapeutic value of cell-assisted lipotransfer in tissue transplantation.

During the past decade, many studies using platelet-rich plasma (PRP) or adipose-derived stem cells (ASCs) have been conducted in various medical fields, from cardiovascular research to applications for corneal diseases. Nonetheless, there are several limitations of practical applications of PRP and ASCs. Most reports of PRP are anecdotal and few include controls to determine the specific role of PRP. There is little consensus regarding PRP production and characterization. Some have reported the development of an antibody to bovine thrombin, which was the initiator of platelet activation. In the case of ASCs, good manufacturing practices are needed for the production of clinical-grade human stem cells, and in vitro expansion of ASCs requires approval of the Korea Food and Drug Administration, such that considerable expense and time are required. Additionally, some have reported that ASCs could have a potential risk of transformation to malignant cells. Therefore, the authors tried to investigate the latest research on the efficacy and safety of PRP and ASCs and report on the current state and regulation of these stem cell-based therapies.

Background Hypertrophic scars and keloids are associated with abnormal levels of growth factors. Silicone gel sheets are effective in treating and preventing hypertrophic scars and keloids. There has been no report on the change in growth factors in the scar tissue following the use of silicone gel sheeting for scar prevention. A prospective controlled trial was performed to evaluate whether growth factors are altered by the application of a silicone gel sheet on a fresh surgical scar. Methods Four of seven enrolled patients completed the study. Transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) were investigated immunohistochemically in biopsies taken from five scars at 4 months following surgery. Results In both the epidermis and the dermis, the expression of TGF-β1 (P=0.042 and P=0.042) and PDGF (P=0.043 and P=0.042) was significantly lower in the case of silicone gel sheet-treated scars than in the case of untreated scars. The expression of bFGF in the dermis was significantly higher in the case of silicone gel sheet-treated scars than in the case of untreated scars (P=0.042), but in the epidermis, the expression of bFGF showed no significant difference between the groups (P=0.655). Conclusions The levels of TGF-β1, PDGF, and bFGF are altered by the silicone gel sheet treatment, which might be one of the mechanisms of action in scar prevention.

Background. Dermatofibrosarcoma protuberans (DFSP), a rare low-grade sarcoma of fibroblast origin, tends to extend in a finger-like fashion beyond macroscopic tumor margins. Therefore, incomplete removal and subsequent recurrence are common. This study aimed to determine the efficacy of wide local excision (WLE) for controlling local recurrence of DFSP.Methods. The medical records of 90 DFSP patients who received WLE at our hospital between June 1992 and January 2015 were retrospectively reviewed. WLE was conducted including a 3 cm (range, 1 to 5 cm) safety margin according to tumor size, location, and recurrence status. Clinical and tumor characteristics and surgical methods were evaluated for risk factor analysis and local recurrence-free survival.Results. DFSP occurred most often in patients in their 30s (30%) and on the trunk (51.1%). Five patients (5.5%) experienced local recurrence during the 43.4-month follow-up period. Recurrence was found at a mean of 10.8 months after WLE. Although no factors were significantly associated with recurrence, recurrences were more frequent in head and neck. Recurrence-free survival was 87% in 6 years and 77% in 7 years.Conclusions. WLE with adequate lateral and deep margins can effectively control local recurrence rate and is a simple and effective method to treat DFSP.

Although obesity is a newly considered risk factor for cancer, the mechanisms by which adipocyte-derived metabolites accelerate cancer malignancy have yet to be elucidated. To identify the connection among heterogeneous cell types, conventional methods including Transwell assays or conditioned media (CM) have been used; however, these methods do not fully reflect niche effects in the tumor microenvironment (TME). Here, we established an oxygen permeable polydimethylsiloxane (PDMS)-based three-dimensional (3D) culture system to allow direct attachment between human adipocyte derived stem cells (ADSCs) and cancer cells. By doing so, a physiologically bioactive TME was created, which could be used to reveal further the relationships between different cell types. We found that co-culture of cancer cells with ADSCs resulted in a dispersion phenomenon, and the dispersed spheroid was well matched with the enhanced metastatic potential of cancer cells. Lipid profiling and in vitro migration assays suggested that lipids are the driving force for cancer cell migration via HIF-1α upregulation. In addition, the lipid/HIF-1α axis promoted tumor metastasis in a xenograft mouse model. This study presents an in vitro model of a biomimetic TME and provides new mechanistic insights into the effects of ADSC-released fatty acids on cancer cells as oncometabolites.