A novel cell-containing device for regenerative medicine: biodegradable nonwoven filters with peripheral blood cells promote wound healing

Abstract

The efficacy of skin regeneration devices consisting of nonwoven filters and peripheral blood cells was investigated for wound healing. We previously found that human peripheral blood cells enhanced their production of growth factors, such as transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor, when they were captured on nonwoven filters. Cells on biodegradable filters were expected to serve as a local supply of growth factors and cell sources when they were placed in wounded skin. Nonwoven filters made of biodegradable polylactic acid (PLA) were cut out as 13-mm disks and placed into cell-capturing devices. Mouse peripheral blood was filtered, resulting in PLA filters with mouse peripheral blood cells (m-PBCs) at capture rates of 65.8 ± 5.2%. Then, the filters were attached to full-thickness surgical wounds in a diabetic db/db mouse skin for 14 days as a model of severe chronic wounds. The wound area treated with PLA nonwoven filters with m-PBCs (PLA/B+) was reduced to 8.5 ± 12.2% when compared with day 0, although the non-treated control wounds showed reduction only to 60.6 ± 27.8%. However, the PLA filters without m-PBCs increased the wound area to 162.9 ± 118.7%. By histopathological study, the PLA/B+ groups more effectively accelerated formation of epithelium. The m-PBCs captured on the PLA filters enhanced keratinocyte growth factor (FGF-7) and TGF-β1 productions in vitro, which may be related to wound healing. This device is useful for regeneration of wounded skin and may be adaptable for another application.

Effects of Mesenchymal Stem Cell‐Derived Paracrine Signals and Their Delivery Strategies

“…[ 43–46 ] These findings not only highlight the importance to better characterize the secretome for quality control purpose, but also reveal the need to understand the optimal secretome profile for a specific application and identify the specific mechanistic pathways in regeneration of different tissue types. For example, the secretome of MSCs during cartilage regeneration or chondrogenesis is characterized by high levels of TGF‐ β 1, tissue inhibitor of metalloproteinase 3 (TIMP‐3), and matrix metalloproteinase 13 (MMP13) [ 35,47–51 ] Among the secretome components, fibroblast growth factor‐1 (FGF‐1) and PDGF, besides their angiogenic properties, also contribute to the proliferation of chondrocytes. [ 52 ] The miRNA components miR‐204, miR‐211, miR‐337 are correlated with preventing cartilage degradation and promoting chondrogenesis.…”

Pre-clinical Research of Human Amnion-derived Mesenchymal Stem Cells and its First Clinical Treatment for a Severe Uremic Calciphylaxis Patient

“…FGF-7 can contribute to synthesize various proangiogenic molecules, including VEGF, to promote angiogenesis (Qu et al, 2018). As keratinocyte growth factor, FGF-7 is upregulated after skin injury, stimulates the proliferation (Kao et al, 2011) and migration (Qu et al, 2018) of keratinocytes and accelerates wound healing by reepithelialization (Iwamoto et al, 2015). FGF7 is important for the formation of hair follicles (Qu et al, 2018).…”

Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects

“…As one of the main components of the epithelium is keratinocytes, FGF-7 accelerates the proliferation of keratinocyte. The formation of granulation tissue, the promotion of angiogenesis and epithelization are important treatment methods for chronic wound healing ( 101 ). In addition, new research shows that cells obtained in dermal connective tissue can be used as mesenchymal stem cells, because the reduction and delay of FGF-7 growth factor production in diabetic patients improves with the improvement of this cell transplantation, and contribute to wound healing ( 102 ).…”