Adipose Mesenchymal Stem Cell Derived Exosomes Promote Keratinocytes and Fibroblasts Embedded in Collagen/Platelet‐Rich Plasma Scaffold and Accelerate Wound Healing

Abstract

Engineered skin substitutes derived from human skin significantly reduce inflammatory reactions mediated by foreign/artificial materials and are consequently easier to use for clinical application. Type I collagen is a main component of the extracellular matrix during wound healing and has excellent biocompatibility, and platelet‐rich plasma can be used as the initiator of the healing cascade. Adipose mesenchymal stem cell derived exosomes are crucial for tissue repair and play key roles in enhancing cell regeneration, promoting angiogenesis, regulating inflammation, and remodeling extracellular matrix. Herein, Type I collagen and platelet‐rich plasma, which provide natural supports for keratinocyte and fibroblast adhesion, migration, and proliferation, are mixed to form a stable 3D scaffold. Adipose mesenchymal stem cell derived exosomes are added to the scaffold to improve the performance of the engineered skin. The physicochemical properties of this cellular scaffold are analyzed, and the repair effect is evaluated in a full‐thickness skin defect mouse model. The cellular scaffold reduces the level of inflammation and promotes cell proliferation and angiogenesis to accelerate wound healing. Proteomic analysis shows that exosomes exhibit excellent anti‐inflammatory and proangiogenic effects in collagen/platelet‐rich plasma scaffolds. The proposed method provides a new therapeutic strategy and theoretical basis for tissue regeneration and wound repair.

Plasma-Based Scaffold Containing Bone-Marrow Mononuclear Cells Promotes Wound Healing in a Mouse Model of Pressure Injury

“…In general terms, it was observed here that treatment with Plasma + BM-MNC accelerated wound healing. This result is in line with the findings of several research groups using a scaffold alone or in combination with cells 10 or even exosomes, such as recently reported by Wang et al 28 . These authors used a collagen/platelet-rich plasma scaffold containing adipocyte-derived exosomes and detected faster wound healing than without treatment.…”

Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy

“…Notable advancements in tissue regeneration encompassing the skin, bone, cartilage, nerves, and tendons have demonstrated the system's efficacy ( Table 5 ). For instance, for skin regeneration, the exosomes could promote cell proliferation and angiogenesis and accelerate the healing [ 175 , 228 , 229 ]. For bone and cartilage regeneration, such systems could facilitate tissue repair by providing osteogenic and chondrogenic factors [ 230 ].…”

“… Regulation of fibroblast proliferation and differentiation: Fibroblasts, as the primary cellular component of loose connective tissue, originate from mesenchymal cells during embryonic development and play pivotal roles in hair follicle initiation and scar formation during wound healing [ 239 ]. ADSC-Exos can boost the proliferation capacity of fibroblasts in vitro and within the wound area, increasing the expression of ki67 [ 228 ]. Additionally, they may increase the mRNA levels of genes encoding α-smooth muscle actin (α-SMA) and fibroblast growth factor-2 (FGF-2) [ 240 ].…”

Engineered exosomes and composite biomaterials for tissue regeneration

“…Exosomal functions have been extensively studied, and the possibility of controlling tissue repair and regeneration is becoming increasingly important; for example, exosomes could be an attractive alternative to numerous cell and tissue engineering techniques 28 . For instance, several investigations of mesenchymal stem cell (MSC) transplantation for tissue regeneration have shown that MSCs primarily alter cells through paracrine signaling mediated by the exosomes they release 29 , 30 . Thus, a cell-free approach that uses paracrine agents, such as exosomes, to encourage tissue repair and regeneration would avoid the potential risks of direct stem cell transplantation, including teratomas, immunological rejection, and the decreased capacity of the engrafted cells to mediate tissue regeneration 31 , 32 .…”