Abstract
Cell-derived matrix (CDM) has proven its therapeutic potential and been utilized as a promising resource in tissue regeneration. In this study, we prepared a human fibroblast-derived matrix (FDM) by decellularization of in vitro cultured cells and transformed the FDM into a nano-sized suspended formulation (sFDM) using ultrasonication. The sFDM was then homogeneously mixed with Pluronic F127 and hyaluronic acid (HA), to effectively administer sFDM into target sites. Both sFDM and sFDM containing hydrogel (PH/sFDM) were characterized via immunofluorescence, sol–gel transition, rheological analysis, and biochemical factors array. We found that PH/sFDM hydrogel has biocompatible, mechanically stable, injectable properties and can be easily administered into the external and internal target regions. sFDM itself holds diverse bioactive molecules. Interestingly, sFDM-containing serum-free media helped maintain the metabolic activity of endothelial cells significantly better than those in serum-free condition. PH/sFDM also promoted vascular endothelial growth factor (VEGF) secretion from monocytes in vitro. Moreover, when we evaluated therapeutic effects of PH/sFDM via the murine full-thickness skin wound model, regenerative potential of PH/sFDM was supported by epidermal thickness, significantly more neovessel formation, and enhanced mature collagen deposition. The hindlimb ischemia model also found some therapeutic improvements, as assessed by accelerated blood reperfusion and substantially diminished necrosis and fibrosis in the gastrocnemius and tibialis muscles. Together, based on sFDM holding a strong therapeutic potential, our engineered hydrogel (PH/sFDM) should be a promising candidate in tissue engineering and regenerative medicine.
Highlights
Blood supply is a crucial event in the body to transport oxygen, nutrients, and cells for maintaining normal function of tissues and organs
We have documented the biomimetic characteristics of cell-derived Extracellular matrix (ECM) (CDM) in terms of compositional diversity of natural ECM and bioactive growth factors/cytokines embedded in the CDM [9,10]
Once human fibroblast-derived matrix (FDM) was prepared by the decellularization process, the representative ECM proteins in the FDM were found richly and evenly distributed via immunofluorescence (Figure 1A)
Summary
Blood supply is a crucial event in the body to transport oxygen, nutrients, and cells for maintaining normal function of tissues and organs. Since insufficient blood supply is a major cause of several chronic diseases, numerous studies have concentrated on the technologies for advanced angiogenesis by using various strategies, such as scaffolds, hydrogels, cells, growth factors, and/or chemokines [3,4,5]. Due to its intrinsically biomimetic properties, decellularized ECM has been an attractive resource in tissue engineering that is mainly obtained from tissues, organs or even cells via decellularization processes [8]. Our previous studies demonstrated that CDM possesses a considerable capability of promoting angiogenesis in vitro and in vivo by providing a unique microenvironment for angiogenic cellular functions [11,12]. To deliver sensitive biomolecules (growth factors, proteins, and exosomes), many research groups have combined them with biocompatible hydrogels [13,14,15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
