Extracellular matrices derived from different cell sources and their effect on macrophage behavior and wound healing

Savitri, Cininta; Ha, Sang Su; Liao, Emily; Du, Pu

doi:10.1039/d0tb01885f

Cited by 29 publications

(38 citation statements)

References 44 publications

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“…However, some evidence of M1 macrophages were observed for dUA in mice and suggest that M1 macrophages are recruited to the inserted dUA although to a much lesser extent than M2 macrophages. This is in agreement with others [ 15 , 26 , 27 ], where for instance commercially available decellularised mesothelium heart valve products mainly exhibit M2 macrophages recellularisation upon subcutaneous implantation [ 15 ]. This stands in contrasts to decellularised porcine small intestinal specimens implanted in a rodent model of body wall repair, where similar numbers of M1 and M2 macrophages were found and which was consistent even after improving the decellularisation method [ 28 ].…”

Section: Discussionsupporting

confidence: 92%

Decellularised Human Umbilical Artery as a Vascular Graft Elicits Minimal Pro-Inflammatory Host Response Ex Vivo and In Vivo

Ahlmann

Fang

Mortensen

et al. 2021

IJMS

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Small diameter (<6 mm) vessel grafts still pose a challenge for scientists worldwide. Decellularised umbilical artery (dUA) remains promising as small diameter tissue engineered vascular graft (TEVG), yet their immunogenicity remains unknown. Herein, we evaluated the host immune responses, with a focus on the innate part, towards human dUA implantation in mice, and confirmed our findings in an ex vivo allogeneic human setup. Overall, we did not observe any differences in the number of circulating white blood cells nor the number of monocytes among three groups of mice (1) dUA patch; (2) Sham; and (3) Mock throughout the study (day −7 to 28). Likewise, we found no difference in systemic inflammatory and anti-inflammatory cytokine levels between groups. However, a massive local remodelling response with M2 macrophages were observed in the dUA at day 28, whereas M1 macrophages were less frequent. Moreover, human monocytes from allogeneic individuals were differentiated into macrophages and exposed to lyophilised dUA to maximize an eventual M1 response. Yet, dUA did not elicit any immediate M1 response as determined by the absence of CCR7 and CXCL10. Together this suggests that human dUA elicits a minimal pro-inflammatory response further supporting its use as a TEVG in an allogeneic setup.

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Section: Discussionsupporting

confidence: 92%

Decellularised Human Umbilical Artery as a Vascular Graft Elicits Minimal Pro-Inflammatory Host Response Ex Vivo and In Vivo

Ahlmann

Fang

Mortensen

et al. 2021

IJMS

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“…Therefore, we concentrated on three different hydrogel groups (PH, PH/FDM, and PH/sFDM). The defect only group repeatedly showed a poor wound healing in our previous work [26,32]. In addition, PH/sFDM treatment demonstrated enhanced blood reperfusion and a diminishing muscle (gastrocnemius and tibialis) necrosis in the hindlimb ischemic model (Figures 5 and 6).…”

Section: Discussionmentioning

confidence: 59%

“…As a delivery vehicle of sFDM, when Pluronic F127 was applied to skin wound, the hydrogel rapidly melted and flowed down. To overcome this problem, we tested HA and combined it with Pluronic F127 for reinforcing mechanical property of PH hydrogel, as previously reported [26]. HA also contribute to wound healing processes as reported in the matrix assembly and angiogenesis during tissue remodeling [27].…”

Section: Discussionmentioning

confidence: 99%

“…FDM can be obtained from different cell sources, such as lung fibroblast or dermal fibroblast. We harnessed lung fibroblast instead of dermal for wound healing because our previous work has shown that the decellularized ECM from lung fibroblast has a relatively higher level of ECM proteins and angiogenic cytokines than dermal fibroblast [26]. However, since angiogenic capability of the sFDM has not been examined, we conducted in vitro biological assay before the in vivo test.…”

Section: Discussionmentioning

confidence: 99%

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Nano-Sized Extracellular Matrix Particles Lead to Therapeutic Improvement for Cutaneous Wound and Hindlimb Ischemia

Kim

Savitri

et al. 2021

IJMS

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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.

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“…Several authors have proposed the use of ECM synthesized during in vitro culture of primary cells, known as cell-derived ECMs (CD-ECMs) (Ha et al, 2020;Savitri et al, 2020). Among the advantages of this approach are the maintenance of the ECM architecture and its availability depending on the desired cell-line products, as well as the reduction in immunogenic response and infectious disease transmission.…”

Section: Decellularized Extracellular Matrixmentioning

confidence: 99%

Decellularized Tissues for Wound Healing: Towards Closing the Gap Between Scaffold Design and Effective Extracellular Matrix Remodeling

David

Guiza-Arguello

Arango-Rodríguez

et al. 2022

Front. Bioeng. Biotechnol.

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The absence or damage of a tissue is the main cause of most acute or chronic diseases and are one of the appealing challenges that novel therapeutic alternatives have, in order to recover lost functions through tissue regeneration. Chronic cutaneous lesions are the most frequent cause of wounds, being a massive area of regenerative medicine and tissue engineering to have efforts to develop new bioactive medical products that not only allow an appropriate and rapid healing, but also avoid severe complications such as bacterial infections. In tissue repair and regeneration processes, there are several overlapping stages that involve the synergy of cells, the extracellular matrix (ECM) and biomolecules, which coordinate processes of ECM remodeling as well as cell proliferation and differentiation. Although these three components play a crucial role in the wound healing process, the ECM has the function of acting as a biological platform to permit the correct interaction between them. In particular, ECM is a mixture of crosslinked proteins that contain bioactive domains that cells recognize in order to promote migration, proliferation and differentiation. Currently, tissue engineering has employed several synthetic polymers to design bioactive scaffolds to mimic the native ECM, by combining biopolymers with growth factors including collagen and fibrinogen. Among these, decellularized tissues have been proposed as an alternative for reconstructing cutaneous lesions since they maintain the complex protein conformation, providing the required functional domains for cell differentiation. In this review, we present an in-depth discussion of different natural matrixes recently employed for designing novel therapeutic alternatives for treating cutaneous injuries, and overview some future perspectives in this area.

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Extracellular matrices derived from different cell sources and their effect on macrophage behavior and wound healing

Abstract: Decellularized extracellular matrix (dECM) is an excellent biomaterial in regenerative medicine, due to its biomimetic nature to target tissues and organs. In this study, we prepared cell-derived ECMs (CDM) derived...

Cited by 29 publications

References 44 publications

Decellularised Human Umbilical Artery as a Vascular Graft Elicits Minimal Pro-Inflammatory Host Response Ex Vivo and In Vivo

Decellularised Human Umbilical Artery as a Vascular Graft Elicits Minimal Pro-Inflammatory Host Response Ex Vivo and In Vivo

Nano-Sized Extracellular Matrix Particles Lead to Therapeutic Improvement for Cutaneous Wound and Hindlimb Ischemia

Decellularized Tissues for Wound Healing: Towards Closing the Gap Between Scaffold Design and Effective Extracellular Matrix Remodeling

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