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Review
. 2022 Jul 28:13:20417314221114273.
doi: 10.1177/20417314221114273. eCollection 2022 Jan-Dec.

Cell secretomes for wound healing and tissue regeneration: Next generation acellular based tissue engineered products

Nur Izzah Md Fadilah  1 , Muhammad Syahiran Mohd Abdul Kader Jailani  1 , Muhd Aliff Iqmal Badrul Hisham  1 , Nithiaraj Sunthar Raj  1 , Sharen Aini Shamsuddin  1 , Min Hwei Ng  1 , Mh Busra Fauzi  1 , Manira Maarof  1
Affiliations
Review

Cell secretomes for wound healing and tissue regeneration: Next generation acellular based tissue engineered products

Nur Izzah Md Fadilah et al. J Tissue Eng. .

Abstract

Wound represents a significant socioeconomic burden for both affected individuals and as a whole healthcare system. Accordingly, stem cells have garnered attention due to their differentiation capacity and ability to aid tissue regeneration by releasing biologically active molecules, found in the cells' cultivated medium which known as conditioned medium (CM) or secretomes. This acellular approach provides a huge advantage over conventional treatment options, which are mainly used cellular treatment at wound closure. Interestingly, the secretomes contained the cell-secreted proteins such as growth factors, cytokines, chemokines, extracellular matrix (ECM), and small molecules including metabolites, microvesicles, and exosomes. This review aims to provide a general view on secretomes and how it is proven to have great potential in accelerating wound healing. Utilizing the use of secretomes with its secreted proteins and suitable biomaterials for fabrications of acellular skin substitutes can be promising in treating skin loss and accelerate the healing process.

Keywords: Secretomes; conditioned medium; secreted protein; tissue regeneration; wound healing.

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Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Schematic image of the human skin barrier function and protection with wound-based dressing material against wound infection bacteria. An ideal dressing should be biocompatible and biodegradable, maintain the moisture, be permeable to oxygen, enable the exudate removal, prevent the wound from pathogens and mechanical irritation, improve cell behaviors, and promote wound healing. Image created with Biorender.com.
Figure 2.
Figure 2.
Exosomes and important cells involved in diabetic wound healing. Exosomes can promote endothelial cell function recovery and angiogenesis through activating the Erk1/2signaling pathway or activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1β, and increasing the secretion of VEGF, IGF-1, and FGF. Exosomes inhibit inflammation by promoting phenotypic changes of macrophages by activating the PTEN/Akt signaling pathway. Exosomes promote proliferation and migration of fibroblasts by activation of PI3K/Akt pathways or activating the Rho-YAP signaling pathway exosomes promote the proliferation and migration of keratinocytes. The figure is reprinted (adapted) with permission from reference under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Figure 3.
Figure 3.
Secretomes promoted wound healing and inhibits scar formation in vivo. (a) Compared with the control and MPF, MPF@CM promotes skin regeneration in vivo. Statistical analysis of the healing of (b) skin defect and (c) scar area (Average ± SD, n = 3 for each group, *denotes p < 0.05, **denotes p < 0.01, and ***denotes p < 0.0001 by One-way ANOVA followed by Tukey’s multiple comparison test). Figure (a–c) reprinted (adapted) with permission from reference under the terms of the CC-BY-NC-ND license (http>//creativecommons.org/license/BY-NC-ND/4.0/).
Figure 4.
Figure 4.
A staged schematic of (a) a traditional engineered skin graft implanted onto the injured skin formation and (b) fabrication of secretomes with biomaterials for of 3D acellular skin substitute.
Figure 5.
Figure 5.
Mechanism of wound healing using secretomes. The stem cell secretomes may promote wound healing by stimulating the proliferative and migratory abilities of skin cells.
See this image and copyright information in PMC

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