scholarly journals Prevention of excessive scar formation using nanofibrous meshes made of biodegradable elastomer poly(3-hydroxybutyrate-co-3-hydroxyvalerate)

2020 ◽  
Vol 11 ◽  
pp. 204173142094933 ◽  
Author(s):  
Hye Sung Kim ◽  
Junyu Chen ◽  
Lin-Ping Wu ◽  
Jihua Wu ◽  
Hua Xiang ◽  
...  

To reduce excessive scarring in wound healing, electrospun nanofibrous meshes, composed of haloarchaea-produced biodegradable elastomer poly(3-hydroxybutyrate- co-3-hydroxyvalerate) (PHBV), are fabricated for use as a wound dressing. Three PHBV polymers with different 3HV content are used to prepare either solution-cast films or electrospun nanofibrous meshes. As 3HV content increases, the crystallinity decreases and the scaffolds become more elastic. The nanofibrous meshes exhibit greater elasticity and elongation at break than films. When used to culture human dermal fibroblasts in vitro, PHBV meshes give better cell attachment and proliferation, less differentiation to myofibroblasts, and less substrate contraction. In a full-thickness mouse wound model, treatment with films or meshes enables regeneration of pale thin tissues without scabs, dehydration, or tubercular scar formation. The epidermis of wounds treated with meshes develop small invaginations in the dermis within 2 weeks, indicating hair follicle and sweat gland regeneration. Consistent with the in vitro results, meshes reduce myofibroblast differentiation in vivo through downregulation of α-SMA and TGF-β1, and upregulation of TGF-β3. The regenerated wounds treated with meshes are softer and more elastic than those treated with films. These results demonstrate that electrospun nanofibrous PHBV meshes mitigate excessive scar formation by regulating myofibroblast formation, showing their promise for use as wound dressings.

2021 ◽  
Author(s):  
Shune Xiao ◽  
Chunfang Xiao ◽  
Yong Miao ◽  
Jin Wang ◽  
Ruosi Chen ◽  
...  

Abstract Background: Diabetic wounds threaten the health and quality of life of patients and their treatment remains challenging. ADSC-derived exosomes have shown encouraging results in enhancing diabetic wound healing. However, the common method of exosome administration is subcutaneous injection at several sites around the wound, causing further damage and preventing direct contact between the exosomes and the injury site. Methods: A diabetic mouse skin wound model was established. ADSC-derived exosomes (ADSC-Exos) were isolated and in vitro application of exosomes was evaluated using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblasts (HDFs). After preparation and characterization of a scaffold of human acellular amniotic membrane (hAAM) loaded with ADSC-Exos in vitro , they were transplanted into wounds in vivo and wound healing phenomena were observed by histological and immunohistochemical analyses to identify the wound healing mechanism of the exosome-hAAM composites. Results: The hAAM scaffold dressing was very suitable for the delivery of exosomes. ADSC-Exos enhanced the proliferation and migration of HDFs and promoted proliferation and tube formation of HUVECs in vitro . In vivo results from a diabetic skin wound model showed that the hAAM-Exos dressing accelerated wound healing by regulating inflammation, stimulating vascularization and promoting the production of extracellular matrix. Conclusion: Exosome-incorporated hAAM scaffolds showed great potential in promoting diabetic skin wound healing, while also providing strong evidence for the future clinical applications of ADSC-derived exosomes.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shune Xiao ◽  
Chunfang Xiao ◽  
Yong Miao ◽  
Jin Wang ◽  
Ruosi Chen ◽  
...  

Abstract Background Diabetic wounds threaten the health and quality of life of patients and their treatment remains challenging. ADSC-derived exosomes have shown encouraging results in enhancing diabetic wound healing. However, how to use exosomes in wound treatment effectively is a problem that needs to be addressed at present. Methods A diabetic mouse skin wound model was established. ADSC-derived exosomes (ADSC-Exos) were isolated, and in vitro application of exosomes was evaluated using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblasts (HDFs). After preparation and characterization of a scaffold of human acellular amniotic membrane (hAAM) loaded with ADSC-Exos in vitro, they were transplanted into wounds in vivo and wound healing phenomena were observed by histological and immunohistochemical analyses to identify the wound healing mechanism of the exosome-hAAM composites. Results The hAAM scaffold dressing was very suitable for the delivery of exosomes. ADSC-Exos enhanced the proliferation and migration of HDFs and promoted proliferation and tube formation of HUVECs in vitro. In vivo results from a diabetic skin wound model showed that the hAAM-Exos dressing accelerated wound healing by regulating inflammation, stimulating vascularization, and promoting the production of extracellular matrix. Conclusion Exosome-incorporated hAAM scaffolds showed great potential in promoting diabetic skin wound healing, while also providing strong evidence for the future clinical applications of ADSC-derived exosomes.


2021 ◽  
Vol 30 (9) ◽  
pp. 729-736
Author(s):  
Vera Grotheer ◽  
Joachim Windolf ◽  
Christoph V Suschek

Hard-to-heal wounds represent an increasing health and economic burden on society. At present, therapy options for hard-to-heal wounds are often unsatisfactory, and the development of more effective wound treatments is urgently needed. We have shown that orthosilicic acid-releasing silica fibre fleece (SIFIB), via its pronounced anti-inflammatory properties, exhibited a significantly enhanced effect on wound closure kinetics in a porcine wound model in vivo. In this present study, we have examined in vitro the impact of the pro-angiogenic potential of SIFIB. Using an in vitro angiogenesis assay we describe for the first time how an inorganic biodegradable silica-based material significantly improved endothelial microvessel-like structure formation. We further demonstrate that the molecular mechanism of this pro-angiogenic activity of SIFIB is based on a significantly increased and tumour necrosis factor (TNF)α-dependent VEGF protein expression. In conclusion, due to its positive effects on angiogenesis, our results further indicate that decomposition products of silica-based biodegradable inorganic materials might represent very relevant therapeutic components of modern wound dressings for the treatment of hard-to-heal wounds.


2019 ◽  
Vol 33 (9) ◽  
pp. 1285-1297 ◽  
Author(s):  
Cornelia Wiegand ◽  
Martin Abel ◽  
Uta-Christina Hipler ◽  
Peter Elsner ◽  
Michael Zieger ◽  
...  

Background Application of controlled in vitro techniques can be used as a screening tool for the development of new hemostatic agents allowing quantitative assessment of overall hemostatic potential. Materials and methods Several tests were selected to evaluate the efficacy of cotton gauze, collagen, and oxidized regenerated cellulose for enhancing blood clotting, coagulation, and platelet activation. Results Visual inspection of dressings after blood contact proved the formation of blood clots. Scanning electron microscopy demonstrated the adsorption of blood cells and plasma proteins. Significantly enhanced blood clot formation was observed for collagen together with β-thromboglobulin increase and platelet count reduction. Oxidized regenerated cellulose demonstrated slower clotting rates not yielding any thrombin generation; yet, led to significantly increased thrombin-anti-thrombin-III complex levels compared to the other dressings. As hemostyptica ought to function without triggering any adverse events, induction of hemolysis, instigation of inflammatory reactions, and initiation of the innate complement system were also tested. Here, cotton gauze provoked high PMN elastase and elevated SC5b-9 concentrations. Conclusions A range of tests for desired and undesired effects of materials need to be combined to gain some degree of predictability of the in vivo situation. Collagen-based dressings demonstrated the highest hemostyptic properties with lowest adverse reactions whereas gauze did not induce high coagulation activation but rather activated leukocytes and complement.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Cynthia St. Hilaire ◽  
Hui Jin ◽  
Yuting Huang ◽  
Dan Yang ◽  
Alejandra Negro ◽  
...  

Objective: The objective of this study was to develop a patient-specific induced pluripotent stem cell (iPSC)-based disease model to understand the process by which CD73-deficiency leads to vascular calcification in the disease, Arterial Calcification due to Deficiency of CD73 (ACDC). Approach & Results: ACDC is an autosomal recessive disease resulting from mutations in the gene encoding for CD73, which converts extracellular AMP to adenosine. CD73-deficiency manifests with tortuosity and vascular calcification of the medial layer of lower-extremity arteries, a pathology associated with diabetes and chronic kidney disease. We previously identified that dermal fibroblasts isolated from ACDC patients calcify in vitro, however in vivo studies of the vasculature are limited, as murine models of CD73 deficiency do not recapitulate the human disease phenotype. Thus, we created iPSCs from ACDC patients and control fibroblasts. ACDC and Control iPSCs form teratomas when injected in immune-compromised mice, however ACDC iPSC teratomas exhibit extensive calcifications. Control and ACDC iPSCs were differentiated down the mesenchymal lineage (MSC) and while there was no difference in chondrogenesis and adipogenesis, ACDC iMSCs underwent osteogenesis sooner than control iPSC, have higher activity of tissue-nonspecific alkaline phosphatase (TNAP), and lower levels of extracellular adenosine. During osteogenic simulation, TNAP activity in ACDC cells significantly increased adenosine levels, however, not to levels needed for functional compensatory stimulation of the adenosine receptors. Inhibition of TNAP with levimisole ablates this increase in adenosine. Treatment with an A2b adenosine receptor (AR) agonist drastically reduced TNAP activity in vitro, and calcification in ACDC teratomas, as did treatment with etidronate, which is currently being tested in a clinical trial on ACDC patients. Conclusions: These results illustrate a pro-osteogenic phenotype in CD73-deficient cells whereby TNAP activity attempts to compensate for CD73 deficiency, but subsequently induces calcification that can be reversed by activation of the A2bAR. The iPSC teratoma model may be used to screen other potential therapeutics for calcification disorders.


1991 ◽  
pp. 131-135 ◽  
Author(s):  
C. Mahaza ◽  
R. Robert ◽  
M. Miègeville ◽  
G. Tronchin ◽  
J. M. Senet

Author(s):  
Gil Topman ◽  
Orna Sharabani-Yosef ◽  
Amit Gefen

A wound healing assay is simple but effective method to study cell migration in vitro. Cell migration in vitro was found to mimic migration in vivo to some extent [1,2]. In wound healing assays, a “wound” is created by either scraping or mechanically crushing cells in a monolayer, thereby forming a denuded area. Cells migrate into the denuded area to complete coverage, and thereby “heal” the wound. Micrographs at regular time intervals are captured during such experiments for analysis of the process of migration.


2020 ◽  
Author(s):  
Afshin Fathi ◽  
Mehdi Khanmohammadi ◽  
Arash Goodarzi ◽  
Lale Foroutani ◽  
Zahra Taherian Mobarakeh ◽  
...  

Abstract Hybrid fibrous mat containing cell interactive molecules offers the ability to deliver the cells and drugs in wound bed, which will help to achieve a high therapeutic treatment. In this study, a co-electrospun hybrid of polyvinyl alcohol (PVA), chitosan (Ch) and silk fibrous mat was developed and their wound healing potential by localizing bone marrow mesenchymal stem cells (MSCs)-derived keratinocytes on it was evaluated in vitro and in vivo. It was expected that fabricated hybrid construct could promote wound healing due to its structure, physical, biological specifications. The fabricated fibrous mats were characterized for their structural, mechanical and biochemical properties. The shape uniformity and pore size of fibers showed smooth and homogenous structures of them. Fourier transform infrared spectroscopy (FTIR) verified all typical absorption characteristics of Ch-PVA + Silk polymers as well as Ch-PVA or pure PVA substrates. The contact angle and wettability measurement of fibers showed that mats found moderate hydrophilicity by addition of Ch and silk substrates compared with PVA alone. The mechanical features of Ch-PVA + Silk fibrous mat increase significantly through co-electrospun process as well as hybridization of these synthetic and natural polymers. Higher degrees of cellular attachment and proliferation obtained on Ch-PVA + Silk fibers compared with PVA and Ch-PVA fibers. In terms of the capability of Ch-PVA + Silk fibers and MSC-derived keratinocytes, histological analysis and skin regeneration results showed this novel fibrous construct could be suggested as a skin substitute in the repair of injured skin and regenerative medicine applications.


2020 ◽  
Author(s):  
Samuel Schmidt ◽  
Bettina Weigelin ◽  
Joost te Riet ◽  
Veronika te Boekhorst ◽  
Mariska te Lindert ◽  
...  

SummaryCell migration is a force-dependent adaptive process mediated by integrin-dependent adhesion as well as other yet poorly defined interactions to the extracellular matrix. Using enzymatic multi-targeted digestion of sugar moieties on the surface of mesenchymal cells and leukocytes after interference with integrin function, we demonstrate that the surface glycocalyx represents an independent adhesion system. The glycocalyx mediates cell attachment to ECM ligand in the 100-500 pN force range and amoeboid migration in 3D environments in vitro and in vivo. Glycan-based adhesions consist of actin-rich membrane deformations and appositions associated with bleb-like and other protrusions forming complex-shaped sub-micron contact sites to ECM fibrils. These data implicate the glycocalyx in mediating generic stickiness to support nanoscale interactions (nanogrips) between the cell surface and ECM, mechano-coupling, and migration.


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