Tofu-Based Hybrid Hydrogels with Antioxidant and Low Immunogenicity Activity for Enhanced Wound Healing

2019 ◽  
Vol 15 (7) ◽  
pp. 1371-1383 ◽  
Author(s):  
Jun Huang ◽  
Long Chen ◽  
Qijuan Yuan ◽  
Zhipeng Gu ◽  
Jun Wu

Free radicals and inflammation in the skin suffering from trauma cause oxidative damage and delayed healing, leading to adverse wound conditions. To adequately investigate the effects of free radicals and controlled immunogenicity for wound healing, we propose a tofu-based hybrid hydrogel with antioxidant and low immunogenicity properties that can be used for wound healing. Tofu, a food source material, was introduced for the first time into gelatin methacryloyl (GelMA) hydrogels by the photo-crosslinking method. The results demonstrated that the incorporation of tofu influenced the pores, swelling, water vapor transmission and compressive properties of hydrogels greatly. The antioxidant activities of hydrogels had been enhanced with increasing rations of tofu, and the fibroblast culture showed good proliferation on the hybrid hydrogels, as well as slight immunogenicity, thereby inducing the M2 differentiation of macrophages. Further, a full-thickness skin wound model was created to study the healing effect of hybrid hydrogels. In vivo results confirmed that the antioxidant activity and slight immunological stimulation properties of tofu hydrogels could accelerate the wound healing rate and improve the skin tissue regeneration effect. The present study validates that the tofu-based hybrid hydrogels have multiple bioactivities and could be potential antioxidant and immunoregulation hydrogels in wound healing applications.

Polymers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 3191
Author(s):  
Zari Pahlevanneshan ◽  
Mohammadreza Deypour ◽  
Amirhosein Kefayat ◽  
Mohammad Rafienia ◽  
Paweł Sajkiewicz ◽  
...  

This piece of research explores porous nanocomposite polyurethane (PU) foam synthesis, containing nanolignin (NL), coated with natural antimicrobial propolis for wound dressing. PU foam was synthesized using polyethylene glycol, glycerol, NL, and 1, 6-diisocyanato-hexane (NCO/OH ratio: 1.2) and water as blowing agent. The resultant foam was immersed in ethanolic extract of propolis (EEP). PU, NL-PU, and PU-NL/EEP foams were characterized from mechanical, morphological, and chemical perspectives. NL Incorporation into PU increased mechanical strength, while EEP coating showed lower strength than PU-NL/EEP. Morphological investigations confirmed an open-celled structure with a pore diameter of 150–200 μm, a density of nearly 0.2 g/cm3,, and porosity greater than 85%, which led to significantly high water absorption (267% for PU-NL/EEP). The hydrophilic nature of foams, measured by the contact angle, proved to be increased by NL addition and EEP coating. PU and PU-NL did not show important antibacterial features, while EEP coating resulted in a significant antibacterial efficiency. All foams revealed high biocompatibility toward L929 fibroblasts, with the highest cell viability and cell attachment for PU-NL/EEP. In vivo wound healing using Wistar rats’ full-thickness skin wound model confirmed that PU-NL/EEP exhibited an essentially higher wound healing efficacy compared with other foams. Hence, PU-NL/EEP foam could be a promising wound dressing candidate.


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.


Author(s):  
Fahim M. Mahmood ◽  
Hayder B. Sahib ◽  
Khalid W. Qassim

Wound healing is a complex physiological and dynamic process required the coordination of numerous cell types and biological processes to regenerate damaged tissue and initiate repair which is dependent on a number of inter-related factors. This study was aimed to demonstrate whether the ?2 receptor has role in wound healing and angiogenesis. A murine wild-type (in vivo), excisional skin wound model was done to demonstrate that activation of ?2AR delay wound repair, twenty-four male albino mice were used to investigate the effect of the drug on experimental wound healing grossly, histo-pathologically and immune-histochemically compared with vehicle-only controls. The results showed that the rate of wound healing was significantly slower in salbutamol group than in control group (P


2018 ◽  
Vol 49 (3) ◽  
pp. 1074-1089 ◽  
Author(s):  
Ying Zhao ◽  
Qiang Wang ◽  
Yuan Jin ◽  
Yadan Li ◽  
Changjun Nie ◽  
...  

Background/Aims: How to aid recovery from severe skin injuries, such as burns, chronic or radiation ulcers, and trauma, is a critical clinical problem. Current treatment methods remain limited, and the discovery of ideal wound-healing therapeutics has been a focus of research. Functional recombinant proteins such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have been developed for skin repair, however, some disadvantages in their use remain. This study reports the discovery of a novel small peptide targeting fibroblast growth factor receptor 2 IIIc (FGFR2IIIc) as a potential candidate for skin wound healing. Methods: A phage-displayed peptide library was used for biopanning FGFR2IIIc-targeting small peptides. The selected small peptides binding to FGFR2IIIc were qualitatively evaluated by an enzyme-linked immunosorbent assay. Their biological function was detected by a cell proliferation assay. Among them, an optimized small peptide named H1 was selected for further study. The affinity of the H1 peptide and FGFR2IIIc was determined by an isothermal titration calorimetry device. The ability of theH1 peptide to promote skin wound repair was investigated using an endothelial cell tube formation assay and wound healing scratch assay in vitro. Subsequently, the H1 peptide was assessed using a rat skin full-thickness wound model and chorioallantoic membrane (CAM) assays in vivo. To explore its molecular mechanisms, RNA-Seq, quantitative real-time PCR, and western blot assays were performed. Computer molecular simulations were also conducted to analyze the binding model. Results: We identified a novel FGFR2IIIc-targeting small peptide, called H1, with 7 amino acid residues using phage display. H1 had high binding affinity with FGFR2IIIc. The H1 peptide promoted the proliferation and motility of fibroblasts and vascular endothelial cells in vitro. In addition, the H1 peptide enhanced angiogenesis in the chick chorioallantoic membrane and accelerated wound healing in a rat full-thickness wound model in vivo. The H1 peptide activated both the PI3K-AKT and MAPK-ERK1/2 pathways and simultaneously increased the secretion of vascular endothelial growth factor. Computer analysis demonstrated that the model of H1 peptide binding to FGFR2IIIc was similar to that of FGF2 and FGFR2IIIc. Conclusion: The H1 peptide has a high affinity for FGFR2IIIc and shows potential as a wound healing agent. As a substitute for bFGF, it could be developed into a novel therapeutic candidate for skin wound repair in the future.


2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.


2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Jianhua Zhang ◽  
Junfei Hu ◽  
Baoshu Chen ◽  
Tianbao Zhao ◽  
Zhipeng Gu

Abstract Wound healing dressing is increasingly needed in clinical owing to the large quantity of skin damage annually. Excessive reactive oxygen species (ROS) produced through internal or external environmental influences can lead to lipid peroxidation, protein denaturation, and even DNA damage, and ultimately have harmful effects on cells. Aiming to sufficiently contact with the wound microenvironment and scavenge ROS, superabsorbent poly (acrylic acid) and antioxidant poly (ester amide) (PAA/PEA) hybrid hydrogel has been developed to enhance wound healing. The physical and chemical properties of hybrid hydrogels were studied by Fourier-transform infrared (FTIR) absorption spectrum, compression, swelling, degradation, etc. Besides, the antioxidant properties of hybrid hydrogels can be investigated through the free radical scavenging experiment, and corresponding antioxidant indicators have been tested at the cellular level. Hybrid hydrogel scaffolds supported the proliferation of human umbilical vein endothelial cells and fibroblasts, as well as accelerated angiogenesis and skin regeneration in wounds. The healing properties of wounds in vivo were further assessed on mouse skin wounds. Results showed that PAA/PEA hybrid hydrogel scaffolds significantly accelerated the wound healing process through enhancing granulation formation and re-epithelialization. In summary, these superabsorbent and antioxidative hybrid hydrogels could be served as an excellent wound dressing for full-thickness wound healing.


2013 ◽  
Vol 135 (10) ◽  
Author(s):  
Clare Y. L. Chao ◽  
Gabriel Y. F. Ng ◽  
Kwok-Kuen Cheung ◽  
Yong-Ping Zheng ◽  
Li-Ke Wang ◽  
...  

An evaluation of wound mechanics is crucial in reflecting the wound healing status. The present study examined the biomechanical properties of healing rat skin wounds in vivo and ex vivo. Thirty male Sprague-Dawley rats, each with a 6 mm full-thickness circular punch biopsied wound at both posterior hind limbs were used. The mechanical stiffness at both the central and margins of the wound was measured repeatedly in five rats over the same wound sites to monitor the longitudinal changes over time of before wounding, and on days 0, 3, 7, 10, 14, and 21 after wounding in vivo by using an optical coherence tomography-based air-jet indentation system. Five rats were euthanized at each time point, and the biomechanical properties of the wound tissues were assessed ex vivo using a tensiometer. At the central wound bed region, the stiffness measured by the air-jet system increased significantly from day 0 (17.2%), peaked at day 7 (208.3%), and then decreased progressively until day 21 (40.2%) as compared with baseline prewounding status. The biomechanical parameters of the skin wound samples measured by the tensiometer showed a marked reduction upon wounding, then increased with time (all p < 0.05). On day 21, the ultimate tensile strength of the skin wound tissue approached 50% of the normal skin; while the stiffness of tissue recovered at a faster rate, reaching 97% of its prewounded state. Our results suggested that it took less time for healing wound tissues to recover their stiffness than their maximal strength in rat skin. The stiffness of wound tissues measured by air-jet could be an indicator for monitoring wound healing and contraction.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kareem Abdelsaid ◽  
Sudhahar Varadarajan ◽  
Archita Das ◽  
Yutao Liu ◽  
Xuexiu Fang ◽  
...  

Background: Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) have detrimental effects. Exercise not only improves endothelial dysfunction and angiogenesis in T2DM but also induces secretion of exosomes into circulation. Extracellular superoxide dismutase (ecSOD) is a major secretory Cu containing antioxidant enzyme that catalyzes dismutation of O 2 •- to H 2 O 2 and its full activity requires Cu transporter ATP7A. We reported that ecSOD-derived H 2 O 2 in endothelial cells (ECs) enhances angiogenesis while impaired ATP7A-ecSOD axis in diabetes induces endothelial dysfunction. Here we examined whether exercise-derived exosomes (Exe-Exo) may have pro-angiogenic effects via regulating ATP7A-ecSOD axis in T2DM. Results: Two weeks of voluntary wheel exercise of control C57Bl6 mice increased plasma exosome levels (6.2-fold) characterized by Nanosight, TEM and exosome markers (CD63, CD81, Tsg101). Treatment of HUVECs with equal number of exosomes revealed that angiogenic responses such as EC migration (1.8-fold) and tube formation (1.7-fold) were significantly enhanced by Exe-Exo compared to sedentary-derived exosomes (Sed-Exo). This was associated with increased ATP7A (2.9-fold) and ecSOD (1.4-fold) expression in Exe-Exo. Sed-Exo from high fat-induced T2DM mice significantly decreased EC migration (40%) and tube formation (10%) as well as ATP7A expression (28%) compared to Sed-Exo from control mice, which were restored by T2DM Exe-Exo, but not by T2DM/ecSOD KO Exe-Exo. Furthermore, exosomes overexpressing ecSOD (ecSOD-Exo) which mimic exercise increased angiogenesis and H2O2 levels in ECs, which were inhibited by overexpression of catalase. In vivo, skin wound healing model showed that direct application of T2DM Sed-Exo delayed while T2DM Exe-Exo enhanced wound healing of control mice. Furthermore, defective wound healing in T2DM mice or ecSOD KO mice were rescued by ecSOD-Exo application. Conclusion: Exercise training improves pro-angiogenic function of circulating exosomes in T2DM via increasing ATP7A-ecSOD axis, which may provide an effective therapy for promoting angiogenesis and wound repair in metabolic and cardiovascular diseases.


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