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Article ; Online: Extracellular vesicle biopotentiated hydrogels for diabetic wound healing

Zhenzhen Yan / Tinglin Zhang / Yuxiang Wang / Shichu Xiao / Jie Gao

Materials Today Bio, Vol 23, Iss , Pp 100810- (2023)

The art of living nanomaterials combined with soft scaffolds

2023

Abstract: Diabetic wounds (DWs) pose a major challenge for the public health system owing to their high incidence, complex pathogenesis, and long recovery time; thus, there is an urgent need to develop innovative therapies to accelerate the healing process of ... ...

Abstract	Diabetic wounds (DWs) pose a major challenge for the public health system owing to their high incidence, complex pathogenesis, and long recovery time; thus, there is an urgent need to develop innovative therapies to accelerate the healing process of diabetic wounds. As natural nanovesicles, extracellular vesicles (EVs) are rich in sources with low immunogenicity and abundant nutritive molecules and exert potent therapeutic effects on diabetic wound healing. To avoid the rapid removal of EVs, a suitable delivery system is required for their controlled release. Owing to the advantages of high porosity, good biocompatibility, and adjustable physical and chemical properties of hydrogels, EV biopotentiated hydrogels can aid in achieving precise and favorable therapy against diabetic wounds. This review highlights the different design strategies, therapeutic effects, and mechanisms of EV biopotentiated hydrogels. We also discussed the future challenges and opportunities of using EV biopotentiated hydrogels for diabetic wound healing.
Keywords	Diabetic wounds ; Extracellular vesicle ; Hydrogel ; Design strategy ; Mechanism ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Severe skin and soft tissue infection in the left upper limb caused by Aeromonas veronii

Linhui Li / Jie Huang / Long Xu / Guangyi Wang / Shichu Xiao / Zhaofan Xia / Qin Qin / Yazhou Li / Shizhao Ji

Journal of Medical Case Reports, Vol 17, Iss 1, Pp 1-

a case report

2023 Volume 5

Abstract: Abstract Introduction Skin and soft tissue infections are common because of exposure to aquatic environment, while severe infections caused by Aeromonas veronii are rare. Case presentation We report a case of severe skin and soft tissue infection of the ... ...

Abstract	Abstract Introduction Skin and soft tissue infections are common because of exposure to aquatic environment, while severe infections caused by Aeromonas veronii are rare. Case presentation We report a case of severe skin and soft tissue infection of the left upper limb caused by Aeromonas veronii. A 50-year-old Chinese woman, who had a history of cardiac disease and type 2 diabetes mellitus, accidentally injured her left thumb while cutting a fish. Early antibiotic therapy and surgical debridement was performed before the result of bacterial culture came back. Whole-genome sequencing was further performed to confirm the pathogen and reveal the drug resistance and virulence genes. The wound was gradually repaired after 1 month of treatment, and the left hand recovered well in appearance and function after 3 months of rehabilitation. Conclusion Early diagnosis, surgical intervention, and administration of appropriate antibiotics are crucial for patients who are suspected of having skin and soft tissue infection, or septicemia caused by Aeromonas veronii.
Keywords	Aeromonas veronii ; Wound infection ; Antibiotic therapy ; Whole-genome sequencing ; Case report ; Medicine ; R
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Acceleration of burn wound healing by micronized amniotic membrane seeded with umbilical cord-derived mesenchymal stem cells

Zixuan Zhou / Jingnan Xun / Chenghao Wu / Chao Ji / Shizhao Ji / Futing Shu / Yuxiang Wang / Hao Chen / Yongjun Zheng / Shichu Xiao

Materials Today Bio, Vol 20, Iss , Pp 100686- (2023)

2023

Abstract: Umbilical cord-derived mesenchymal stem cells (UC-MSC) are promising candidates for wound healing. However, the low amplification efficiency of MSC in vitro and their low survival rates after transplantation have limited their medical application. In ... ...

Abstract	Umbilical cord-derived mesenchymal stem cells (UC-MSC) are promising candidates for wound healing. However, the low amplification efficiency of MSC in vitro and their low survival rates after transplantation have limited their medical application. In this study, we fabricated a micronized amniotic membrane (mAM) as a microcarrier to amplify MSC in vitro and used mAM and MSC (mAM-MSC) complexes to repair burn wounds. Results showed that MSC could live and proliferate on mAM in a 3D culture system, exhibiting higher cell activity than in 2D culture. Transcriptome sequencing of MSC showed that the expression of growth factor-related, angiogenesis-related, and wound healing-related genes was significantly upregulated in mAM-MSC compared to traditional 2D-cultured MSC, which was verified via RT-qPCR. Gene ontology (GO) analysis of differentially expressed genes (DEGs) showed significant enrichment of terms related to cell proliferation, angiogenesis, cytokine activity, and wound healing in mAM-MSC. In a burn wound model of C57BL/6J mice, topical application of mAM-MSC significantly accelerated wound healing compared to MSC injection alone and was accompanied by longer survival of MSC and greater neovascularization in the wound.
Keywords	Burn wound healing ; Microcarrier ; Amniotic membrane ; Umbilical cord-derived mesenchymal stem cells ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Biomimetic Alginate/Gelatin Cross-Linked Hydrogels Supplemented with Polyphosphate for Wound Healing Applications

Shunfeng Wang / Xiaohong Wang / Meik Neufurth / Emad Tolba / Hadrian Schepler / Shichu Xiao / Heinz C. Schröder / Werner E. G. Müller

Molecules, Vol 25, Iss 5210, p

2020 Volume 5210

Abstract: In the present study, the fabrication of a biomimetic wound dressing that mimics the extracellular matrix, consisting of a hydrogel matrix composed of non-oxidized and periodate-oxidized marine alginate, was prepared to which gelatin was bound via Schiff ...

Abstract	In the present study, the fabrication of a biomimetic wound dressing that mimics the extracellular matrix, consisting of a hydrogel matrix composed of non-oxidized and periodate-oxidized marine alginate, was prepared to which gelatin was bound via Schiff base formation. Into this alginate/oxidized-alginate-gelatin hydrogel, polyP was stably but reversibly integrated by ionic cross-linking with Zn 2+ ions. Thereby, a soft hybrid material is obtained, consisting of a more rigid alginate scaffold and porous structures formed by the oxidized-alginate-gelatin hydrogel with ionically cross-linked polyP. Two forms of the Zn-polyP-containing matrices were obtained based on the property of polyP to form, at neutral pH, a coacervate—the physiologically active form of the polymer. At alkaline conditions (pH 10), it will form nanoparticles, acting as a depot that is converted at pH 7 into the coacervate phase. Both polyP-containing hydrogels were biologically active and significantly enhanced cell growth/viability and attachment/spreading of human epidermal keratinocytes compared to control hydrogels without any adverse effect on reconstructed human epidermis samples in an in vitro skin irritation test system. From these data, we conclude that polyP-containing alginate/oxidized-alginate-gelatin hydrogels may provide a suitable regeneratively active matrix for wound healing for potential in vivo applications.
Keywords	inorganic polyphosphate ; coacervate ; nanoparticles ; alginate ; periodate oxidation ; gelatin ; Organic chemistry ; QD241-441
Subject code	540
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Human amnion-derived mesenchymal stem cells alleviate lung injury induced by white smoke inhalation in rats

Pei Cui / Haiming Xin / Yongming Yao / Shichu Xiao / Feng Zhu / Zhenyu Gong / Zhiping Tang / Qiu Zhan / Wei Qin / Yanhua Lai / Xiaohui Li / Yalin Tong / Zhaofan Xia

Stem Cell Research & Therapy, Vol 9, Iss 1, Pp 1-

2018 Volume 11

Abstract: Abstract Background White smoke inhalation (WSI) is an uncommon but potentially deadly cause of acute lung injury and acute respiratory distress syndrome for which no effective pharmaceutical treatment has been developed. This study aimed to determine ... ...

Abstract	Abstract Background White smoke inhalation (WSI) is an uncommon but potentially deadly cause of acute lung injury and acute respiratory distress syndrome for which no effective pharmaceutical treatment has been developed. This study aimed to determine the protective effects of human amnion-derived mesenchymal stem cells (hAMSCs) against WSI-induced lung injury in rats. Methods hAMSCs were injected into rats via the tail vein 4 h after WSI. At 1, 3, 7, 14, and 28 days after cell injection, hAMSCs labeled with PKH26 in lung, heart, liver, and kidney tissues were observed by fluorescence microscopy. The lung injury score was determined by hematoxylin and eosin staining. Lung fibrosis was assessed by Masson’s trichrome staining. The computed tomography (CT) score was assessed by CT scanning. The wet/dry weight ratio was calculated. The levels of interleukin (IL)-1β, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assays. The expression of surfactant protein (SP)-A, SP-C, and SP-D was measured by Western blotting. Results The injected hAMSCs were primarily distributed in the lung tissues in WSI-induced rats. Compared with the model and phosphate-buffered saline (PBS) group, hAMSC treatment led to reduced lung injury, lung fibrosis, CT score, and inflammation levels in WSI-induced mice. hAMSC treatment also resulted in increased cell retention in the lung, partial pressure of oxygen (PaO2), and PaO2/fraction of inspired oxygen (FiO2) levels, and pulmonary SP-A, SP-C, and SP-D expression compared with that in the model and PBS group. Conclusions hAMSCs are a potential cell-based therapy for WSI-induced lung injury.
Keywords	White smoke inhalation ; Human amnion-derived mesenchymal stem cells ; Lung injury ; Cell-based therapy ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	610
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: Amniotic Epithelial Cells Accelerate Diabetic Wound Healing by Modulating Inflammation and Promoting Neovascularization

Yongjun Zheng / Shiqing Zheng / Xiaoming Fan / Li Li / Yongqiang Xiao / Pengfei Luo / Yingying Liu / Li Wang / Zhenci Cui / Fei He / Yuhuan Liu / Shichu Xiao / Zhaofan Xia

Stem Cells International, Vol

2018 Volume 2018

Abstract: Human amniotic epithelial cells (hAECs) are nontumorigenic, highly abundant, and low immunogenic and possess multipotent differentiation ability, which make them become ideal alternative stem cell source for regenerative medicine. Previous studies have ... ...

Abstract	Human amniotic epithelial cells (hAECs) are nontumorigenic, highly abundant, and low immunogenic and possess multipotent differentiation ability, which make them become ideal alternative stem cell source for regenerative medicine. Previous studies have demonstrated the therapeutic potential of hAECs in many tissue repairs. However, the therapeutic effect of hAECs on diabetic wound healing is still unknown. In this study, we injected hAECs intradermally around the full-thickness excisional skin wounds of db/db mice and found that hAECs significantly accelerated diabetic wound healing and granulation tissue formation. To explore the underlying mechanisms, we measured inflammation and neovascularization in diabetic wounds. hAECs could modulate macrophage phenotype toward M2 macrophage, promote switch from proinflammatory status to prohealing status of wounds, and increase capillary density in diabetic wounds. Furthermore, we found that the hAEC-conditioned medium promoted macrophage polarization toward M2 phenotype and facilitated migration, proliferation, and tube formation of endothelial cells through in vitro experiments. Taken together, we first reported that hAECs could promote diabetic wound healing, at least partially, through paracrine effects to regulate inflammation and promote neovascularization.
Keywords	Internal medicine ; RC31-1245
Subject code	571
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Short- and long-term outcomes of small auto- and cryopreserved allograft skin grafting in those with >60%TBSA deep burn wounds.

Shizhao, Ji / Yongjun, Zheng / Lisen, Zhang / Pengfei, Luo / Xiaopeng, Zheng / Guangyi, Wang / Shihui, Zhu / Xiaoyan, Hu / Shichu, Xiao / Zhaofan, Xia

Burns : journal of the International Society for Burn Injuries

2017 Volume 43, Issue 1, Page(s) 206–214

Abstract: Background: The shortage of autologous skin sources not only adds difficulty to the repair of extremely large-area deep burn wounds but affects the healing quality. The aim of the present study is to explore an ideal method for repairing large-areas ... ...

Abstract	Background: The shortage of autologous skin sources not only adds difficulty to the repair of extremely large-area deep burn wounds but affects the healing quality. The aim of the present study is to explore an ideal method for repairing large-areas burn wounds with low scar formation. Methods: Between 2002 and 2014, we used grafting of small auto- and cryopreserved allo-skin to repair large-area residual burn wounds in wounds after 21 days 21 patients, and after early excision in 17 patients. The wound healing rate and quality were observed. Results: The skin expansion rate was 1:9-1:16, and the mean area of wounds repaired after three weeks was 64.8±7.3%TBSA, the wound healing rate was 91.8±3.7%. The mean area of the early excision group was 65.9±9.8 TBSA, where the healing rate was 94.5±5.6%. After small auto- and cryopreserved allograft skin grafting, the epidermis of the auto-skin gradually replaced the allo-epidermis, and the allo-dermis persisted for a prolonged period. The dermal collagen fibers at the allo-skin grafting sites were well arranged. At 1-2-year follow-up, observation showed that the Vancouver Scar Scale total score was 4·304±2·363, and we did not discern significant contracture and dysfunction in the large joints of the four extremities. Conclusions: Small auto- and cryopreserved allograft skin grafting of small auto- and allo-skin not only raised the graft expansion rate but offers a stable wound healing rate. This new technique may provide an option for repair of large-area deep burn wounds.
MeSH term(s)	Adult ; Body Surface Area ; Burns/complications ; Burns/surgery ; Cicatrix/etiology ; Contracture/etiology ; Cryopreservation ; Dermis/transplantation ; Epidermis/transplantation ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Skin Transplantation/methods ; Transplant Donor Site ; Transplantation, Autologous/methods ; Transplantation, Homologous/methods ; Trauma Severity Indices ; Treatment Outcome ; Wound Healing
Language	English
Publishing date	2017-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	197308-3
ISSN	1879-1409 ; 0305-4179
ISSN (online)	1879-1409
ISSN	0305-4179
DOI	10.1016/j.burns.2016.07.017
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Article: Topical administration of cryopreserved living micronized amnion accelerates wound healing in diabetic mice by modulating local microenvironment

Zheng, Yongjun / Shizhao Ji / Haibin Wu / Song Tian / Yunqing Zhang / Li Wang / He Fang / Pengfei Luo / Xingtong Wang / Xiaoyan Hu / Shichu Xiao / Zhaofan Xia

Biomaterials. 2017 Jan., v. 113

2017

Abstract: Approximately 25% of diabetic patients suffer from diabetic lower-extremity ulcer throughout their lives and 7%â20% of patients will eventually need an amputation despite standard care treatment. The development of new therapies to treat diabetic ... ...

Abstract	Approximately 25% of diabetic patients suffer from diabetic lower-extremity ulcer throughout their lives and 7%â20% of patients will eventually need an amputation despite standard care treatment. The development of new therapies to treat diabetic wounds is urgent. In this study, we used cryopreserved living micronized amnion (300â600Â Î¼m) to treat wounds in diabetic mice. Post-thaw micronized amnion retained high cell viability, as well as intact cell morphology and membrane structure. When transplanted onto the wounds of db/db mice, the cryopreserved living micronized amnion greatly promoted wound healing in diabetic mice mainly by secreting growth, inflammation, and chemotaxis-related factors that regulated macrophage migration and phenotype switch, recruited CD34+ progenitor cells, and increased neovascularization. In addition, the micronized amnion matrix can exist in the dermis and serve as a long-term dermal scaffold. These results demonstrated the potential of the cryopreserved living micronized amnion as a ready-to-use living dermal substitute that addresses multiple defective physiological processes of impaired wounds to treat diabetic ulcers and other chronic wounds in clinics.
Keywords	amnion ; amputation ; angiogenesis ; animal disease models ; cell viability ; cryopreservation ; dermis ; diabetes ; inflammation ; macrophages ; mice ; patients ; phenotype ; stem cells ; tissue repair
Language	English
Dates of publication	2017-01
Size	p. 56-67.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2016.10.031
Database	NAL-Catalogue (AGRICOLA)

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Article: [Significance of extravascular lung water index, pulmonary vascular permeability index, and in- trathoracic blood volume index in the differential diagnosis of burn-induced pulmonary edema].

Lei, Li / Jiajun, Sheng / Guangyi, Wang / Kaiyang, Lyu / Jing, Qin / Gongcheng, Liu / Bing, Ma / Shichu, Xiao / Shihui, Zhu

Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns

2015 Volume 31, Issue 3, Page(s) 186–191

Abstract: Objective: To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema.: ... ...

Abstract	Objective: To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema. Methods: The clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve]. Results: There was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and there was obviously negative correlation between oxygenation index and EVLWI, or oxygenation index and PVPI (with r values respectively -0.674 and -0.817, P values below 0.01). In group H, there was obviously positive correlation between EVLWI and ITBVI (r = 0.751, P < 0.01) but no obvious correlation between EVLWI and PVPI, oxygenation index and EVLWI, or oxygenation index and PVPI (with r values respectively -0.275, 0.197, and 0:062, P values above 0.05). The total area under ROC curve of PVPI value for differentiating the type of pulmonary edema was 0.987 [with 95% confidence interval (CI) 0.962-1.013, P < 0.01], and 1.9 was the cutoff value with sensitivity of 94.1% and specificity of 95.2% . The total area under ROC curve of ITBVI value for differentiating the type of pulmonary edema was 0.940 (with 95% CI 0.860-1.020, P < 0.01), and 1,077. 5 mL/m2 was the cutoff value with sensitivity of 95.2% and specificity of 88.2%. Conclusions: EVLWI, PVPI, and ITBVI have an important significance in the differential diagnosis of the type of burn-induced pulmonary edema, and they may be helpful in the early diagnosis and management of burn-induced pulmonary edema.
MeSH term(s)	Blood Gas Analysis ; Blood Volume ; Burns/complications ; Capillary Permeability ; Diagnosis, Differential ; Extravascular Lung Water ; Humans ; Lung/blood supply ; Lung Injury/physiopathology ; Lung Injury/therapy ; Monitoring, Physiologic ; Pulmonary Edema/diagnosis ; Pulmonary Edema/etiology ; ROC Curve ; Respiration, Artificial ; Retrospective Studies
Language	Chinese
Publishing date	2015-06
Publishing country	China
Document type	English Abstract ; Journal Article
ZDB-ID	2229222-6
ISSN	1009-2587
ISSN	1009-2587
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Article ; Online: Evaluation of dermal substitute in a novel co-transplantation model with autologous epidermal sheet.

Guofeng Huang / Shizhao Ji / Pengfei Luo / Yunqing Zhang / Guangyi Wang / Shihui Zhu / Shichu Xiao / Zhaofan Xia

PLoS ONE, Vol 7, Iss 11, p e

2012 Volume 49448

Abstract: The development of more and more new dermal substitutes requires a reliable and effective animal model to evaluate their safety and efficacy. In this study we constructed a novel animal model using co-transplantation of autologous epidermal sheets with ... ...

Abstract	The development of more and more new dermal substitutes requires a reliable and effective animal model to evaluate their safety and efficacy. In this study we constructed a novel animal model using co-transplantation of autologous epidermal sheets with dermal substitutes to repair full-thickness skin defects. Autologous epidermal sheets were obtained by digesting the basement membrane (BM) and dermal components from rat split-thickness skins in Dispase II solution (1.2 u/ml) at 4 °C for 8, 10 and 12 h. H&E, immunohistochemical and live/dead staining showed that the epidermal sheet preserved an intact epidermis without any BM or dermal components, and a high percentage of viable cells (92.10 ± 4.19%) and P63 positive cells (67.43 ± 4.21%) under an optimized condition. Porcine acellular dermal matrixes were co-transplanted with the autologous epidermal sheets to repair full-thickness skin defects in Sprague-Dawley rats. The epidermal sheets survived and completely re-covered the wounds within 3 weeks. Histological staining showed that the newly formed stratified epidermis attached directly onto the dermal matrix. Inflammatory cell infiltration and vascularization of the dermal matrix were not significantly different from those in the subcutaneous implantation model. Collagen IV and laminin distributed continuously at the epidermis and dermal matrix junction 4 weeks after transplantation. Transmission electron microscopy further confirmed the presence of continuous lamina densa and hemidesmosome structures. This novel animal model can be used not only to observe the biocompatibility of dermal substitutes, but also to evaluate their effects on new epidermis and BM formation. Therefore, it is a simple and reliable model for evaluating the safety and efficacy of dermal substitutes.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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