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BIOMACROMOLECULES · 2025 · IF 5.4

Engineering High-Performance Multifunctional Scaffolds from the Acellular Dermal Matrix for Abdominal Wall Defects Repair via a Dopamine Progressive Permeation-Cross-Linking Strategy

Xinghan Wu,Wenxin Xu,Xuantao Huang,Nianhua Dan,Yining Chen,Zhengjun Li,Yunbing Wang

Emergency repair of complicated full-thickness abdominal wall defects remains one of the most common and challenging surgical emergencies globally. Here, an integrated polydopamine permeating-cross-linking strategy was innovatively proposed to convert porcine acellular dermal matrix (pADM) into versatile, degradation-resistant biopatches (PDA-pADM) for efficiently repairing full-thickness abdominal wall defects. The strategy significantly addresses the challenge that natural-property improvement and biocompatibility of biomaterials are difficult to balance. Molecularly, dopamine (DA) molecules could fully permeate into the collagen fibers of the acellular dermal matrix and then automatically trigger the interfacial in situ polymerization of dopamine monomers among collagen fibers to achieve the efficient cross-linking of pADM. Surprisingly, the enzymatic durability of the biopatch shows significant improvements, extending the original duration from 3 to 20 d. Comprehensive in vivo experiments have shown that PDA-pADM can effectively promote angiogenesis and inhibit inflammatory response, so as to achieve regeneration and repair of abdominal wall damage.

CAS / MDL: 1185-53-1 62-31-7
研究领域: 生物医学工程 · 组织工程 · 外科手术
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Nano Convergence · 2024 ·Vol. 11 ·期 1 ·1-22 · IF 13.4

Designing injectable dermal matrix hydrogel combined with silver nanoparticles for methicillin-resistant Staphylococcus aureus infected wounds healing

Chen Sunfang,Yao Jun,Huo Shicheng,Xu Chennan,Yang Ruting,Tao Danhua,Fang Bin,Ma Gaoxiang,Zhu Zaihua,Zhang Ye,Guo JingJing

Hydrogel-based delivery systems have now emerged as a pivotal platform for addressing chronic tissue defects, leveraging their innate capacity to suppress pathogenic infections and facilitate expedited tissue regeneration. In this work, an injectable hydrogel dressing, termed AgNPs-dermal matrix hydrogel (Ag@ADMH), has been designed to expedite the healing process of wounds afflicted with methicillin-resistant Staphylococcus aureus (MRSA), featuring sustained antibacterial efficacy. The synthesis of the hydrogel dressing entailed a self-assembly process of collagen fibers within an acellular dermal matrix to construct a three-dimensional scaffold, encapsulated with plant polyphenol-functionalized silver nanoparticles (AgNPs). The Ag@ADMH demonstrated exceptional biocompatibility, and enables a sustained release of AgNPs, ensuring prolonged antimicrobial activity. Moreover, the in vitro RT-qPCR analysis revealed that compared with ADMH, Ag@ADMH diminish the expression of iNOS while augmenting CD206 expression, thereby mitigating the inflammatory response and fostering wound healing. Especially, the Ag@ADMH facilitated a reduction in M1 macrophage polarization, as evidenced by a significant decrement in the M1 polarization trend and an enhanced M2/M1 ratio in dermal matrix hydrogels laden with AgNPs, corroborated by confocal microscopy and flow cytometry analyses of macrophage phenotypes. The in vivo assessments indicated that Ag@ADMH minimized fibrous capsule formation. In a full-thickness skin defect model of MRSA infection, the formulation significantly attenuated the inflammatory response by reducing MPO and CD68 expression levels, concurrently promoting collagen synthesis and CD34 expression, pivotal for vasculogenesis, thereby accelerating the resolution of MRSA-infected wounds. These attributes underscore the injectable extracellular matrix hydrogel as a formidable strategy for the remediation and regeneration of infected wounds. Graphical Abstract

研究领域: 生物材料学 · 组织工程 · 再生医学
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Stem Cell Research & Therapy · 2024 ·Vol. 15 ·期 1 ·1-15 · IF 7.1

Adipose-derived stem cells apoptosis rejuvenate radiation-impaired skin in mice via remodeling and rearranging dermal collagens matrix

Zhu Yufan,Liu Xu,Chen Xihang,Liao Yunjun

Background Chronic radiation dermatitis (CRD) is a late consequence of radiation with high incidence in patients receiving radiotherapy. Conventional therapies often yield unsatisfactory results. Therefore, this study aimed to explore the therapeutic potential and mechanism of adipose-derived stem cells (ADSCs) for CRD, paving the way for novel regenerative therapies in clinical practice.Methods Clinical CRD skin biopsies were analyzed to character the pathological changes of CRD skin and guided the animal modeling scheme. Subsequently, an in vivo analysisusing mouse CRD models was conducted to explore their effects of ADSCs on CRD, monitoring therapeutic impact for up to 8 weeks. Transcriptome sequencing and histologic sections analysis were performed to explore the potential therapeutic mechanism of ADSCs. Following observing extensive apoptosis of transplanted ADSCs, the therapeutic effect of ADSCs were compared with those of apoptosis-inhibited ADSCs. Multiphoton imaging and analysis of collagen morphologic features were employed to explain how translated ADSCs promote collagen remodeling at the microscopic level based on the contrast of morphology of collagen fibers.Results Following injection into CRD-afflicted skin, ADSCs therapy effectively mitigated symptoms of CRD, including acanthosis of the epidermis, fibrosis, and irregular collagen deposition, consistent with the possible therapeutic mechanism suggested by transcriptome sequencing. Notably, in vivo tracking revealed a significant reduction in ADSCs number due to extensive apoptosis. Inhibiting apoptosis in ADSCs partially tempered their therapeutic effects. Mechanically, analysis of collagen morphologic features indicated that translated ADSCs might promote dermal extracellular matrix remodeling through enlarging, lengthening, crimping, and evening collagen, counteracting the atrophy and rupture caused by irradiation.Conclusion sThis study demonstrated that ADSCs underwent substantial apoptosis upon local skin transplantation, and paradoxically, this apoptosis is essential for their efficacy in promoting the regeneration of late radiation-impaired skin. Mechanically, transplanted ADSCs could promote the remodeling and rearrangement of radiation-damaged dermal collagen matrix.

研究领域: 再生医学 · 放射生物学 · 干细胞生物学 · 皮肤科
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Fabrication of porcine acellular dermal matrix and oxidized hyaluronic acid conductive composite hydrogels for accelerating skin wound healing under electrical stimulation

Xiaofei Gao,Xinxiang Chai,Yanzhen Lou,Liming Ruan,Zhengfei He,Yunjie Ni,Linggang Sun,Yanfang Sun,Guohua Jiang

Electrical stimulation (ES) of skin wounds can promote cell proliferation, protein synthesis, inflammatory response, and improve neurological function. In this study, the dynamical cross-linked conductive hydrogels have been developed by integration of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) into porcine acellular dermal matrix (PADM) and oxidized hyaluronic acid (OHA) using dopamine-Fe complex (DA@Fe) as cross-linking agent. The as-obtained conductive composite hydrogels have the characteristics of rapid gelation, excellent deformation ability, high water absorption, and suitable degradation rate. Four-point probes resistivity measurement system has been used to test the electrical properties of the as-obtained hydrogels, and showing their conductivity at 0.207–0.322 S/m. In addition, the developed dynamical cross-linked conductive hydrogels exhibit excellent biocompatibility, thereby inducing cells proliferation and migration. In vivo results show that the resultant composite hydrogel can accelerate wound healing with combination of electrical stimulation (ES) by promoting expression of vascular factor (CD31) and decreasing the expression of tumor necrosis factor-α (TNF-α).

研究领域: 生物材料学 · 再生医学 · 组织工程
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FIBERS AND POLYMERS · 2023 ·Vol. 24 ·期 2 ·589-601 · IF 2.5

Electrospun Porcine Acellular Dermal Matrix and Polycaprolactone Composite Nanofibrous Scaffolds for Accelerating Wound Healing

Gao Xiaofei,Jiang Guohua,Ruan Liming,Sun Yanfang,Yunusov Khaydar E.,Jing Yanting,Aharodnikau Uladzislau E.,Solomevich Sergey O.

Electrospun nanofibers represent a novel class of scaffold materials that show great potential in wound healing owing to relatively large surface area, better mimicry of native extracellular matrix, adjustable waterproofness and breathability, and programmable drug delivery process. In this work, electrospun polycaprolactone (PCL) and porcine acellular dermal matrix (PADM) composite nanofibrous membranes have been developed by electrospinning technology and inflated into three-dimensional (3D) structural scaffold (PCL-PADM) by gas foaming method. The obtained PCL-PADM has higher thermal stability, hydrophilicity and better cell adhesion compared with PCL. In addition, ε-polylysine (ε-PL) is further attached onto the surface of PADM/PCL to offer its good antibacterial properties. Moreover, the PADM/PCL fibrous scaffolds show excellent cytocompatibility for promoting cell proliferation. In vivo models showed that the resultant PADM/PCL fibrous scaffolds exhibit an accelerating wound healing effect through promoting expression of vascular factor (CD31) and decreasing the expression of tumor necrosis factor-α (TNF-α). These results indicate that the 3D fibrous scaffolds may be a potential wound dressing for wound closure.

CAS / MDL: 920-66-1
研究领域: 生物材料学 · 组织工程学 · 再生医学
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Materials Today Bio · 2021 · IF 7.348

Construction of multifunctional porcine acellular dermal matrix hydrogel blended with vancomycin for hemorrhage control, antibacterial action, and tissue repair in infected trauma wounds

D. Cai,S. Chen,B. Wu,J. Chen,D. Tao,Z. Li,Q. Dong,Y. Zou,Y. Chen,C. Bi,D. Zu,L. Lu,B. Fang

Prevention of bacterial infection and reduction of hemorrhage, the primary challenges posed by trauma before hospitalization, are essential steps in prolonging the patient's life until they have been transported to a trauma center. Extracellular matrix (ECM) hydrogel is a promising biocompatible material for accelerating wound closure. However, due to the lack of antibacterial properties, this hydrogel is difficult to be applied to acute contaminated wounds. This study formulates an injectable dermal extracellular matrix hydrogel (porcine acellular dermal matrix (ADM)) as a scaffold for skin defect repair. The hydrogel combines vancomycin, an antimicrobial agent for inducing hemostasis, expediting antimicrobial activity, and promoting tissue repair. The hydrogel possesses a porous structure beneficial for the adsorption of vancomycin. The antimicrobial agent can be timely released from the hydrogel within an hour, which is less than the time taken by bacteria to infest an injury, with a cumulative release rate of approximately 80%, and thus enables a relatively fast bactericidal effect. The cytotoxicity investigation demonstrates the biocompatibility of the ADM hydrogel. Dynamic coagulation experiments reveal accelerated blood coagulation by the hydrogel. In vivo antibacterial and hemostatic experiments on a rat model indicate the healing of infected tissue and effective control of hemorrhaging by the hydrogel. Therefore, the vancomycin-loaded ADM hydrogel will be a viable biomaterial for controlling hemorrhage and preventing bacterial infections in trauma patients.

CAS / MDL: 1404-90-6
研究领域: 生物医学工程 · 伤口愈合 · 组织工程 · 药剂学
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Collagen and Leather · 2024 ·Vol. 6 ·期 1 ·1-13 · IF 0

Development of mADM-collagen wound dressings for mimicking native skin architecture to enhance skin wound healing

Wang Xiang,Jiang Yujia,Sun Xiaoqin,Yue Chongxia,Li Zhengyong,Wu Yao

Acellular dermal matrix (ADM) is one of the most promising scaffold materials due to its ability to retain natural extracellular matrix structure. Micronized acellular dermal matrix (mADM) was prepared with no intact cell nuclei and preserved growth factors by High Hydrostatic Pressure (HHP) approach. And mADM-collagen wound dressings were developed with different proportion of type I collagen and recombinant humanized type III collagen. The porous structure of the mADM-collagen wound dressings made them a good candidate for preventing excessive fluid accumulation, while the collagens with gel-like texture combined with mADM powder to form pasty texture wound dressing, which preserving the moisture at the wound site. Moreover, the paste texture of the mADM-collagen wound dressing was easy to reshape to conform any wound shapes and body contours. Furthermore, the resulted mADM-collagen wound dressings showed good biocompatibility by supporting fibroblasts adhesion and proliferation in vitro. Subsequently, a murine model of full-thickness skin wounds was employed to assess its effects on wound healing. Notably, mADM-75% Col-I exhibited superior effects throughout the wound healing process, specifically it promoted neovascularization, skin appendage growth and new skin regeneration. This formulation closely mimicked the collagen ratio found in healthy skin, facilitating the favorable wound repair. These results indicated the superior performance of this mADM-collagen wound dressing providing an optimal environment for wound healing. Graphical Abstract

研究领域: 生物材料 · 组织工程 · 创伤修复
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EUROPEAN JOURNAL OF MEDICAL RESEARCH · 2019 ·Vol. 24 ·期 1 ·1-9 · IF 1.736

Human umbilical cord mesenchymal stem cells implantation accelerates cutaneous wound healing in diabetic rats via the Wnt signaling pathway

Han Yanfu,Sun Tianjun,Han Yanqing,Lin Lingling,Liu Chang,Liu Jing,Yan Guangzhi,Tao Ran

ObjectiveDifficulty in wound healing is one common complication of diabetes mellitus. The study explored whether the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic ulcer wound was enhanced by the activation of the Wnt signaling pathway.Methods Rat diabetic model was established by intraperitoneal injection of Streptozotocin (STZ). hUCMSCs were purified and seeded on the collagen–chitosan laser drilling acellular dermal matrix (CCLDADM) scaffold, which was subsequently implanted into the cutaneous wound of normal and diabetic rats, followed by daily injection of Wnt signaling pathway agonist (Wnt3a) or antagonist (sFRP3) at the edge of the scaffold. Wound healing was checked on days 7, 14, and 21, and the fibrous tissue deposition, capillaries, and epidermal regeneration at the wound were examined by hematoxylin–eosin staining. The hUCMSCs-CCLDADM scaffold was cultured in vitro and treated with Wnt3a or sFRP3, followed by evaluation of cell proliferation, cell proliferation rate, survival status, and altered protein levels in the Wnt signaling pathway using BrdU staining, CCK-8 assay, live/dead staining, and Western blotting, respectively.Results On days 7 and 14 postoperatively, the speed of wound healing was significantly lower in diabetic rats than that in normal control rats. This phenomenon was significantly improved by the activation of the Wnt signaling pathway that also elevated the fibrous protein deposition and the abundance of capillary in the granulation tissue. Conversely, blockade of Wnt signaling slowed the healing of skin wound in diabetic rats. The activation of Wnt signaling pathway promoted the proliferation and differentiation and decreased the apoptosis of hUCMSCs, thereby elevating the number of living hUCMSCs on the CCLDADM scaffold, while the suppression exerted a contrary effect.Conclusion The activation of the Wnt signaling pathway promotes the healing of diabetic skin wound by the regulation of proliferation and differentiation of hUCMSCs on the CCLDADM scaffold.

CAS / MDL: 18883-66-4
研究领域: 干细胞生物学 · 糖尿病研究 · 分子信号通路 · 再生医学
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Biomaterials Advances · 2022 · IF 0

Polydopamine modified acellular dermal matrix sponge scaffold loaded with a-FGF: Promoting wound healing of autologous skin grafts

Lianglong Chen,Jun Ma,Yujia Chen,Chaoyang Huang,Zijun Zheng,Yanbin Gao,Ziwei Jiang,Xuerong Wei,Yujie Peng,Shengxiang Yu,Lei Yang

Despite increasing potentials as a skin regeneration template (DRT) to guide tissue healing, acellular dermal matrix (ADM) is still challenged by issues (like dense architecture, low cellular adhesion and poor vascularization), contributing to necrosis and shedding of upper transplanted skins. Modified with polydopamine (PDA), a novel and porous DRT capable of drug delivery was designed using porcine-derived ADM (PADMS) gels, termed PDA-PADMS. However, it was unclear whether it could efficiently deliver human acidic fibroblast growth factor (a-FGF) and regenerate skin defects. Herein, after being fabricated and optimized with PADMS gels in different ratios (1:6, 1:7, 1:8), PDA-PADMS loading a-FGF (PDA-PADMS-FGF) was evaluated by the morphology, physical& chemical properties, drug release and in-vitro biological evaluations, followed by full-thickness skin defects implanted with PDA-PADMS-FGF covered by transplanted skins. Apart from containing abundant collagen and elastin, porous PADMS (with a loose and uniform structure) was demonstrated to possess controlled release of a-FGF and biocompatibility attributed to PDA coating. Consistent with augmented cellular migration and proliferation in vitro, PDA-PADMS-FGF also accelerated wound healing and reduced scarring, improving collagen arrangement and neovascularization. In conclusion, PDA-PADMS-FGF has a good potential and application prospect as a matrix material for wound repair.

研究领域: 组织工程 · 伤口愈合 · 生物医用材料 · 药物递送系统 · 再生医学
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iScience · 2022 · IF 6.107

Multifunctional sponge scaffold loaded with concentrated growth factors for promoting wound healing

Lianglong Chen,Chaoyang Huang,Yu Zhong,Yujia Chen,Huihui Zhang,Zijun Zheng,Ziwei Jiang,Xuerong Wei,Yujie Peng,Lei Huang,Libin Niu,Yanbin Gao,Jun Ma,Lei Yang

Summary Although both are applied in regenerative medicine, acellular dermal matrix (ADM) and concentrated growth factor (CGF) have their respective shortcoming: The functioning of CGF is often hindered by sudden release effects, among other problems, and ADM can only be used in outer dressing for wound healing. In this study, a compound network with physical-chemical double cross-linking was constructed using chemical cross-linking and the intertwining of ADM and chitosan chains under freezing conditions; equipped with good biocompatibility and cell/tissue affinity, the heparin-modified composite scaffold was able to significantly promote cell adhesion and proliferation to achieve adequate fixation and slow down the release of CGF; polydopamine nanoparticles having excellent near-infrared light photothermal conversion ability could significantly promote the survival of rat autologous skin grafts. In a word, this multifunctional composite scaffold is a promising new type of implant biomaterial capable of delivering CGF to promote the healing of full-thickness skin defects.

CAS / MDL: 64-19-7 30525-89-4
研究领域: 再生医学 · 生物材料 · 组织工程 · 伤口愈合
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

A dual-modified glucomannan polysaccharide selectively sequesters growth factors for skin tissue repair

Xiaotong Hu,Daping Xie,Yuwei Li,Yiming Niu,Rongwei Tan,Zhending She,Chunming Wang

Artificial dermal matrixes (ADMs) are valuable clinical options for treating large soft tissue defects, but their suboptimal bioactivities compared with the real tissue limit their therapeutic potential. For example, glycosaminoglycan (GAG) polysaccharides in the native skin vitally and differentially regulate endogenous growth factors (GFs) to maintain tissue homeostasis. However, the GAG used in the current ADMs has often lost such delicate regulation. Here, we developed a novel polysaccharide-based ADM that can promote skin tissue repair through selective modulation of specific pro-healing GFs. First, we prepared a plant-derived backbone of glucomannan (named BSP) – representing the two dominant monosaccharide components in the human body – in mass and homogenic quality. Then, we modified this backbone with sulfate and acetyl groups in a controlled manner to yield an optimized BSP derivative (S M A L -BSP) as a main composition to generate a new ADM. In vitro, S M A L -BSP enabled the ADM to selectively sequester pro-angiogenic GFs of VEGF-A and FGF-2 in situ for stimulating endothelial cell growth. Moreover, the addition of the acetyl group induced macrophages to secrete nitric oxide (NO) with antibacterial activities. Further in vivo tests in a rat model of full-thickness skin wounds indicated that S M A L -BSP ADM could sequester GFs in situ to promote angiogenesis and thus tissue regeneration, with superior effects than conventional chondroitin sulfate-based ADM, while showing no adverse effects often associated with animal-derived products. Our study represents a novel strategy for ADM design, targeting selective GF sequestration towards optimal skin tissue regeneration.

研究领域: 组织工程 · 生物材料 · 伤口愈合 · 药剂学
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