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Reversibly immortalized keratinocytes(iKera)facilitate re-epithelization and skin wound healing:Potential applications in cell-based skin tissue engineering

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Bioactive Materials 2022年第3期7卷 523-540页

作者： Jiamin Zhong Hao Wang Ke Yang Huifeng Wang Chongwen Duan Na Ni Liqin An Yetao Luo Piao Zhao Yannian Gou Shiyan Sheng Deyao Shi Connie Chen William Wagstaff b Bryce Hendren-Santiago b Rex C.Haydon b Hue H.Luu b Russell R.Reid Sherwin HHo Guillermo A.Ameer Le Shen Tong-Chuan He Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistrySchool of Laboratory MedicineChongqing Medical UniversityChongqing400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL60637USA The Pediatric Research Institute The Children’s Hospital of Chongqing Medical UniversityChongqing400014China Biomedical engineering Department Northwestern UniversityEvanstonIL60208USA Department of Orthopaedics Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Surgery The University of Chicago Medical CenterChicagoIL60637USA Center for Advanced Regenerative engineering(CARE) EvanstonIL60208USA Department of Surgery Northwestern University Feinberg School of MedicineChicagoIL60616USA

skin injury is repaired through a multi-phase wound healing process of tissue granulation and *** failure in the healing process may lead to chronic non-healing wounds or abnormal scar *** significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical *** are critical to re-epithelialization and wound ***,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound *** first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were *** a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound ***,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.

关键词： Keratinocytes skin tissue engineering Reversible immortalization SV40 large T antigen PPCN skin wound healing

skin tissue engineering advances in severe burns:review and therapeutic applications

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Burns & Trauma 2016年第1期4卷 13-26页

作者： Alvin Wen Choong Chua Yik Cheong Khoo Bien Keem Tan Kok Chai Tan Chee Liam Foo Si Jack Chong Singapore General Hospital Department of PlasticReconstructive andAesthetic Surgery20 College RoadAcademia Level 4Singapore 169845Singapore. Singapore General Hospital Skin Bank UnitBlock 4 Level 3Room 15Outram RoadSingapore 169608Singapore. Transplant tissueCentre c/o Skin Bank UnitSingapore General HospitalBlock 4 Level 3 RoomA7Outram RoadSingapore 169608Singapore. Singapore General Hospital Skin Bank UnitBlock 4 Level 3Room 15Outram RoadSingapore 169608Singapore. Transplant tissueCentre c/o Skin Bank UnitSingapore General HospitalBlock 4 Level 3 RoomA7Outram RoadSingapore 169608Singapore. Singapore General Hospital Department of PlasticReconstructive andAesthetic Surgery20 College RoadAcademia Level 4Singapore 169845Singapore. Singapore General Hospital Skin Bank UnitBlock 4 Level 3Room 15Outram RoadSingapore 169608Singapore.

Current advances in basic stem cell research and tissue engineering augur well for the development of improved cultured skin tissue substitutes:a class of products that is still fraught with limitations for clinical *** the ability to grow autologous keratinocytes in-vitro from a small skin biopsy into sheets of stratified epithelium(within 3 to 4 weeks)helped alleviate the problem of insufficient donor site for extensive burn,many burn units still have to grapple with insufficient skin allografts which are used as intermediate wound coverage after burn *** offered by tissue-engineered skin dermal replacements to meet emergency demand have been used fairly *** the availability of these commercial products,they all suffer from the same problems of extremely high cost,sub-normal skin microstructure and inconsistent engraftment,especially in full thickness *** practice for severe burn treatment has since evolved to incorporate these tissue-engineered skin substitutes,usually as an adjunct to speed up epithelization for wound closure and/or to improve quality of life by improving the functional and cosmetic results *** review seeks to bring the reader through the beginnings of skin tissue engineering,the utilization of some of the key products developed for the treatment of severe burns and the hope of harnessing stem cells to improve on current practice.

关键词： Burns skin tissue engineering Stem cells Cultured epithelial autografts Dermal substitutes Microskin grafting

Antibacterial Electrospun Nanofibrous Materials for Wound Healing

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Advanced Fiber Materials 2023年第1期5卷 107-129页

作者： Zijian Wang Weikang Hu Wang Wang Yu Xiao Yun Chen Xinghuan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biomedical engineering and Hubei Province Key Laboratory of Allergy and Immune Related Disease TaiKang Medical School(School of Basic Medicine Sciences)Wuhan UniversityWuhan 430071China Ministry of Education Key Laboratory of the Green Preparation and Application for Functional Materials Hubei Key Laboratory of Polymer MaterialsSchool of Materials Science and EngineeringHubei UniversityWuhan 430062China

One of the leading causes of wound healing delays is bacterial infection,which limits the process of restoring the histological and functional integrity of the *** nanofibrous materials(ENMs)are biocompatible and biodegradable,and they can provide specific physical,chemical,and biological cues to accelerate wound *** on this fact,a series of multifunctional ENMs for complex clinical applications,particularly infected skin injuries,have been ***-biotics,antimicrobial peptides(AMPs),metals and metal oxides(MMOs),and antibacterial polymers have previously been incorporated into ENMs through advanced material processing techniques,endowing ENMs with enhanced and excellent antibacterial *** review summarizes wound healing issues and provides recent advances in antibacterial ENMs created by cutting-edge *** future of clinical and translational research on ENMs is also discussed.

关键词： Electrospinning Nanofiber Wound dressing Antibacterial activity skin tissue engineering

Mechanical performance and cyocompatibility of PU/PLCL nanofibrous electrospun scaffolds for skin regeneration

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Engineered Regeneration 2022年第1期3卷 53-58页

作者： Xiang Gao Meiling Wen Yang Liu Tian Hou Meiwen An Institute of Biomedical engineering College of Biomedical EngineeringTaiyuan University of TechnologyShanxi Key Laboratory of Material Strength&Structural ImpactTaiyuanShanxi030024China Research Center for Nano-Biomaterials&Regenerative Medicine Department of Biomedical EngineeringCollege of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan 030024China

skin tissue engineering with considerable skin regeneration capability is an urgent need for the wound *** current challenge for researchers is to develop a bionic scaffold that imitates the extracellular matrix for the regeneration of the damaged *** our study,poly(L-lactide-co-caprolactone)(PLCL)was blended with polyurethane(PU)to obtain nanofibrous scaffolds via *** electrospun fibers with 50%PLCL content had a certain number of intersections and jointing points,and exhibited significantly enhanced mechani-cal properties combined with suitable ***,cell activities demonstrated that PU/PLCL membranes had significantly biological advantages in enhanced growth of human skin fibroblasts with spreading morphology compared with PU membranes,indicating good cytocompatibility of composite *** findings proved that PU/PLCL electrospun membranes have great potential in applications of skin tissue engineering.

关键词： Electrospun membranes Poly(L-lactide-co-caprolactone) Polyurethane Human skin fibroblasts skin tissue engineering

Antibacterial biomaterials for skin wound dressing

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Asian Journal of Pharmaceutical Sciences 2022年第3期17卷 353-384页

作者： Yuqing Liang Yongping Liang Hualei Zhang Baolin Guo Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710049China State Key Laboratory for Mechanical Behavior of Materials and Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an 710049China

Bacterial infection and the ever-increasing bacterial resistance have imposed severe threat to human *** bacterial contamination could significantly menace the wound healing *** the sophisticated wound healing process,novel strategies for skin tissue engineering are focused on the integration of bioactive ingredients,antibacterial agents included,into biomaterials with different morphologies to improve cell behaviors and promote wound ***,a comprehensive review on antibacterial wound dressing to enhance wound healing has not been *** this review,various antibacterial biomaterials as wound dressings will be *** kinds of antibacterial agents,including antibiotics,nanoparticles(metal and metallic oxides,lightinduced antibacterial agents),cationic organic agents,and others,and their recent advances are *** selection and fabrication of biomaterials with different structures and forms,including films,hydrogel,electrospun nanofibers,sponge,foam and three-dimension(3D)printed scaffold for skin regeneration,are elaborated *** challenges and the future perspectives are presented in thismultidisciplinary *** envision that this review will provide a general insight to the elegant design and further refinement of wound dressing.

关键词： Antibacterial activity Wound healing Wound dressing skin tissue engineering Biomaterials

Engineered artificial skins:Current construction strategies and applications

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Engineered Regeneration 2023年第4期4卷 438-450页

作者： Ye Xu Xiangyi Wu Yuanyuan Zhang Yunru Yu Jingjing Gan Qian Tan Department of Burn and Plastic Surgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingChina Pharmaceutical Sciences Laboratory Åbo Akademi UniversityTurku 20520Finland

skin damage resulting from burns,injuries,or diseases can lead to significant functional and esthetic ***,traditional treatments,such as skin grafting,have limitations including limited donor skin availability,poor aesthetics,and functional *** tissue engineering provides a promising alternative,with engineered artificial skins offering a highly viable *** artificial skin is designed to mimic or replace the functions of natural human skin and find applications in various medical treatments,particularly for severe burns,chronic wounds,and other skin injuries or *** artificial skins aim to promote wound healing,provide temporary coverage,permanent skin replacement,and restore the skin’s barrier *** skins have diverse applications in medicine and wound care,addressing burns,chronic wounds,and traumatic *** also serve as valuable tools for research in tissue engineering,offering experimental models for studying wound healing mechanisms,testing new biomaterials,and exploring innovative approaches to skin *** review provides an overview of current construction strategies for engineered artificial skin,including cell sources,biomaterials,and construction *** further explores the primary application areas and future prospects of artificial skin,highlighting their potential to revolutionize skin reconstruction and advance the field of regenerative medicine.

关键词： Artificial skin skin tissue engineering Biomaterial Cell scaffold Wound healing

Fabrication of SA/Gel/C scaffold with 3D bioprinting to generate micro-nano porosity structure for skin wound healing: a detailed animal in vivo study

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Cell Regeneration 2022年第1期11卷 97-108页

作者： Changmei Niu Liyang Wang Dongdong Ji Mingjun Ren Dongxu Ke Qiang Fu Kaile Zhang Xi Yang Novaprint Therapeutics Suzhou Co. LtdSuzhou 215000China Shanghai University of engineering Science Shanghai 201620China Department of Burns and Plastic Surgery Affiliated Suzhou Hospital Of Nanjing Medical University Suzhou 215000China State Key Laboratory of Mechanical System and Vibration School of Mechanical EngineeringShanghai Jiaotong UniversityShanghai 200240China The Department of Urology Affiliated Sixth People’s HospitalShanghai JiaoTong UniversityShanghai 200235China Shanghai Eastern Institute of Urologic Reconstruction Shanghai 200000China

Bioprinting has exhibited remarkable promises for the fabrication of functional skin ***,there are some significant challenges for the treatment of full-thickness skin defects in clinical *** is necessary to determine bioinks with suitable mechanical properties and desirable ***,the key for printing skin is to design the skin structure optimally,enabling the function of the *** this study,the full-thickness skin scaffolds were prepared with a gradient pore structure constructing the dense layer,epidermis,and dermis by different ratios of *** hypothesized that the dense layer protects the wound surface and maintains a moist environment on the wound *** developing a suitable hydrogel bioink formulation(sodium alginate/gelatin/collagen),to simulate the physiological structure of the skin via 3D printing,the proportion of hydrogels was optimized corresponding to each *** results reveal that the scaffold has interconnected macroscopic channels,and sodium alginate/gelatin/collagen scaffolds accelerated wound healing,reduced skin wound contraction,and re-epithelialization in *** is expected to provide a rapid and economical production method of skin scaffolds for future clinical applications.

关键词： 3D bioprinting skin tissue engineering skin scaffold Hydrogel

Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing

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Regenerative Biomaterials 2021年第5期8卷 75-86页

作者： Alessia Ajovalasit Carlos Redondo-Go´mez Maria Antonietta Sabatino Babatunde OOkesola Kristin Braun Alvaro Mata Clelia Dispenza Dipartimento di Ingegneria(DI) Universitadegli Studi di PalermoViale delle ScienzeEdificio 6Palermo 90128Italy School of engineering&Materials Science Queen Mary University of LondonLondon E14NSUK Institute of Bioengineering Queen Mary University of LondonLondon E14NSUK Blizard Institute Barts and The London School of Medicine and DentistryThe Blizard Building4 Newark StreetLondon E12ATUK School of Pharmacy University of NottinghamNottingham NG72RDUK Department of Chemical and Environmental engineering University of NottinghamNottingham NG72RDUK Biodiscovery Institute University of NottinghamNottinghamNG72RDUK Istituto di Biofisica(IBF) Consiglio Nazionale Delle Ricerche(CNR)Via U.La Malfa 153Palermo 90146Italy

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound *** work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular *** this aim,the co-assembly behaviour of a carboxylated variant of xyloglucan(CXG)with a peptide amphiphile(PA-H3)has been investigated to generate hierarchical constructs with tuneable molecular composition,structure,and *** electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and *** a higher concentration,CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by smallamplitude oscillatory shear rheological measurements and compression tests at different CXG/PAH3 ratios.A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model.

关键词： self-assembly peptide nanofiber hydrogel wound healing skin tissue engineering

维生素C功能化丝素蛋白纳米纤维的制备和表征

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维生素C功能化丝素蛋白纳米纤维的制备和表征

作者：范林鹏东华大学

学位级别：硕士

维生素C是一种重要的生物活性因子,具有许多重要的生理功能。除了人类以外,几乎所有的动物都能合成维生素C。目前,维生素C作为护肤品中的生物活性因子已经引起了广泛的关注。研究证明,维生素C在抗氧化过程中起着重要的作用,它能去除和... 详细信息

维生素C是一种重要的生物活性因子,具有许多重要的生理功能。除了人类以外,几乎所有的动物都能合成维生素C。目前,维生素C作为护肤品中的生物活性因子已经引起了广泛的关注。研究证明,维生素C在抗氧化过程中起着重要的作用,它能去除和淬灭自由基。作为一种抗氧化剂,维生素C还能保护皮肤免受紫外线伤害、光敏反应、光老化以及皮肤癌等。然而,维生素C遇到光、潮湿和氧等很不稳定。此外,许多生物活性因子包括维生素C很难穿透皮肤角质层。因此,为了更有效地递送维生素C以充分发挥它的功能为皮肤所用,有必要开发一些稳定的维生素C衍生物和先进的载体。丝素蛋白是家蚕丝的主要成份,它是一种天然高分子蛋白。最近,丝素蛋白以其优异的生物学性能,比如好的透氧透气性、良好的生物相容性和生物可降解性、低免疫原性、独特的力学性能等引起了广泛研究者的兴趣。此外,丝素蛋白还能帮助皮肤保持水份、保护皮肤免于紫外线伤害以及去除皮肤黑色素等。实际上,丝素蛋白已经作为常用的添加剂,广泛应用到食品、医药以及护肤品等行业中。静电纺丝技术是一种制备纳米纤维简单而有效的方法,静电纺纳米纤维以其孔隙率高、比表面积大等独特的性能已被广泛应用到各个领域。近年来,静电纺丝素蛋白纳米纤维模拟细胞外基质引起了越来越多的关注。我们目前的工作发展了一种简单、安全、有效的即来自静电纺丝素蛋白水溶液的纳米纤维以75%的乙醇蒸汽处理,它将丝素蛋白的后处理和灭菌过程巧妙地结合在一起。核磁共振和X-衍射分析证实,这种后处理成功地将丝素蛋白纳米纤维基质的结构从SilkⅠ转变为SilkⅡ。生物学分析表明这样制备的丝素蛋白纳米纤维基质有利于细胞的生长。这种巧妙的处理方式对于设计和制备各种各样的载药纳米纤维为组织工程所用是非常有意义的。借助于以上绿色制备工艺,我们成功制备了维生素C/丝素蛋白复合纳米纤维。扫描电镜分析显示维生素C的加入有利于在低浓度下静电纺丝素蛋白水溶液。同时,核磁共振和X-衍射分析表明维生素C的加入并没有影响丝素蛋白纳米纤维基质的结构,经过75%的乙醇蒸汽处理,复合纳米纤维的结构从SilkⅠ转变为SilkⅡ。这样负载维生素C的丝素蛋白纳米纤维基质展现了较快的维生素释放行为,这可能对于复合纳米纤维基质作为治疗介质和护肤品是非常有意义的。实时荧光定量PCR结果表明,丝素蛋白纳米纤维在一定程度上能促进细胞超氧化物歧化酶的表达,而维生素C/丝素蛋白复合纳米纤维基质则能明显促进细胞谷胱甘肽过氧化物酶的表达,这对于复合纳米纤维在组织工程中的应用是非常有意义的。因此,负载维生素C的丝素蛋白纳米纤维基质能更有效地递送维生素C到皮肤组织以满足外用的需要,因为复合纳米纤维不仅整合了丝素蛋白和维生素C的优势,它还具有纳米纤维的独特性能。

关键词： silk fibroin Vitamin C electrospinning green processing novel skin-care product skin tissue engineering