Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex s...Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.展开更多
In a general wound healing process, foreign bodies and tissue detritus have to be broken down and then a new tissue is produced. However, the new tissue formation sometimes fails to proceed under the impaired conditio...In a general wound healing process, foreign bodies and tissue detritus have to be broken down and then a new tissue is produced. However, the new tissue formation sometimes fails to proceed under the impaired conditions such as burn injury and intractable skin ulcer. A major obstruction to wound healing is infection. Another obstruction to wound healing is deficiency of growth factors. The endogenous levels of growth factors are reduced in some chronic wounds. To improve these wound conditions, researchers have been trying to create several types of artificial skins. The tissue-engineered products include three prime constituents, i.e., cells, growth factors, and materials. In this review, the practical design of tissue-engineered products for skin regenerative medicine is introduced. The first design makes it possible to release silver sulfadiazine (AgSD) from a wound dressing. The second design makes it possible to release Epidermal Growth Factor (EGF) from a wound dressing or a skin care product composed of hyaluronic acid spongy sheet containing bioactive ingredients. The third design makes it possible to release several types of growth factors from allogeneic fibroblasts within cultured dermal substitute. This tissue-engineered product is prepared by seeding allogeneic fibroblasts into a collagen and hyaluronic acid spongy sheet. Although allogeneic cells are rejected gradually in immune system, they are able to release some types of growth factors, thereby regenerating a damaged tissue. The clinical study demonstrates that these tissue-engineered products are promising for the treatment of burn injury and intractable skin ulcer.展开更多
Angiogenesis is a key process in regenerative medicine generally, as well as in the specific field of nerve regeneration. However, no convenient and objective method for evaluating the angiogenesis of tissue-engineere...Angiogenesis is a key process in regenerative medicine generally, as well as in the specific field of nerve regeneration. However, no convenient and objective method for evaluating the angiogenesis of tissue-engineered nerves has been reported. In this study, tissue-engineered nerves were constructed in vitro using Schwann cells differentiated from rat skin-derived precursors as supporting cells and chitosan nerve conduits combined with silk fibroin fibers as scaffolds to bridge 10-mm sciatic nerve defects in rats. Four weeks after surgery, three-dimensional blood vessel reconstructions were made through MICROFIL perfusion and micro-CT scanning, and parameter analysis of the tissue-engineered nerves was performed. New blood vessels grew into the tissue-engineered nerves from three main directions： the proximal end, the distal end, and the middle. The parameter analysis of the three-dimensional blood vessel images yielded several parameters, including the number, diameter, connection, and spatial distribution of blood vessels. The new blood vessels were mainly capillaries and microvessels, with diameters ranging from 9 to 301 μm. The blood vessels with diameters from 27 to 155 μm accounted for 82.84% of the new vessels. The microvessels in the tissue-engineered nerves implanted in vivo were relatively well-identified using the MICROFIL perfusion and micro-CT scanning method, which allows the evaluation and comparison of differences and changes of angiogenesis in tissue-engineered nerves implanted in vivo.展开更多
Tissue engineering essentially refers to technology for growing new human tissue and is distinct from regenerative medicine. Currently, pieces of skin are already being fabricated for clinical use and many other tissu...Tissue engineering essentially refers to technology for growing new human tissue and is distinct from regenerative medicine. Currently, pieces of skin are already being fabricated for clinical use and many other tissue types may be fabricated in the future.Tissue engineering was first defined in 1987 by the United States National Science Foundation which critically discussed the future targets of bioengineering research and its consequences. The principles of tissue engineering are to initiate cell cultures in vitro, grow them on scaffolds in situ and transplant the composite into a recipient in vivo. From the beginning, scaffolds have been necessary in tissue engineering applications. Regardless, the latest technology has redirected established approaches by omitting scaffolds. Currently, scientists from diverse research institutes are engineering skin without scaffolds. Due to their advantageous properties, stem cells have robustly transformed the tissue engineering field as part of an engineered bilayered skin substitute that will later be discussed in detail. Additionally, utilizing biomaterials or skin replacement products in skin tissue engineering as strategy to successfully direct cell proliferation and differentiation as well as to optimize the safety of handling during grafting is beneficial. This approach has also led to the cells' application in developing the novel skin substitute that will be briefly explained in this review.展开更多
Derma is progenitor cells sours, that are able to differentiate further in several mesodermal lineage and neural and endodermal lineage. Culture conditions, skin taking site and culture medium composition considerably...Derma is progenitor cells sours, that are able to differentiate further in several mesodermal lineage and neural and endodermal lineage. Culture conditions, skin taking site and culture medium composition considerably contribute to it. Spheroid cultured mesenchymal dermal cells contribution to skin regeneration in granulating wound in rat model was estimated.展开更多
Background:The aim of this in vitro study was to compare side-by-side two models of human bilayered tissue-engineered skin substitutes(hbTESSs)designed for the treatment of severely burned patients.These are the scaff...Background:The aim of this in vitro study was to compare side-by-side two models of human bilayered tissue-engineered skin substitutes(hbTESSs)designed for the treatment of severely burned patients.These are the scaffold-free self-assembled skin substitute(SASS)and the human plasma-based skin substitute(HPSS).Methods:Fibroblasts and keratinocytes from three humans were extracted from skin biopsies(N=3)and cells from the same donor were used to produce both hbTESS models.For SASS manu-facture,keratinocytes were seeded over three self-assembled dermal sheets comprising fibroblasts and the extracellular matrix they produced(n=12),while for HPSS production,keratinocytes were cultured over hydrogels composed of fibroblasts embedded in either plasma as unique biomaterial(Fibrin),plasma combined with hyaluronic acid(Fibrin-HA)or plasma combined with collagen(Fibrin-Col)(n/biomaterial=9).The production time was 46-55 days for SASSs and 32-39 days for HPSSs.Substitutes were characterized by histology,mechanical testing,PrestoBlue™-assay,immunofluorescence(Ki67,Keratin(K)10,K15,K19,Loricrin,type IV collagen)and Western blot(type I and IV collagens).Results:The SASSs were more resistant to tensile forces(p-value<0.01)but less elastic(p-value<0.001)compared to HPSSs.A higher number of proliferative Ki67+cells were found in SASSs although their metabolic activity was lower.After epidermal differentiation,no significant difference was observed in the expression of K10,K15,K19 and Loricrin.Overall,the production of type I and type IV collagens and the adhesive strength of the dermal-epidermal junction was higher in SASSs.Conclusions:This study demonstrates,for the first time,that both hbTESS models present similar in vitro biological characteristics.However,mechanical properties differ and future in vivo experiments will aim to compare their wound healing potential.展开更多
Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs(ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior a...Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs(ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering.The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.展开更多
Craniomaxillofacial(CMF)reconstruction is a challenging clinical dilemma.It often necessitates skin replacement in the form of autologous graft or flap surgery,which differ from one another based on hypodermal/dermal ...Craniomaxillofacial(CMF)reconstruction is a challenging clinical dilemma.It often necessitates skin replacement in the form of autologous graft or flap surgery,which differ from one another based on hypodermal/dermal content.Unfortunately,both approaches are plagued by scarring,poor cosmesis,inadequate restoration of native anatomy and hair,alopecia,donor site morbidity,and potential for failure.Therefore,new reconstructive approaches are warranted,and tissue engineered skin represents an exciting alternative.In this study,we demonstrated the reconstruction of CMF full-thickness skin defects using intraoperative bioprinting(IOB),which enabled the repair of defects via direct bioprinting of multiple layers of skin on immunodeficient rats in a surgical setting.Using a newly formulated patient-sourced allogenic bioink consisting of both human adipose-derived extracellular matrix(adECM)and stem cells(ADSCs),skin loss was reconstructed by precise deposition of the hypodermal and dermal components under three different sets of animal studies.adECM,even at a very low concentration such as 2%or less,has shown to be bioprintable via droplet-based bioprinting and exhibited de novo adipogenic capabilities both in vitro and in vivo.Our findings demonstrate that the combinatorial delivery of adECM and ADSCs facilitated the reconstruction of three full-thickness skin defects,accomplishing near-complete wound closure within two weeks.More importantly,both hypodermal adipogenesis and downgrowth of hair follicle-like structures were achieved in this two-week time frame.Our approach illustrates the translational potential of using human-derived materials and IOB technologies for full-thickness skin loss.展开更多
Meniscus is a wedge-shaped fibrocartilaginous tissue,playing important roles in maintaining joint stability and function.Meniscus injuries are difficult to heal and frequently progress into structural breakdown,which ...Meniscus is a wedge-shaped fibrocartilaginous tissue,playing important roles in maintaining joint stability and function.Meniscus injuries are difficult to heal and frequently progress into structural breakdown,which then leads to osteoarthritis.Regeneration of heterogeneous tissue engineering meniscus(TEM)continues to be a scientific and translational challenge.The morphology,tissue architecture,mechanical strength,and functional applications of the cultivated TEMs have not been able to meet clinical needs,which may due to the negligent attention on the importance of microenvironment in vitro and in vivo.Herein,we combined the 3D(three-dimensional)-printed gradient porous scaffolds,spatiotemporal partition release of growth factors,and anti-inflammatory and anti-oxidant microenvironment regulation of Ac2-26 peptide to prepare a versatile meniscus composite scaffold with heterogeneous bionic structures,excellent biomechanical properties and anti-inflammatory and anti-oxidant effects.By observing the results of cell activity and differentiation,and biomechanics under anti-inflammatory and anti-oxidant microenvironments in vitro,we explored the effects of anti-inflammatory and anti-oxidant microenvironments on construction of regional and functional heterogeneous TEM via the growth process regulation,with a view to cultivating a high-quality of TEM from bench to bedside.展开更多
Objective. To explore a feasible method to repair full-thickness skin defects utilizing tissue engineered techniques. Methods： The Changfeng hybrid swines were used and the skin specimens were cut from the posterior...Objective. To explore a feasible method to repair full-thickness skin defects utilizing tissue engineered techniques. Methods： The Changfeng hybrid swines were used and the skin specimens were cut from the posterior limb girdle region, from which the keratinocytes and fibroblasts were isolated and harvested by trypsin, EDTA, and type II collagenase. The cells were seeded in Petri dishes for primary culture. When the cells were in logarithmic growth phase, they were treated with trypsin to separate them from the floor of the tissue culture dishes. A biodegradable material, Pluronic F-127, was prefabricated and mixed with these cells, and then the cell-Pluronic compounds were seeded evenly into a polyglycolic acid （PGA）. Then the constructs were replanted to the autologous animals to repair the full-thickness skin defects. Histology and immunohistochemistry of the neotissue were observed in 1, 2, 4, and 8 postoperative weeks. Results. The cell-Pluronic F-127-PGA compounds repaired autologous full-thickness skin defects 1 week after implantation. Histologically, the tissue engineered skin was similar to the normal skin with stratified epidermis overlying a moderately thick collageneous dermis. Three of the structural proteins in the epidermal basement membrane zone, type IV collagen, laminin, and type VII collagen were detected using immunohistochemicai methods. Conclusions ： By studying the histology and immunohistochemistry of the neotissue, the bioengineered skin graft holds great promise for improving healing of the skin defects.展开更多
Knee osteoarthritis is a chronic disease caused by the deterioration of the knee joint due to various factors such as aging,trauma,and obesity,and the nonrenewable nature of the injured cartilage makes the treatment o...Knee osteoarthritis is a chronic disease caused by the deterioration of the knee joint due to various factors such as aging,trauma,and obesity,and the nonrenewable nature of the injured cartilage makes the treatment of osteoarthritis challenging.Here,we present a three-dimensional(3D)printed porous multilayer scaffold based on cold-water fish skin gelatin for osteoarticular cartilage regeneration.To make the scaffold,cold-water fish skin gelatin was combined with sodium alginate to increase viscosity,printability,and mechanical strength,and the hybrid hydrogel was printed according to a pre-designed specific structure using 3D printing technology.Then,the printed scaffolds underwent a double-crosslinking process to enhance their mechanical strength even further.These scaffolds mimic the structure of the original cartilage network in a way that allows chondrocytes to adhere,proliferate,and communicate with each other,transport nutrients,and prevent further damage to the joint.More importantly,we found that cold-water fish gelatin scaffolds were nonimmunogenic,nontoxic,and biodegradable.We also implanted the scaffold into defective rat cartilage for 12 weeks and achieved satisfactory repair results in this animal model.Thus,cold-water fish skin gelatin scaffolds may have broad application potential in regenerative medicine.展开更多
Background:Biomaterials are vital products used in clinical sectors as alternatives to several biological macromolecules for tissue engineering techniques owing to their numerous beneficial properties,including wound ...Background:Biomaterials are vital products used in clinical sectors as alternatives to several biological macromolecules for tissue engineering techniques owing to their numerous beneficial properties,including wound healing.The healing pattern generally depends upon the type of wounds,and restoration of the skin on damaged areas is greatly dependent on the depth and severity of the injury.The rate of wound healing relies on the type of biomaterials being incorporated for the fabrication of skin substitutes and their stability in in vivo conditions.In this review,a systematic literature search was performed on several databases to identify the most frequently used biomaterials for the development of successful wound healing agents against skin damage,along with their mechanisms of action.Method:The relevant research articles of the last 5 years were identified,analysed and reviewed in this paper.The meta-analysis was carried out using PRISMA and the search was conducted in major scientific databases.The research of the most recent 5 years,from 2017-2021 was taken into consideration.The collected research papers were inspected thoroughly for further analysis.Recent advances in the utilization of natural and synthetic biomaterials(alone/in combination)to speed up the regeneration rate of injured cells in skin wounds were summarised.Finally,23 papers were critically reviewed and discussed.Results:In total,2022 scholarly articles were retrieved from databases utilizing the aforementioned input methods.After eliminating duplicates and articles published before 2017,∼520 articles remained that were relevant to the topic at hand(biomaterials for wound healing)and could be evaluated for quality.Following different procedures,23 publications were selected as best fitting for data extraction.Preferred Reporting Items for Systematic Reviews and Meta-Analyses for this review illustrates the selection criteria,such as exclusion and inclusion parameters.The 23 recent publications pointed to the use of both natural and synthetic polymers in wound healing applications.Information related to wound type and the mechanism of action has also been reviewed carefully.The selected publication showed that composites of natural and synthetic polymers were used extensively for both surgical and burn wounds.Extensive research revealed the effects of polymer-based biomaterials in wound healing and their recent advancement.Conclusions:The effects of biomaterials in wound healing are critically examined in this review.Different biomaterials have been tried to speed up the healing process,however,their success varies with the severity of the wound.However,some of the biomaterials raise questions when applied on a wide scale because of their scarcity,high transportation costs and processing challenges.Therefore,even if a biomaterial has good wound healing qualities,it may be technically unsuitable for use in actual medical scenarios.All of these restrictions have been examined closely in this review.展开更多
The use of polymer based composites in the treatment of skin tissue damages,has got huge attention in clinical demand,which enforced the scientists to improve the methods of biopolymer designing in order to obtain hig...The use of polymer based composites in the treatment of skin tissue damages,has got huge attention in clinical demand,which enforced the scientists to improve the methods of biopolymer designing in order to obtain highly efficient system for complete restoration of damaged tissue.In last few decades,chitosan-based biomaterials have major applications in skin tissue engineering due to its biocompatible,hemostatic,antimicrobial and biodegradable capabilities.This article overviewed the promising biological properties of chitosan and further discussed the various preparation methods involved in chitosan-based biomaterials.In addition,this review also gave a comprehensive discussion of different forms of chitosan-based biomaterials including membrane,sponge,nanofiber and hydrogel that were extensively employed in skin tissue engineering.This review will help to form a base for the advanced applications of chitosan-based biomaterials in treatment of skin tissue damages.展开更多
Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.A...Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although 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 challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In 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 model.Thus,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.展开更多
基金suppor ted by the National Key Research and Development Program of China(2022YFA1104800)the Beijing Nova Program(20220484100)+6 种基金the National Natural Science Foundation of China(81873939)the Open Research Fund of State Key Laboratory of Cardiovascular Disease,Fuwai Hospital(2022KF-04)the Clinical Medicine Plus X-Young Scholars Projec t,Pek ing Universit y(PKU2022LCXQ003)the Emerging Engineering InterdisciplinaryYoung Scholars Project,Peking University,the Fundamental Research Funds for the Central Universities(PKU2023XGK011)the Open Research Fund of State Key Laboratory of Digital Medical Engineering,Southeast University(2023K-01)the Open Research Fund of Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease,Beijing,China(DXWL2023-01)the Science and Technology Bureau Foundation Application Project of Changzhou(CJ20220118)。
文摘Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.
文摘In a general wound healing process, foreign bodies and tissue detritus have to be broken down and then a new tissue is produced. However, the new tissue formation sometimes fails to proceed under the impaired conditions such as burn injury and intractable skin ulcer. A major obstruction to wound healing is infection. Another obstruction to wound healing is deficiency of growth factors. The endogenous levels of growth factors are reduced in some chronic wounds. To improve these wound conditions, researchers have been trying to create several types of artificial skins. The tissue-engineered products include three prime constituents, i.e., cells, growth factors, and materials. In this review, the practical design of tissue-engineered products for skin regenerative medicine is introduced. The first design makes it possible to release silver sulfadiazine (AgSD) from a wound dressing. The second design makes it possible to release Epidermal Growth Factor (EGF) from a wound dressing or a skin care product composed of hyaluronic acid spongy sheet containing bioactive ingredients. The third design makes it possible to release several types of growth factors from allogeneic fibroblasts within cultured dermal substitute. This tissue-engineered product is prepared by seeding allogeneic fibroblasts into a collagen and hyaluronic acid spongy sheet. Although allogeneic cells are rejected gradually in immune system, they are able to release some types of growth factors, thereby regenerating a damaged tissue. The clinical study demonstrates that these tissue-engineered products are promising for the treatment of burn injury and intractable skin ulcer.
基金supported by the National Natural Science Foundation of ChinaNo.81130080
文摘Angiogenesis is a key process in regenerative medicine generally, as well as in the specific field of nerve regeneration. However, no convenient and objective method for evaluating the angiogenesis of tissue-engineered nerves has been reported. In this study, tissue-engineered nerves were constructed in vitro using Schwann cells differentiated from rat skin-derived precursors as supporting cells and chitosan nerve conduits combined with silk fibroin fibers as scaffolds to bridge 10-mm sciatic nerve defects in rats. Four weeks after surgery, three-dimensional blood vessel reconstructions were made through MICROFIL perfusion and micro-CT scanning, and parameter analysis of the tissue-engineered nerves was performed. New blood vessels grew into the tissue-engineered nerves from three main directions： the proximal end, the distal end, and the middle. The parameter analysis of the three-dimensional blood vessel images yielded several parameters, including the number, diameter, connection, and spatial distribution of blood vessels. The new blood vessels were mainly capillaries and microvessels, with diameters ranging from 9 to 301 μm. The blood vessels with diameters from 27 to 155 μm accounted for 82.84% of the new vessels. The microvessels in the tissue-engineered nerves implanted in vivo were relatively well-identified using the MICROFIL perfusion and micro-CT scanning method, which allows the evaluation and comparison of differences and changes of angiogenesis in tissue-engineered nerves implanted in vivo.
基金Supported by Postgraduate Research Grant Scheme of Universiti Sains Malaysia,No.1001/PPSP/8144012Techno Fund grant from the Ministry of Science,Technology and Innovation of Malaysia,No.304/PPSP/6150101
文摘Tissue engineering essentially refers to technology for growing new human tissue and is distinct from regenerative medicine. Currently, pieces of skin are already being fabricated for clinical use and many other tissue types may be fabricated in the future.Tissue engineering was first defined in 1987 by the United States National Science Foundation which critically discussed the future targets of bioengineering research and its consequences. The principles of tissue engineering are to initiate cell cultures in vitro, grow them on scaffolds in situ and transplant the composite into a recipient in vivo. From the beginning, scaffolds have been necessary in tissue engineering applications. Regardless, the latest technology has redirected established approaches by omitting scaffolds. Currently, scientists from diverse research institutes are engineering skin without scaffolds. Due to their advantageous properties, stem cells have robustly transformed the tissue engineering field as part of an engineered bilayered skin substitute that will later be discussed in detail. Additionally, utilizing biomaterials or skin replacement products in skin tissue engineering as strategy to successfully direct cell proliferation and differentiation as well as to optimize the safety of handling during grafting is beneficial. This approach has also led to the cells' application in developing the novel skin substitute that will be briefly explained in this review.
文摘Derma is progenitor cells sours, that are able to differentiate further in several mesodermal lineage and neural and endodermal lineage. Culture conditions, skin taking site and culture medium composition considerably contribute to it. Spheroid cultured mesenchymal dermal cells contribution to skin regeneration in granulating wound in rat model was estimated.
基金funded by the Instituto de Salud Carlos III through the project PI17/02083(co-funded by the European Regional Development Fund“A way to make Europe”)the RegionalGovernment of Andalusia(PIGE-0242-2019)+2 种基金the Canadian Institutes for Health Research(CIHR)(FDN-143213 and IC-132948)the Fondation des Pompiers du Québec pour les Grands Brûlés(FPQGB)the Quebec Network for Cell,Tissue and Gene Therapy-ThéCell(a thematic network supported by the Fonds de Recherche du Québec-Santé[FRQS]).
文摘Background:The aim of this in vitro study was to compare side-by-side two models of human bilayered tissue-engineered skin substitutes(hbTESSs)designed for the treatment of severely burned patients.These are the scaffold-free self-assembled skin substitute(SASS)and the human plasma-based skin substitute(HPSS).Methods:Fibroblasts and keratinocytes from three humans were extracted from skin biopsies(N=3)and cells from the same donor were used to produce both hbTESS models.For SASS manu-facture,keratinocytes were seeded over three self-assembled dermal sheets comprising fibroblasts and the extracellular matrix they produced(n=12),while for HPSS production,keratinocytes were cultured over hydrogels composed of fibroblasts embedded in either plasma as unique biomaterial(Fibrin),plasma combined with hyaluronic acid(Fibrin-HA)or plasma combined with collagen(Fibrin-Col)(n/biomaterial=9).The production time was 46-55 days for SASSs and 32-39 days for HPSSs.Substitutes were characterized by histology,mechanical testing,PrestoBlue™-assay,immunofluorescence(Ki67,Keratin(K)10,K15,K19,Loricrin,type IV collagen)and Western blot(type I and IV collagens).Results:The SASSs were more resistant to tensile forces(p-value<0.01)but less elastic(p-value<0.001)compared to HPSSs.A higher number of proliferative Ki67+cells were found in SASSs although their metabolic activity was lower.After epidermal differentiation,no significant difference was observed in the expression of K10,K15,K19 and Loricrin.Overall,the production of type I and type IV collagens and the adhesive strength of the dermal-epidermal junction was higher in SASSs.Conclusions:This study demonstrates,for the first time,that both hbTESS models present similar in vitro biological characteristics.However,mechanical properties differ and future in vivo experiments will aim to compare their wound healing potential.
基金This work was supported by the National Basic Research Program of China （973 Program, 2014CB542202）, the National HiTech Research and Development Program of China （863 Program, 2012AA020502）, the National Natural Science Foundation of China （81130080 and 31300879）, and the Key University Science Research Project of Jiangsu Province （16KJA310005）. It was also a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions （PAPD）.
文摘Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs(ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering.The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.
基金supported by National Institutes of Health Award R01DE028614,R56HL157190,R21AR082668,and R01AR078743,and 2236 CoCirculation2 of TUBITAK award 121C359.
文摘Craniomaxillofacial(CMF)reconstruction is a challenging clinical dilemma.It often necessitates skin replacement in the form of autologous graft or flap surgery,which differ from one another based on hypodermal/dermal content.Unfortunately,both approaches are plagued by scarring,poor cosmesis,inadequate restoration of native anatomy and hair,alopecia,donor site morbidity,and potential for failure.Therefore,new reconstructive approaches are warranted,and tissue engineered skin represents an exciting alternative.In this study,we demonstrated the reconstruction of CMF full-thickness skin defects using intraoperative bioprinting(IOB),which enabled the repair of defects via direct bioprinting of multiple layers of skin on immunodeficient rats in a surgical setting.Using a newly formulated patient-sourced allogenic bioink consisting of both human adipose-derived extracellular matrix(adECM)and stem cells(ADSCs),skin loss was reconstructed by precise deposition of the hypodermal and dermal components under three different sets of animal studies.adECM,even at a very low concentration such as 2%or less,has shown to be bioprintable via droplet-based bioprinting and exhibited de novo adipogenic capabilities both in vitro and in vivo.Our findings demonstrate that the combinatorial delivery of adECM and ADSCs facilitated the reconstruction of three full-thickness skin defects,accomplishing near-complete wound closure within two weeks.More importantly,both hypodermal adipogenesis and downgrowth of hair follicle-like structures were achieved in this two-week time frame.Our approach illustrates the translational potential of using human-derived materials and IOB technologies for full-thickness skin loss.
基金the National Natural Science Foundation of China(NSFC,82002298,51920105006,51973226)the China Postdoctoral Science Foundation(2020M670066)+1 种基金the National Key Research and Development Program of China(2016YFC1100704)the Youth Innovation Promotion Association CAS(2019031).
文摘Meniscus is a wedge-shaped fibrocartilaginous tissue,playing important roles in maintaining joint stability and function.Meniscus injuries are difficult to heal and frequently progress into structural breakdown,which then leads to osteoarthritis.Regeneration of heterogeneous tissue engineering meniscus(TEM)continues to be a scientific and translational challenge.The morphology,tissue architecture,mechanical strength,and functional applications of the cultivated TEMs have not been able to meet clinical needs,which may due to the negligent attention on the importance of microenvironment in vitro and in vivo.Herein,we combined the 3D(three-dimensional)-printed gradient porous scaffolds,spatiotemporal partition release of growth factors,and anti-inflammatory and anti-oxidant microenvironment regulation of Ac2-26 peptide to prepare a versatile meniscus composite scaffold with heterogeneous bionic structures,excellent biomechanical properties and anti-inflammatory and anti-oxidant effects.By observing the results of cell activity and differentiation,and biomechanics under anti-inflammatory and anti-oxidant microenvironments in vitro,we explored the effects of anti-inflammatory and anti-oxidant microenvironments on construction of regional and functional heterogeneous TEM via the growth process regulation,with a view to cultivating a high-quality of TEM from bench to bedside.
文摘Objective. To explore a feasible method to repair full-thickness skin defects utilizing tissue engineered techniques. Methods： The Changfeng hybrid swines were used and the skin specimens were cut from the posterior limb girdle region, from which the keratinocytes and fibroblasts were isolated and harvested by trypsin, EDTA, and type II collagenase. The cells were seeded in Petri dishes for primary culture. When the cells were in logarithmic growth phase, they were treated with trypsin to separate them from the floor of the tissue culture dishes. A biodegradable material, Pluronic F-127, was prefabricated and mixed with these cells, and then the cell-Pluronic compounds were seeded evenly into a polyglycolic acid （PGA）. Then the constructs were replanted to the autologous animals to repair the full-thickness skin defects. Histology and immunohistochemistry of the neotissue were observed in 1, 2, 4, and 8 postoperative weeks. Results. The cell-Pluronic F-127-PGA compounds repaired autologous full-thickness skin defects 1 week after implantation. Histologically, the tissue engineered skin was similar to the normal skin with stratified epidermis overlying a moderately thick collageneous dermis. Three of the structural proteins in the epidermal basement membrane zone, type IV collagen, laminin, and type VII collagen were detected using immunohistochemicai methods. Conclusions ： By studying the histology and immunohistochemistry of the neotissue, the bioengineered skin graft holds great promise for improving healing of the skin defects.
基金supported by the Key Program of NSFC(81730067)Major Project of NSFC(81991514)+3 种基金Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation,and Jiangsu Provincial Key Medical Talent Foundation.The Fundamental Research Funds for the Central Universities(14380493,14380494)the National Natural Science Foundation of China(82102511)the Natural Science Foundation of Jiangsu(BK20210021)Research Project of Jiangsu Province Health Committee(M2021031).
文摘Knee osteoarthritis is a chronic disease caused by the deterioration of the knee joint due to various factors such as aging,trauma,and obesity,and the nonrenewable nature of the injured cartilage makes the treatment of osteoarthritis challenging.Here,we present a three-dimensional(3D)printed porous multilayer scaffold based on cold-water fish skin gelatin for osteoarticular cartilage regeneration.To make the scaffold,cold-water fish skin gelatin was combined with sodium alginate to increase viscosity,printability,and mechanical strength,and the hybrid hydrogel was printed according to a pre-designed specific structure using 3D printing technology.Then,the printed scaffolds underwent a double-crosslinking process to enhance their mechanical strength even further.These scaffolds mimic the structure of the original cartilage network in a way that allows chondrocytes to adhere,proliferate,and communicate with each other,transport nutrients,and prevent further damage to the joint.More importantly,we found that cold-water fish gelatin scaffolds were nonimmunogenic,nontoxic,and biodegradable.We also implanted the scaffold into defective rat cartilage for 12 weeks and achieved satisfactory repair results in this animal model.Thus,cold-water fish skin gelatin scaffolds may have broad application potential in regenerative medicine.
文摘Background:Biomaterials are vital products used in clinical sectors as alternatives to several biological macromolecules for tissue engineering techniques owing to their numerous beneficial properties,including wound healing.The healing pattern generally depends upon the type of wounds,and restoration of the skin on damaged areas is greatly dependent on the depth and severity of the injury.The rate of wound healing relies on the type of biomaterials being incorporated for the fabrication of skin substitutes and their stability in in vivo conditions.In this review,a systematic literature search was performed on several databases to identify the most frequently used biomaterials for the development of successful wound healing agents against skin damage,along with their mechanisms of action.Method:The relevant research articles of the last 5 years were identified,analysed and reviewed in this paper.The meta-analysis was carried out using PRISMA and the search was conducted in major scientific databases.The research of the most recent 5 years,from 2017-2021 was taken into consideration.The collected research papers were inspected thoroughly for further analysis.Recent advances in the utilization of natural and synthetic biomaterials(alone/in combination)to speed up the regeneration rate of injured cells in skin wounds were summarised.Finally,23 papers were critically reviewed and discussed.Results:In total,2022 scholarly articles were retrieved from databases utilizing the aforementioned input methods.After eliminating duplicates and articles published before 2017,∼520 articles remained that were relevant to the topic at hand(biomaterials for wound healing)and could be evaluated for quality.Following different procedures,23 publications were selected as best fitting for data extraction.Preferred Reporting Items for Systematic Reviews and Meta-Analyses for this review illustrates the selection criteria,such as exclusion and inclusion parameters.The 23 recent publications pointed to the use of both natural and synthetic polymers in wound healing applications.Information related to wound type and the mechanism of action has also been reviewed carefully.The selected publication showed that composites of natural and synthetic polymers were used extensively for both surgical and burn wounds.Extensive research revealed the effects of polymer-based biomaterials in wound healing and their recent advancement.Conclusions:The effects of biomaterials in wound healing are critically examined in this review.Different biomaterials have been tried to speed up the healing process,however,their success varies with the severity of the wound.However,some of the biomaterials raise questions when applied on a wide scale because of their scarcity,high transportation costs and processing challenges.Therefore,even if a biomaterial has good wound healing qualities,it may be technically unsuitable for use in actual medical scenarios.All of these restrictions have been examined closely in this review.
文摘The use of polymer based composites in the treatment of skin tissue damages,has got huge attention in clinical demand,which enforced the scientists to improve the methods of biopolymer designing in order to obtain highly efficient system for complete restoration of damaged tissue.In last few decades,chitosan-based biomaterials have major applications in skin tissue engineering due to its biocompatible,hemostatic,antimicrobial and biodegradable capabilities.This article overviewed the promising biological properties of chitosan and further discussed the various preparation methods involved in chitosan-based biomaterials.In addition,this review also gave a comprehensive discussion of different forms of chitosan-based biomaterials including membrane,sponge,nanofiber and hydrogel that were extensively employed in skin tissue engineering.This review will help to form a base for the advanced applications of chitosan-based biomaterials in treatment of skin tissue damages.
基金The reported study was supported in part by research grants from the 2019 Chongqing Support Program for Entrepreneurship and Innovation(No.cx2019113)(JF)the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(KJQN201900410)(JF)+9 种基金the 2019 Youth Innovative Talent Training Program of Chongqing Education Commission(No.CY200409)(JF)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)(JF)and the National Key Research and Development Program of China(2016YFC1000803)RRR,TCH and GAA were partially funded by the National Institutes of Health(DE030480)WW was supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430TCH was also supported by the Mabel Green Myers Research Endowment Fund,The University of Chicago Orthopaedics Alumni Fund,and The University of Chicago SHOCK Fund.Funding sources were not involved in the study designin the collection,analysis and/or interpretation of datain the writing of the reportor in the decision to submit the paper for publication.
文摘Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although 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 challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In 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 model.Thus,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.
