The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In orde...The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In order to improve the safety, durability, elasticity, biocompatibility, and clinical efficacy of tissue-engineered skin, several powerful seed cells have already found their application in wound repair, and a variety of bioactive scaffolds have been discovered to influence cell fate in epidermogenesis. These exuberant interests provide insights into advanced construction strategies for complex skin mimics. Based on these exciting developments, a complete full-thickness tissue-engineered skin is likely to be generated.展开更多
Traumatic peripheral nerve injury is a worldwide clinical issue with high morbidity.The severity of peripheral nerve injury can be classified as neurapraxia,axonotmesis or neurotmesis,according to Seddon’s classifica...Traumatic peripheral nerve injury is a worldwide clinical issue with high morbidity.The severity of peripheral nerve injury can be classified as neurapraxia,axonotmesis or neurotmesis,according to Seddon’s classification,or five different degrees according to Sunderland’s classification.Patients with neurotmesis suffer from a complete transection of peripheral nerve stumps and are often in need of surgical repair of nerve defects.The applications of autologous nerve grafts as the golden standard for peripheral nerve transplantation meet some difficulties,including donor nerve sacrifice and nerve mismatch.Attempts have been made to construct tissue-engineered nerve grafts as supplements or even substitutes for autologous nerve grafts to bridge peripheral nerve defects.The incorporation of stem cells as seed cells into the biomaterial-based scaffolds increases the effectiveness of tissue-engineered nerve grafts and largely boosts the regenerative process.Numerous stem cells,including embryonic stem cells,neural stem cells,bone marrow mesenchymal stem cells,adipose stem cells,skin-derived precursor stem cells and induced pluripotent stem cells,have been used in neural tissue engineering.In the current review,recent trials of stem cell-based tissue-engineered nerve grafts have been summarized;potential concerns and perspectives of stem cell therapeutics have also been contemplated.展开更多
Background Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilica...Background Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilical cord blood-derived endothelial progenitor cells （EPCs） and decellularized valve scaffolds. Methods Decellularized valve scaffolds were prepared from fresh porcine heart valves. EPCs were isolated from fresh human umbilical cord blood by density gradient centrifugation, cultured for 3 weeks in EGM-2-MV medium, by which time the resultant cell population became endothelial in nature, as assessed by immunofluorescent staining. EPC-derived endothelial cells were seeded onto the decellularized scaffold at 3 × 10^6 cells/cm^2 and cultured under static conditions for 7 days. Proliferation of the seeded cells on the scaffolds was detected using the MTT assay. Tissue-engineered heart valves were analyzed by HE staining, immunofluorescent staining and scanning electron microscopy. The anti-thrombogenic function of the endothelium on the engineered heart valves was evaluated by platelet adhesion experiments and reverse transcription-polymerase chain reaction （RT-PCR） analysis for the expression of endothelial nitric oxide synthase （eNOS） and tissue-type plasminogen activator （t-PA）.Results EPC-derived endothelial cells showed a histolytic cobblestone morphology, expressed specific markers of the endothelial cell lineage including von Willebrand factor （vWF） and CD31, bound a human endothelial cell-specific lectin, Ulex Europaeus agglutinin-1 （UEA-1）, and took up Dil-labeled low density lipoprotein （Dil-Ac-LDL）. After seeding on the decellularized scaffold, the cells showed excellent metabolic activity and proliferation. The cells formed confluent endothelial monolayers atop the decellularized matrix, as assessed by HE staining and immunostaining for vWF and CD31. Scanning electron microscopy demonstrated the occurrence of tight junctions between cells forming the confluent monolay展开更多
Skeletal muscle-derived cells have strong secretory function,while skeletal muscle-derived stem cells,which are included in muscle-derived cells,can differentiate into Schwann cell-like cells and other cell types.Howe...Skeletal muscle-derived cells have strong secretory function,while skeletal muscle-derived stem cells,which are included in muscle-derived cells,can differentiate into Schwann cell-like cells and other cell types.However,the effect of muscle-derived cells on peripheral nerve defects has not been reported.In this study,5-mm-long nerve defects were created in the right sciatic nerves of mice to construct a peripheral nerve defect model.Adult female C57BL/6 mice were randomly divided into four groups.For the muscle-derived cell group,muscle-derived cells were injected into the catheter after the cut nerve ends were bridged with a polyurethane catheter.For external oblique muscle-fabricated nerve conduit and polyurethane groups,an external oblique muscle-fabricated nerve conduit or polyurethane catheter was used to bridge the cut nerve ends,respectively.For the sham group,the sciatic nerves on the right side were separated but not excised.At 8 and 12 weeks post-surgery,distributions of axons and myelin sheaths were observed,and the nerve diameter was calculated using immunofluorescence staining.The number,diameter,and thickness of myelinated nerve fibers were detected by toluidine blue staining and transmission electron microscopy.Muscle fiber area ratios were calculated by Masson’s trichrome staining of gastrocnemius muscle sections.Sciatic functional index was recorded using walking footprint analysis at 4,8,and 12 weeks after operation.The results showed that,at 8 and 12 weeks after surgery,myelin sheaths and axons of regenerating nerves were evenly distributed in the muscle-derived cell group.The number,diameter,and myelin sheath thickness of myelinated nerve fibers,as well as gastrocnemius muscle wet weight and muscle area ratio,were significantly higher in the muscle-derived cell group compared with the polyurethane group.At 4,8,and 12 weeks post-surgery,sciatic functional index was notably increased in the muscle-derived cell group compared with the polyurethane group.These criteria of the muscle-derived cel展开更多
The keratoprosthesis(KPro;artificial cornea)is a special refractive device to replace human cornea by using heterogeneous forming materials for the implantation into the damaged eyes in order to obtain a certain visio...The keratoprosthesis(KPro;artificial cornea)is a special refractive device to replace human cornea by using heterogeneous forming materials for the implantation into the damaged eyes in order to obtain a certain vision.The main problems of artificial cornea are the biocompatibility and stability of the tissue particularly in penetrating keratoplasty.The current studies of tissue-engineered scaffold materials through comprising composites of natural and synthetic biopolymers together have developed a new way to artificial cornea.Although a wide agreement that the long-term stability of these devices would be greatly improved by the presence of cornea cells,modification of keratoprosthesis to support cornea cells remains elusive.Most of the studies on corneal substrate materials and surface modification of composites have tried to improve the growth and biocompatibility of cornea cells which can not only reduce the stimulus of heterogeneous materials,but also more importantly continuous and stable cornea cells can prevent the destruction of collagenase.The necrosis of stroma and spontaneous extrusion of the device,allow for maintenance of a precorneal tear layer,and play the role of ensuring a good optical surface and resisting bacterial infection.As a result,improvement in corneal cells has been the main aim of several recent investigations;some effort has focused on biomaterial for its well biological properties such as promoting the growth of cornea cells.The purpose of this review is to summary the growth status of the corneal cells after the implantation of several artificial corneas.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
The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies to diseases such as osteoarthritis.Tissue engineering has been proposed as a promising strategy to meet the ...The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies to diseases such as osteoarthritis.Tissue engineering has been proposed as a promising strategy to meet the demand of simultaneous regeneration of both cartilage and subchondral bone by constructing integrated gradient tissue-engineered osteochondral scaffold(IGTEOS).This review brought forward the main challenges of establishing a satisfactory IGTEOS from the perspectives of the complexity of physiology and microenvironment of osteochondral tissue,and the limitations of obtaining the desired and required scaffold.Then,we comprehensively discussed and summarized the current tissue-engineered efforts to resolve the above challenges,including architecture strategies,fabrication techniques and in vitro/in vivo evaluation methods of the IGTEOS.Especially,we highlighted the advantages and limitations of various fabrication techniques of IGTEOS,and common cases of IGTEOS application.Finally,based on the above challenges and current research progress,we analyzed in details the future perspectives of tissue-engineered osteochondral construct,so as to achieve the perfect reconstruction of the cartilaginous and osseous layers of osteochondral tissue simultaneously.This comprehensive and instructive review could provide deep insights into our current understanding of IGTEOS.展开更多
The rapid endothelialization of tissue-engineered blood vessels(TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for th...The rapid endothelialization of tissue-engineered blood vessels(TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for the treatment of cardiovascular diseases.β-cyclodextrin sulfate is a type of hollow molecule that has good biocompatibility and anticoagulation properties and exhibits a sustained release of icariin. We studied whether icariin-loaded β-cyclodextrin sulfate can promote the endothelialization of TEBVs. The experimental results showed that icariin could significantly promote the proliferation and migration of endothelial progenitor cells; at the same time, icariin could promote the migration of rat vascular endothelial cells(RAVECs). Subsequently,we used an electrostatic force to modify the surface of the TEBVs with icariin-loaded β-cyclodextrin sulfate, and these vessels were implanted into the rat common carotid artery. After 3 months, micro-CT results showed that the TEBVs modified using icariin-loaded β-cyclodextrin sulfate had a greater patency rate. Scanning electron microscopy(SEM) and CD31 immunofluorescence results showed a better degree of endothelialization. Taken together, icariin-loaded β-cyclodextrin sulfate can achieve anticoagulation and rapid endothelialization of TEBVs to ensure their long-term patency.展开更多
To create a scaffold that is suitable for the construction of tissue-engineered skin, a novel asymmetric porous scaffold with different pore sizes on either side was prepared by combining a collagen-chitosan porous me...To create a scaffold that is suitable for the construction of tissue-engineered skin, a novel asymmetric porous scaffold with different pore sizes on either side was prepared by combining a collagen-chitosan porous membrane with fibrin glue. Tissue-engineered skin was fabricated using this asymmetric scaffold, fibroblasts, and a human keratinocyte line (HaCaT). Epidermal cells could be seen growing easily and achieved confluence on the fibrin glue on the upper surface of the scaffold. Scanning electron microscopy showed typical shuttle-like fibroblasts adhering to the wall of the scaffold and fluorescence microscopy showed them growing in the dermal layer of the scaffold. The constructed composite skin substitute had a histological structure similar to that of normal skin tissue after three weeks of culture. The results of our study suggest that the asymmetric scaffold is a promising biologically functional material for skin tissue engineering, with prospects for clinical applications.展开更多
AIM: To evaluate the biological functions of tissue-engineered human corneal epithelium (TE-HCEP) by corneal transplantation in limbal stem cell deficiency (LSCD) rabbit models. METHODS: TE-HCEPs were reconstructed wi...AIM: To evaluate the biological functions of tissue-engineered human corneal epithelium (TE-HCEP) by corneal transplantation in limbal stem cell deficiency (LSCD) rabbit models. METHODS: TE-HCEPs were reconstructed with DiI-labeled untransfected HCEP cells and denuded amniotic membrane (dAM) in air-liquid interface culture, and their morphology and structure were characterized by hematoxylin-eosin (HE) staining of paraffin-sections, immunohistochemistry and electron microscopy. LSCD models were established by mechanical and alcohol treatment of the left eyes of New Zealand white rabbits, and their eyes were transplanted with TE-HCEPs with dAM surface outside by lamellar keratoplasty (LKP). Corneal transparency, neovascularization, thickness, and epithelial integrality of both traumatic and post transplantation eyes were checked once a week by slit-lamp corneal microscopy, a corneal pachymeter, and periodic acid-Schiff (PAS) staining. At day 120 post surgery, the rabbits in each group were sacrificed and their corneas were examined by DiI label observation, HE staining, immunohistochemistry and electron microscopy. RESULTS: After cultured for 5 days on dAM, HCEP cells, maintaining keratin 3 expression, reconstructed a 6-7 layer TE-HCEP with normal morphology and structure. The traumatic rabbit corneas, entirely opaque, conjunctivalized and with invaded blood vessels, were used as LSCD models for TE-HCEP transplantation. After transplantation, obvious edema was not found in TE-HCEP-transplanted corneas which became more and more transparent, the invaded blood vessels reduced gradually throughout the monitoring period. The corneas decreased to normal thickness on day 25, while those of dAM eyes were over 575 mu m in thickness during the monitoring period. A 45 layer of epithelium consisting of TE-HCEP originated cells attached tightly to the anterior surface of stroma was reconstructed 120 days after TE-HCEP transplantation, which was similar to the normal control eye in morphology and structure. In contrast, intens展开更多
Background： A major shortcoming in tissue engineered blood vessels （TEBVs） is the lack of healthy and easily attainable smooth muscle cells （SMCs）. Smooth muscle progenitor cells （SPCs）, especially from periphe...Background： A major shortcoming in tissue engineered blood vessels （TEBVs） is the lack of healthy and easily attainable smooth muscle cells （SMCs）. Smooth muscle progenitor cells （SPCs）, especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. Methods： SPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV （EGM-2-MV） medium containing platelet-derived growth factoroBB （PDGF BB）. Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell （SOC） phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction （RT-PCR）. The cells were seeded onto the silk fibroin-modified poly（3-hydroxybutyrate-co-3-hydroxyhexanoate） （SF-PHBHHx） scaflblds by 6× 10^4 cells/cm^2 and cultured under the static condition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-（4,5-dimethylthiazol-2-yl）-diphenyltetrazolium bromide （MTT） assay, scanning electron microscope （SEM）, and 4,6-diamidino-2-phenylindole （DAPI） staining. Results： SOCs displayed specific ＂hill and valley＂ morphology, expressed the specific markers of the SMC lineage： smooth muscle （SM） a-actin, calponin and smooth muscle myosin heavy chain （SM MHC） at protein and messenger ribonucleic acid （mRNA） levels. RT-PCR results demonstrate that SOCs also expressed smooth muscle protein 22a （SM22a, a contractile protein, and extracellular matrix components elastin and matrix Gla protein （MGP）, as well as vascular endothelial growth factor （VEGF）. After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation. Conclusion： SPCs isolated from peripheral blood can be differentiated the SMCs in vitro and have an impressive growth potential in the 展开更多
AIM: To demonstrate the morphology and structure of in vitro reconstructed tissue-engineered human corneal epithelium (TE-HCEP) with seeder cells from an untransfected HCEP cell line. METHODS: The TE-HCEPs were recons...AIM: To demonstrate the morphology and structure of in vitro reconstructed tissue-engineered human corneal epithelium (TE-HCEP) with seeder cells from an untransfected HCEP cell line. METHODS: The TE-HCEPs were reconstructed in vitro with seeder cells from an untransfected HCEP cell line, and scaffold carriers of denuded amniotic membrane (dAM) in air-liquid interface culture for 3, 5, 7 and 9 days, respectively. The specimens were examined with hematoxylin-eosin (HE) staining of paraffin-section, immunocytochemical staining, scanning and transmission electron microscopy. RESULTS: During in vitro reconstruction of TE-HCEP, HCEP cells formed a 3-4, 6-7 and 8-10 layers of an HCEP-like structure on dAMs in air-liquid interface culture for 3, 5 and 7 days, respectively. But the cells deceased to 5-6 layers and the structure of straified epithelium became loose at day 9. And the cells maintained positive expression of marker proteins (keratin 3 and keratin 12), cell-junction proteins (zonula occludens-1, E-cadherin, connexin 43 and integrin beta 1) and membrane transport protein of Na+-K+ ATPase. The HCEP cells in TE-HCEP were rich in microvilli on apical surface and established numerous cell-cell and cell-dAM junctions at day 5. CONCLUSION: The morphology and structure of the reconstructed TE-HCEP were similar to those of HCEP in vivo. The HCEP cells in the reconstructed TE-HCEP maintained the properties of HCEP cells, including abilities of forming intercellular and cell-extracellular matrix junctions and abilities of performing membrane transportation. The untransfected HCEP cells and dAMs could promisingly be used in reconstruction HCEP equivalent for clinical corneal epithelium transplantation.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are common in patients with diabetes,especially those undergoing hemodialysis.In severe cases,these ulcers can cause damage to the lower extremities and lead to amputation.Traditio...BACKGROUND Diabetic foot ulcers(DFUs)are common in patients with diabetes,especially those undergoing hemodialysis.In severe cases,these ulcers can cause damage to the lower extremities and lead to amputation.Traditional treatments such as flap transposition and transfemoral amputation are not always applicable in all cases.Therefore,there is a need for alternative treatment methods.CASE SUMMARY This report describes a 62-year-old female patient who was admitted to the hospital with plantar and heel ulcers on her left foot.The patient had a history of renal failure and was undergoing regular hemodialysis.Digital subtraction angiography showed extensive stenosis and occlusion in the left superficial femoral artery,left peroneal artery and left posterior tibial artery.Following evaluation by a multidisciplinary team,the patient was diagnosed with type 2 DFUs(TEXAS 4D).Traditional treatments were deemed unsuitable,and the patient was treated with endovascular surgery in the affected area,in addition to supportive medical treatment,local debridement,and sequential repair using split-thickness skin and tissue-engineered skin grafts combined with negative pressure treatment.After four months,the wound had completely healed,and the patient was able to walk with a walking aid.CONCLUSION This study demonstrates a new treatment method for DFUs was successful,using angioplasty,skin grafts,and negative pressure.展开更多
BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological r...BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological rejections. Cells that do not induce immunological rejections and that are relatively easy to acquire are urgently needed for transplantation. OBJECTIVE： To bridge sciatic nerve defects using tissue engineered nerves constructed with neural tissue-committed stem cells （NTCSCs） derived from bone marrow; to observe morphology and function of rat nerves following bridging; to determine the effect of autologous nerve transplantation, which serves as the gold standard for evaluating efficacy of tissue-engineered nerves. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed in the Anatomical Laboratory and Biomedical Institute of the Second Military Medical University of Chinese PLA between September 2004 and April 2006. MATERIALS： Five Sprague Dawley rats, aged 1 month and weighing 100-150 g, were used for cell culture. Sixty Sprague Dawley rats aged 3 months and weighing 220-250 g, were used to establish neurological defect models. Nestin, neuron-specific enolase （NSE）, glial fibrillary acidic protein （GFAP）, and S-100 antibodies were provided by Santa Cruz Biotechnology, Inc., USA. Acellular nerve grafts were derived from dogs. METHODS： All rats, each with 1-cm gap created in the right sciatic nerve, were randomly assigned to three groups. Each group comprised 20 rats. Autograft nerve transplantation group： the severed 1-cm length nerve segment was reverted, but with the two ends exchanged; the proximal segment was sutured to the distal sciatic nerve stump and the distal segment to the proximal stump. Blank nerve scaffold transplantation group： a 1-cm length acellular nerve graft was used to bridge the sciatic nerve gap. NTCSC engineered nerve transplantation group： a 1-cm length acellular nerve graft, in which NTCSCs were inoculated, was used t展开更多
Urethral stricture disease is increasingly common occurring in about 1%of males over the age of 55.The stricture tissue is rich in myofibroblasts and multi-nucleated giant cells which are thought to be related to stri...Urethral stricture disease is increasingly common occurring in about 1%of males over the age of 55.The stricture tissue is rich in myofibroblasts and multi-nucleated giant cells which are thought to be related to stricture formation and collagen synthesis.An increase in collagen is associated with the loss of the normal vasculature of the normal urethra.The actual incidence differs based on worldwide populations,geography,and income.The stricture aetiology,location,length and patient’s age and comorbidity are important in deciding the course of treatment.In this review we aim to summarise the existing knowledge of the aetiology of urethral strictures,review current treatment regimens,and present the challenges of using tissue-engineered buccal mucosa(TEBM)to repair scarring of the urethra.In asking this question we are also mindful that recurrent fibrosis occurs in other tissuesdhow can we learn from these other pathologies?展开更多
To evaluate the therapeutic efficiency of tissue-engineered human corneal endothelia (TE-HCEs) on rabbit primary corneal endotheliopathy (PCEP),TE-HCEs reconstructed with monoclonal human corneal endothelial cells (mc...To evaluate the therapeutic efficiency of tissue-engineered human corneal endothelia (TE-HCEs) on rabbit primary corneal endotheliopathy (PCEP),TE-HCEs reconstructed with monoclonal human corneal endothelial cells (mcHCECs) and modified denuded amniotic membranes (mdAMs) were transplanted into PCEP models of New Zealand white rabbits using penetrating keratoplasty.The TE-HCEs were examined using diverse techniques including slit-lamp biomicroscopy observation and pachymeter and tonometer measurements in vivo,and fluorescent microscopy,alizarin red staining,paraffin sectioning,scanning and transmission electron microscopy observations in vitro.The corneas of transplanted eyes maintained transparency for as long as 200 d without obvious edema or immune rejection.The corneal thickness of transplanted eyes decreased gradually after transplanting,reaching almost the thickness of normal eyes after 156 d,while the TE-HCE non-transplanted eyes were turbid and showed obvious corneal edema.The polygonal corneal endothelial cells in the transplanted area originated from the TE-HCE transplant.An intact monolayer corneal endothelium had been reconstructed with the morphology,cell density and structure similar to those of normal rabbit corneal endothelium.In conclusion,the transplanted TE-HCE can reconstruct the integrality of corneal endothelium and restore corneal transparency and thickness in PCEP rabbits.The TE-HCE functions normally as an endothelial barrier and pump and promises to be an equivalent of HCE for clinical therapy of human PCEP.展开更多
Treatment of acute and chronic wounds is one of the primary challenges faced by doctors.Bioderived materials have significant potential clinical value in tissue injury treatment and defect reconstruction.Various strat...Treatment of acute and chronic wounds is one of the primary challenges faced by doctors.Bioderived materials have significant potential clinical value in tissue injury treatment and defect reconstruction.Various strategies,including drug loading,addition of metallic element(s),crosslinking and combining two or more distinct types of materials with complementary features,have been used to synthesize more suitable materials for wound healing.In this review,we describe the recent developments made in the processing of bioderived materials employed for cutaneous wound healing,including newly developed materials such as keratin and soy protein.The focus was on the key properties of the bioderived materials that have shown great promise in improving wound healing,restoration and reconstruction.With their good biocompatibility,nontoxic catabolites,microinflammation characteristics,as well as their ability to induce tissue regeneration and reparation,the bioderived materials have great potential for skin tissue repair.展开更多
Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidire...Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidirectional differentiation potential. A large amount of data confirmed that CS-MSCs can be induced to differentiate into functional keratocytes in vitro, which is the motive force for maintaining corneal transparency and producing a normal corneal stroma. CS-MSCs are also an important component of the limbal microenvironment. Furthermore, they are of great significance in the reconstruction of ocular surface tissue and tissue engineering for active biocornea construction. In this paper, the localization and biological characteristics of CS-MSCs, the use of CS-MSCs to reconstruct a tissue-engineered active biocornea, and the repair of the limbal and matrix microenvironment by CS-MSCs are reviewed, and their application prospects are discussed.展开更多
Tissue-engineered vascular grafts(TEVGs)have enormous potential for vascular replacement therapy.However,thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs(...Tissue-engineered vascular grafts(TEVGs)have enormous potential for vascular replacement therapy.However,thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs(<6 mm)after transplantation.Endothelialization of TEVGs is a key point to prevent thrombosis.Here,we discuss different types of endothelialization and different seed cells of tissue-engineered vascular grafts.Meanwhile,endothelial heterogeneity is also discussed.Based on it,we provide a new perspective for selecting suitable types of endothelialization and suitable seed cells to improve the long-term patency rate of tissue-engineered vascular grafts with different diameters and lengths.展开更多
基金a grant from National High Technology Research and Development Program of China (863 Program) (2012AA020507)
文摘The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In order to improve the safety, durability, elasticity, biocompatibility, and clinical efficacy of tissue-engineered skin, several powerful seed cells have already found their application in wound repair, and a variety of bioactive scaffolds have been discovered to influence cell fate in epidermogenesis. These exuberant interests provide insights into advanced construction strategies for complex skin mimics. Based on these exciting developments, a complete full-thickness tissue-engineered skin is likely to be generated.
基金supported by the National Major Project of Research and Development[grant numbers 2017YFA0104700,2016YFC1101603]the National Natural Science Foundation of China[grant numbers 31730031,31700926]Jiangsu Provincial Key Medical Center and the Priority Academic Program Development of Jiangsu Higher Education Institutions of China[PAPD].
文摘Traumatic peripheral nerve injury is a worldwide clinical issue with high morbidity.The severity of peripheral nerve injury can be classified as neurapraxia,axonotmesis or neurotmesis,according to Seddon’s classification,or five different degrees according to Sunderland’s classification.Patients with neurotmesis suffer from a complete transection of peripheral nerve stumps and are often in need of surgical repair of nerve defects.The applications of autologous nerve grafts as the golden standard for peripheral nerve transplantation meet some difficulties,including donor nerve sacrifice and nerve mismatch.Attempts have been made to construct tissue-engineered nerve grafts as supplements or even substitutes for autologous nerve grafts to bridge peripheral nerve defects.The incorporation of stem cells as seed cells into the biomaterial-based scaffolds increases the effectiveness of tissue-engineered nerve grafts and largely boosts the regenerative process.Numerous stem cells,including embryonic stem cells,neural stem cells,bone marrow mesenchymal stem cells,adipose stem cells,skin-derived precursor stem cells and induced pluripotent stem cells,have been used in neural tissue engineering.In the current review,recent trials of stem cell-based tissue-engineered nerve grafts have been summarized;potential concerns and perspectives of stem cell therapeutics have also been contemplated.
基金the grants from Shanghai Science Committee Fund for Key Research Project(No.04JC14012)Fudan University Med-X Fund Abstract
文摘Background Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilical cord blood-derived endothelial progenitor cells （EPCs） and decellularized valve scaffolds. Methods Decellularized valve scaffolds were prepared from fresh porcine heart valves. EPCs were isolated from fresh human umbilical cord blood by density gradient centrifugation, cultured for 3 weeks in EGM-2-MV medium, by which time the resultant cell population became endothelial in nature, as assessed by immunofluorescent staining. EPC-derived endothelial cells were seeded onto the decellularized scaffold at 3 × 10^6 cells/cm^2 and cultured under static conditions for 7 days. Proliferation of the seeded cells on the scaffolds was detected using the MTT assay. Tissue-engineered heart valves were analyzed by HE staining, immunofluorescent staining and scanning electron microscopy. The anti-thrombogenic function of the endothelium on the engineered heart valves was evaluated by platelet adhesion experiments and reverse transcription-polymerase chain reaction （RT-PCR） analysis for the expression of endothelial nitric oxide synthase （eNOS） and tissue-type plasminogen activator （t-PA）.Results EPC-derived endothelial cells showed a histolytic cobblestone morphology, expressed specific markers of the endothelial cell lineage including von Willebrand factor （vWF） and CD31, bound a human endothelial cell-specific lectin, Ulex Europaeus agglutinin-1 （UEA-1）, and took up Dil-labeled low density lipoprotein （Dil-Ac-LDL）. After seeding on the decellularized scaffold, the cells showed excellent metabolic activity and proliferation. The cells formed confluent endothelial monolayers atop the decellularized matrix, as assessed by HE staining and immunostaining for vWF and CD31. Scanning electron microscopy demonstrated the occurrence of tight junctions between cells forming the confluent monolay
基金financially supported by the National Natural Science Foundation of China,No.81671908(to ZLQ)and No.81571921(to XNY)the Fundamental Research Fund for the Central Universities of China,No.2016ZX310197(to ZLQ)+1 种基金the Union Youth Science&Research Foundation of China,No.3332015155(to XNY)the Science Fund of Plastic Surgery Hospital,Chinese Academy of Medical Sciences,and Peking Union Medical College of China,No.Q2015013(to XNY)
文摘Skeletal muscle-derived cells have strong secretory function,while skeletal muscle-derived stem cells,which are included in muscle-derived cells,can differentiate into Schwann cell-like cells and other cell types.However,the effect of muscle-derived cells on peripheral nerve defects has not been reported.In this study,5-mm-long nerve defects were created in the right sciatic nerves of mice to construct a peripheral nerve defect model.Adult female C57BL/6 mice were randomly divided into four groups.For the muscle-derived cell group,muscle-derived cells were injected into the catheter after the cut nerve ends were bridged with a polyurethane catheter.For external oblique muscle-fabricated nerve conduit and polyurethane groups,an external oblique muscle-fabricated nerve conduit or polyurethane catheter was used to bridge the cut nerve ends,respectively.For the sham group,the sciatic nerves on the right side were separated but not excised.At 8 and 12 weeks post-surgery,distributions of axons and myelin sheaths were observed,and the nerve diameter was calculated using immunofluorescence staining.The number,diameter,and thickness of myelinated nerve fibers were detected by toluidine blue staining and transmission electron microscopy.Muscle fiber area ratios were calculated by Masson’s trichrome staining of gastrocnemius muscle sections.Sciatic functional index was recorded using walking footprint analysis at 4,8,and 12 weeks after operation.The results showed that,at 8 and 12 weeks after surgery,myelin sheaths and axons of regenerating nerves were evenly distributed in the muscle-derived cell group.The number,diameter,and myelin sheath thickness of myelinated nerve fibers,as well as gastrocnemius muscle wet weight and muscle area ratio,were significantly higher in the muscle-derived cell group compared with the polyurethane group.At 4,8,and 12 weeks post-surgery,sciatic functional index was notably increased in the muscle-derived cell group compared with the polyurethane group.These criteria of the muscle-derived cel
基金National Natural Science Foundation of China(No.50973082)
文摘The keratoprosthesis(KPro;artificial cornea)is a special refractive device to replace human cornea by using heterogeneous forming materials for the implantation into the damaged eyes in order to obtain a certain vision.The main problems of artificial cornea are the biocompatibility and stability of the tissue particularly in penetrating keratoplasty.The current studies of tissue-engineered scaffold materials through comprising composites of natural and synthetic biopolymers together have developed a new way to artificial cornea.Although a wide agreement that the long-term stability of these devices would be greatly improved by the presence of cornea cells,modification of keratoprosthesis to support cornea cells remains elusive.Most of the studies on corneal substrate materials and surface modification of composites have tried to improve the growth and biocompatibility of cornea cells which can not only reduce the stimulus of heterogeneous materials,but also more importantly continuous and stable cornea cells can prevent the destruction of collagenase.The necrosis of stroma and spontaneous extrusion of the device,allow for maintenance of a precorneal tear layer,and play the role of ensuring a good optical surface and resisting bacterial infection.As a result,improvement in corneal cells has been the main aim of several recent investigations;some effort has focused on biomaterial for its well biological properties such as promoting the growth of cornea cells.The purpose of this review is to summary the growth status of the corneal cells after the implantation of several artificial corneas.
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support from the National Natural Science Foundation of China(No.32171345)Hebei Provincial Natural Science Foundation of China(No.C2022104003)+2 种基金the Fok Ying Tung Education Foundation(No.141039)the Fund of Key Laboratory of Advanced Materials of Ministry of Education,the International Joint Research Center of Aerospace Biotechnology and Medical Engineering,Ministry of Science and Technology of Chinathe 111 Project(No.B13003).
文摘The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies to diseases such as osteoarthritis.Tissue engineering has been proposed as a promising strategy to meet the demand of simultaneous regeneration of both cartilage and subchondral bone by constructing integrated gradient tissue-engineered osteochondral scaffold(IGTEOS).This review brought forward the main challenges of establishing a satisfactory IGTEOS from the perspectives of the complexity of physiology and microenvironment of osteochondral tissue,and the limitations of obtaining the desired and required scaffold.Then,we comprehensively discussed and summarized the current tissue-engineered efforts to resolve the above challenges,including architecture strategies,fabrication techniques and in vitro/in vivo evaluation methods of the IGTEOS.Especially,we highlighted the advantages and limitations of various fabrication techniques of IGTEOS,and common cases of IGTEOS application.Finally,based on the above challenges and current research progress,we analyzed in details the future perspectives of tissue-engineered osteochondral construct,so as to achieve the perfect reconstruction of the cartilaginous and osseous layers of osteochondral tissue simultaneously.This comprehensive and instructive review could provide deep insights into our current understanding of IGTEOS.
基金supported by the National Science Fund for Distinguished Young Scholars (31625011)the National Key Research and Development Program (2016YFC1101100)+1 种基金the National Key Research and Development Plan Young Scientists Program (2017YFA0106000)the Young Elite Scientists Sponsorship Program by Cast (YESS20160180)
文摘The rapid endothelialization of tissue-engineered blood vessels(TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for the treatment of cardiovascular diseases.β-cyclodextrin sulfate is a type of hollow molecule that has good biocompatibility and anticoagulation properties and exhibits a sustained release of icariin. We studied whether icariin-loaded β-cyclodextrin sulfate can promote the endothelialization of TEBVs. The experimental results showed that icariin could significantly promote the proliferation and migration of endothelial progenitor cells; at the same time, icariin could promote the migration of rat vascular endothelial cells(RAVECs). Subsequently,we used an electrostatic force to modify the surface of the TEBVs with icariin-loaded β-cyclodextrin sulfate, and these vessels were implanted into the rat common carotid artery. After 3 months, micro-CT results showed that the TEBVs modified using icariin-loaded β-cyclodextrin sulfate had a greater patency rate. Scanning electron microscopy(SEM) and CD31 immunofluorescence results showed a better degree of endothelialization. Taken together, icariin-loaded β-cyclodextrin sulfate can achieve anticoagulation and rapid endothelialization of TEBVs to ensure their long-term patency.
基金Project supported by the National Basic Research Program (973) of China (No. 2005CB623902-1)the Science Research Foundation of the Ministry of Health of China (No. WKJ2006-2-2007)
文摘To create a scaffold that is suitable for the construction of tissue-engineered skin, a novel asymmetric porous scaffold with different pore sizes on either side was prepared by combining a collagen-chitosan porous membrane with fibrin glue. Tissue-engineered skin was fabricated using this asymmetric scaffold, fibroblasts, and a human keratinocyte line (HaCaT). Epidermal cells could be seen growing easily and achieved confluence on the fibrin glue on the upper surface of the scaffold. Scanning electron microscopy showed typical shuttle-like fibroblasts adhering to the wall of the scaffold and fluorescence microscopy showed them growing in the dermal layer of the scaffold. The constructed composite skin substitute had a histological structure similar to that of normal skin tissue after three weeks of culture. The results of our study suggest that the asymmetric scaffold is a promising biologically functional material for skin tissue engineering, with prospects for clinical applications.
基金National High Technology Research and Development Program ("863"Program) of China (No.2006AA 02A132)
文摘AIM: To evaluate the biological functions of tissue-engineered human corneal epithelium (TE-HCEP) by corneal transplantation in limbal stem cell deficiency (LSCD) rabbit models. METHODS: TE-HCEPs were reconstructed with DiI-labeled untransfected HCEP cells and denuded amniotic membrane (dAM) in air-liquid interface culture, and their morphology and structure were characterized by hematoxylin-eosin (HE) staining of paraffin-sections, immunohistochemistry and electron microscopy. LSCD models were established by mechanical and alcohol treatment of the left eyes of New Zealand white rabbits, and their eyes were transplanted with TE-HCEPs with dAM surface outside by lamellar keratoplasty (LKP). Corneal transparency, neovascularization, thickness, and epithelial integrality of both traumatic and post transplantation eyes were checked once a week by slit-lamp corneal microscopy, a corneal pachymeter, and periodic acid-Schiff (PAS) staining. At day 120 post surgery, the rabbits in each group were sacrificed and their corneas were examined by DiI label observation, HE staining, immunohistochemistry and electron microscopy. RESULTS: After cultured for 5 days on dAM, HCEP cells, maintaining keratin 3 expression, reconstructed a 6-7 layer TE-HCEP with normal morphology and structure. The traumatic rabbit corneas, entirely opaque, conjunctivalized and with invaded blood vessels, were used as LSCD models for TE-HCEP transplantation. After transplantation, obvious edema was not found in TE-HCEP-transplanted corneas which became more and more transparent, the invaded blood vessels reduced gradually throughout the monitoring period. The corneas decreased to normal thickness on day 25, while those of dAM eyes were over 575 mu m in thickness during the monitoring period. A 45 layer of epithelium consisting of TE-HCEP originated cells attached tightly to the anterior surface of stroma was reconstructed 120 days after TE-HCEP transplantation, which was similar to the normal control eye in morphology and structure. In contrast, intens
基金supported by Shanghai Science Committee Fund for Key Research Project (No. 04JC14012)Fudan University Med-X Fund, China
文摘Background： A major shortcoming in tissue engineered blood vessels （TEBVs） is the lack of healthy and easily attainable smooth muscle cells （SMCs）. Smooth muscle progenitor cells （SPCs）, especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. Methods： SPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV （EGM-2-MV） medium containing platelet-derived growth factoroBB （PDGF BB）. Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell （SOC） phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction （RT-PCR）. The cells were seeded onto the silk fibroin-modified poly（3-hydroxybutyrate-co-3-hydroxyhexanoate） （SF-PHBHHx） scaflblds by 6× 10^4 cells/cm^2 and cultured under the static condition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-（4,5-dimethylthiazol-2-yl）-diphenyltetrazolium bromide （MTT） assay, scanning electron microscope （SEM）, and 4,6-diamidino-2-phenylindole （DAPI） staining. Results： SOCs displayed specific ＂hill and valley＂ morphology, expressed the specific markers of the SMC lineage： smooth muscle （SM） a-actin, calponin and smooth muscle myosin heavy chain （SM MHC） at protein and messenger ribonucleic acid （mRNA） levels. RT-PCR results demonstrate that SOCs also expressed smooth muscle protein 22a （SM22a, a contractile protein, and extracellular matrix components elastin and matrix Gla protein （MGP）, as well as vascular endothelial growth factor （VEGF）. After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation. Conclusion： SPCs isolated from peripheral blood can be differentiated the SMCs in vitro and have an impressive growth potential in the
基金Supported by National High Technology Research and Development Program("863" Program) of China(No.2006AA02A132)
文摘AIM: To demonstrate the morphology and structure of in vitro reconstructed tissue-engineered human corneal epithelium (TE-HCEP) with seeder cells from an untransfected HCEP cell line. METHODS: The TE-HCEPs were reconstructed in vitro with seeder cells from an untransfected HCEP cell line, and scaffold carriers of denuded amniotic membrane (dAM) in air-liquid interface culture for 3, 5, 7 and 9 days, respectively. The specimens were examined with hematoxylin-eosin (HE) staining of paraffin-section, immunocytochemical staining, scanning and transmission electron microscopy. RESULTS: During in vitro reconstruction of TE-HCEP, HCEP cells formed a 3-4, 6-7 and 8-10 layers of an HCEP-like structure on dAMs in air-liquid interface culture for 3, 5 and 7 days, respectively. But the cells deceased to 5-6 layers and the structure of straified epithelium became loose at day 9. And the cells maintained positive expression of marker proteins (keratin 3 and keratin 12), cell-junction proteins (zonula occludens-1, E-cadherin, connexin 43 and integrin beta 1) and membrane transport protein of Na+-K+ ATPase. The HCEP cells in TE-HCEP were rich in microvilli on apical surface and established numerous cell-cell and cell-dAM junctions at day 5. CONCLUSION: The morphology and structure of the reconstructed TE-HCEP were similar to those of HCEP in vivo. The HCEP cells in the reconstructed TE-HCEP maintained the properties of HCEP cells, including abilities of forming intercellular and cell-extracellular matrix junctions and abilities of performing membrane transportation. The untransfected HCEP cells and dAMs could promisingly be used in reconstruction HCEP equivalent for clinical corneal epithelium transplantation.
文摘BACKGROUND Diabetic foot ulcers(DFUs)are common in patients with diabetes,especially those undergoing hemodialysis.In severe cases,these ulcers can cause damage to the lower extremities and lead to amputation.Traditional treatments such as flap transposition and transfemoral amputation are not always applicable in all cases.Therefore,there is a need for alternative treatment methods.CASE SUMMARY This report describes a 62-year-old female patient who was admitted to the hospital with plantar and heel ulcers on her left foot.The patient had a history of renal failure and was undergoing regular hemodialysis.Digital subtraction angiography showed extensive stenosis and occlusion in the left superficial femoral artery,left peroneal artery and left posterior tibial artery.Following evaluation by a multidisciplinary team,the patient was diagnosed with type 2 DFUs(TEXAS 4D).Traditional treatments were deemed unsuitable,and the patient was treated with endovascular surgery in the affected area,in addition to supportive medical treatment,local debridement,and sequential repair using split-thickness skin and tissue-engineered skin grafts combined with negative pressure treatment.After four months,the wound had completely healed,and the patient was able to walk with a walking aid.CONCLUSION This study demonstrates a new treatment method for DFUs was successful,using angioplasty,skin grafts,and negative pressure.
基金Shanghai Municipal Natural Science Foundation,No.06ZR14108
文摘BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological rejections. Cells that do not induce immunological rejections and that are relatively easy to acquire are urgently needed for transplantation. OBJECTIVE： To bridge sciatic nerve defects using tissue engineered nerves constructed with neural tissue-committed stem cells （NTCSCs） derived from bone marrow; to observe morphology and function of rat nerves following bridging; to determine the effect of autologous nerve transplantation, which serves as the gold standard for evaluating efficacy of tissue-engineered nerves. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed in the Anatomical Laboratory and Biomedical Institute of the Second Military Medical University of Chinese PLA between September 2004 and April 2006. MATERIALS： Five Sprague Dawley rats, aged 1 month and weighing 100-150 g, were used for cell culture. Sixty Sprague Dawley rats aged 3 months and weighing 220-250 g, were used to establish neurological defect models. Nestin, neuron-specific enolase （NSE）, glial fibrillary acidic protein （GFAP）, and S-100 antibodies were provided by Santa Cruz Biotechnology, Inc., USA. Acellular nerve grafts were derived from dogs. METHODS： All rats, each with 1-cm gap created in the right sciatic nerve, were randomly assigned to three groups. Each group comprised 20 rats. Autograft nerve transplantation group： the severed 1-cm length nerve segment was reverted, but with the two ends exchanged; the proximal segment was sutured to the distal sciatic nerve stump and the distal segment to the proximal stump. Blank nerve scaffold transplantation group： a 1-cm length acellular nerve graft was used to bridge the sciatic nerve gap. NTCSC engineered nerve transplantation group： a 1-cm length acellular nerve graft, in which NTCSCs were inoculated, was used t
文摘Urethral stricture disease is increasingly common occurring in about 1%of males over the age of 55.The stricture tissue is rich in myofibroblasts and multi-nucleated giant cells which are thought to be related to stricture formation and collagen synthesis.An increase in collagen is associated with the loss of the normal vasculature of the normal urethra.The actual incidence differs based on worldwide populations,geography,and income.The stricture aetiology,location,length and patient’s age and comorbidity are important in deciding the course of treatment.In this review we aim to summarise the existing knowledge of the aetiology of urethral strictures,review current treatment regimens,and present the challenges of using tissue-engineered buccal mucosa(TEBM)to repair scarring of the urethra.In asking this question we are also mindful that recurrent fibrosis occurs in other tissuesdhow can we learn from these other pathologies?
基金Project (Nos.2001AA625050 and 2006AA02A132) supported by the National High-Tech R&D Program (863) of China
文摘To evaluate the therapeutic efficiency of tissue-engineered human corneal endothelia (TE-HCEs) on rabbit primary corneal endotheliopathy (PCEP),TE-HCEs reconstructed with monoclonal human corneal endothelial cells (mcHCECs) and modified denuded amniotic membranes (mdAMs) were transplanted into PCEP models of New Zealand white rabbits using penetrating keratoplasty.The TE-HCEs were examined using diverse techniques including slit-lamp biomicroscopy observation and pachymeter and tonometer measurements in vivo,and fluorescent microscopy,alizarin red staining,paraffin sectioning,scanning and transmission electron microscopy observations in vitro.The corneas of transplanted eyes maintained transparency for as long as 200 d without obvious edema or immune rejection.The corneal thickness of transplanted eyes decreased gradually after transplanting,reaching almost the thickness of normal eyes after 156 d,while the TE-HCE non-transplanted eyes were turbid and showed obvious corneal edema.The polygonal corneal endothelial cells in the transplanted area originated from the TE-HCE transplant.An intact monolayer corneal endothelium had been reconstructed with the morphology,cell density and structure similar to those of normal rabbit corneal endothelium.In conclusion,the transplanted TE-HCE can reconstruct the integrality of corneal endothelium and restore corneal transparency and thickness in PCEP rabbits.The TE-HCE functions normally as an endothelial barrier and pump and promises to be an equivalent of HCE for clinical therapy of human PCEP.
基金This work was supported by the National Key Research and Development Program of China(grant number 2017YFC1104702)the National Natural Science Foundation of China(grant numbers 31600792,31771065).
文摘Treatment of acute and chronic wounds is one of the primary challenges faced by doctors.Bioderived materials have significant potential clinical value in tissue injury treatment and defect reconstruction.Various strategies,including drug loading,addition of metallic element(s),crosslinking and combining two or more distinct types of materials with complementary features,have been used to synthesize more suitable materials for wound healing.In this review,we describe the recent developments made in the processing of bioderived materials employed for cutaneous wound healing,including newly developed materials such as keratin and soy protein.The focus was on the key properties of the bioderived materials that have shown great promise in improving wound healing,restoration and reconstruction.With their good biocompatibility,nontoxic catabolites,microinflammation characteristics,as well as their ability to induce tissue regeneration and reparation,the bioderived materials have great potential for skin tissue repair.
基金Supported by the National Key R&D Program of China (No.2016YFC1100100)the Key R&D Program of Shaanxi Province (No.2018ZDXM-SF-056)+2 种基金the Health and Family Planning Research Fund Project of Shaanxi Province (No.2016C004)the Key Research and Development Program of Shaanxi Province (No.2019SF-196)the Research Talent Project of Xi’an Municipal Health Commission (No.J201902037)。
文摘Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidirectional differentiation potential. A large amount of data confirmed that CS-MSCs can be induced to differentiate into functional keratocytes in vitro, which is the motive force for maintaining corneal transparency and producing a normal corneal stroma. CS-MSCs are also an important component of the limbal microenvironment. Furthermore, they are of great significance in the reconstruction of ocular surface tissue and tissue engineering for active biocornea construction. In this paper, the localization and biological characteristics of CS-MSCs, the use of CS-MSCs to reconstruct a tissue-engineered active biocornea, and the repair of the limbal and matrix microenvironment by CS-MSCs are reviewed, and their application prospects are discussed.
基金supported by The National Science Fund for Outstanding Young Scholars(No:31822021)The Key Research and Development Plan Young Scientists Program(No:2017YFA0106000)+1 种基金The National Key Research and Development Plan(No:2016YFC1101100)National Science Foundation of China(No:31771057).
文摘Tissue-engineered vascular grafts(TEVGs)have enormous potential for vascular replacement therapy.However,thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs(<6 mm)after transplantation.Endothelialization of TEVGs is a key point to prevent thrombosis.Here,we discuss different types of endothelialization and different seed cells of tissue-engineered vascular grafts.Meanwhile,endothelial heterogeneity is also discussed.Based on it,we provide a new perspective for selecting suitable types of endothelialization and suitable seed cells to improve the long-term patency rate of tissue-engineered vascular grafts with different diameters and lengths.
