Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to ra...Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.展开更多
The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infan...The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.展开更多
Tissue engineering and regenera-tive medicine have shown signifi-cant potential for repairing and regenerating damaged tissues and can be used to provide personalized treatment plans,with broad applica-tion prospects....Tissue engineering and regenera-tive medicine have shown signifi-cant potential for repairing and regenerating damaged tissues and can be used to provide personalized treatment plans,with broad applica-tion prospects.In this special issue,Bin Li’s team outlines the latest advances in minimally invasive implantable biomaterials for bone regeneration and different methods of achieving osteogenesis,with a focus on bioceramics and polymer materials and their applications in bone healing,vertebral augmenta-tion,implant fixation,tumor treatment of bone,and treatment of infections related to bone defects.Xinquan Jiang’s team constructs a novel photo-responsive multifunctional polyetheretherketone(PEEK)-based implant material(sPEEK/BP/E7)through the self-assembly of black phosphorus(BP)nanoplatelets,bioinspired poly-dopamine(PDA),and the biologically active short peptide E7 on sPEEK.The material exhibits effective osteogenic effects and good sterilization performance,providing a new idea for clinical application.展开更多
The field of bone tissue engineering has experienced an increase in prevalence due to the inherent challenge of the natural regeneration of significant bone deformities.This investigation focused on the preparation of...The field of bone tissue engineering has experienced an increase in prevalence due to the inherent challenge of the natural regeneration of significant bone deformities.This investigation focused on the preparation of Three-Dimensional(3D)-printed Polycaprolactone(PCL)scaffolds with varying proportions of Nanohydroxyapatite(NHA)and Nanoclay(NC),and their physiochemical and biological properties were assessed.The mechanical properties of PCL are satisfactory;however,its hydrophobic nature and long-term degradation hinder its use in scaffold fabrication.NHA and NC have been employed to improve the hydrophilic characteristics,mechanical strength,adhesive properties,biocompatibility,biodegradability,and osteoconductive behavior of PCL.The morphology results demonstrated 3D-printed structures with interconnected rectangular macropores and proper nanoparticle distribution.The sample containing 70 wt%NC showed the highest porosity(65.98±2.54%),leading to an increased degradation rate.The compressive strength ranged from 10.65±1.90 to 84.93±9.93 MPa,which is directly proportional to the compressive strength of cancellous bone(2–12 MPa).The wettability,water uptake,and biodegradability of PCL scaffolds considerably improved as the amount of NC increased.The results of the cellular assays exhibited increased proliferation,viability,and adhesion of MG-63 cells due to the addition of NHA and NC to the scaffolds.Finally,according to the in vitro results,it can be concluded that 3D-printed samples with higher amounts of NC can be regarded as a suitable scaffold for expediting the regeneration process of bone defects.展开更多
Biomedical scaffold fabrication has seen advancements in mimicking the native extracellular matrix through intricate three-dimensional(3D)structures conducive to tissue regeneration.Coiled fibrous scaffolds have emerg...Biomedical scaffold fabrication has seen advancements in mimicking the native extracellular matrix through intricate three-dimensional(3D)structures conducive to tissue regeneration.Coiled fibrous scaffolds have emerged as promising substrates owing to their ability to provide unique topographical cues.In this study,coiled poly(ε-caprolactone)(PCL)fibrous bundles were fabricated using an alginate-based composite system,and processed with 3D printing.The unique structure was obtained through the die-swell phenomenon related to the release of residual stresses from the printed strut,thereby transforming aligned PCL fibers into coiled structures.The effects of printing parameters,such as pneumatic pressure and nozzle moving speed,on fiber morphology were investigated to ensure a consistent formation of coiled PCL fibers.The resulting coiled PCL fibrous scaffold demonstrated higher activation of mechanotransduction signaling as well as upregulation of osteogenic-related genes in human adipose stem cells(hASCs),supporting its potential in bone tissue engineering.展开更多
Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired b...Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.展开更多
Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also ...Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell(SC)cords migration and axons elongation.Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects,systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce.This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration,and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them,encompassing(1)in vitro prevascularization,(2)in vivo prevascularization,and(3)stimulation of neurovascularization in situ.Furthermore,we emphasize that the lack of accuracy for structure and spatiotemporal regulation,as well as the operational inconvenience and delayed connection to the host's nerve stumps,have stuck the existing neurovascularization technology in the preclinical stage.The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.展开更多
In tissue engineering(TE),tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo,thereby inducing endogenous tissue regeneration through top...In tissue engineering(TE),tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo,thereby inducing endogenous tissue regeneration through topological cues.An ideal TE scaffold should possess biomimetic cross-scale structures,similar to that of natural extracellular matrices,at the nano-to macro-scale level.Although freeform fabrication of TE scaffolds can be achieved through 3D printing,this method is limited in simultaneously building multiscale structures.To address this challenge,low-temperature fields were adopted in the traditional fabrication processes,such as casting and 3D printing.Ice crystals grow during scaffold fabrication and act as a template to control the nano-and micro-structures.These microstructures can be optimized by adjusting various parameters,such as the direction and magnitude of the low-temperature field.By preserving the macro-features fabricated using traditional methods,additional micro-structures with smaller scales can be incorporated simultaneously,realizing cross-scale structures that provide a better mimic of natural organs and tissues.In this paper,we present a state-of-the-art review of three low-temperature-field-assisted fabrication methods—freeze casting,cryogenic3D printing,and freeze spinning.Fundamental working principles,fabrication setups,processes,and examples of biomedical applications are introduced.The challenges and outlook for low-temperature-assisted fabrication are also discussed.展开更多
Tissue engineering and regenerative medicine is a new interdisciplinary subject integrating life science,material science,engineering technology,and clinical medicine.Over the last ten years,significant advancements h...Tissue engineering and regenerative medicine is a new interdisciplinary subject integrating life science,material science,engineering technology,and clinical medicine.Over the last ten years,significant advancements have been achieved in the study of biomaterials and tissue engineering.Progress in the field of tissue engineering and regenerative medicine can result in optimal tissue regeneration and effective functional reconstruction.Spinal cord injury(SCI)is the most severe complication of spinal trauma and frequently results in significant functional impairments in the lower extremities of the affected segment.Repair of SCI is a medical challenge worldwide.Advancements in tissue engineering theory and technology offer fresh opportunities for addressing SCI,as well as providing new strategies and methodologies to tackle the challenges associated with repairing and reconstructing spinal cord function.This article provides an overview of the latest developments in tissue engineering and SCI repair,focusing on biomaterials,cells,and active factors.It also introduces nine key components related to SCI and proposes innovative approaches for repairing and functionally reconstructing the injured spinal cord.展开更多
The feasibility of using gene therapy to treat full-thickness articular cartilage defects was investigated with respect to the transfection and expression of exogenous transforming growth factor(TGF)-β_(1)genes in bo...The feasibility of using gene therapy to treat full-thickness articular cartilage defects was investigated with respect to the transfection and expression of exogenous transforming growth factor(TGF)-β_(1)genes in bone marrow-derived mesenchymal stem cells(MSCs)in vitro.The full-length rat TGF-β_(1)cDNA was transfected to MSCs mediated by lipofectamine and then selected with G418,a synthetic neomycin analog.The transient and stable expression of TGF-β_(1)by MSCs was detected by using immunohistochemical staining.The lipofectamine-mediated gene therapy efficiently transfected MSCs in vitro with the TGF-β_(1)gene causing a marked up-regulation in TGF-β_(1)expression as compared with the vector-transfected control groups,and the increased expression persisted for at least 4 weeks after selected with G418.It was suggested that bone marrow-derived MSCs were susceptible to in vitro lipofectamine mediated TGF-β_(1)gene transfer and that transgene expression persisted for at least 4 weeks.Having successfully combined the existing techniques of tissue engineering with the novel possibilities offered by modern gene transfer technology,an innovative concept,i.e.molecular tissue engineering,are put forward for the first time.As a new branch of tissue engineering,it represents both a new area and an important trend in research.Using this technique,we have a new powerful tool with which:(1)to modify the functional biology of articular tissue repair along defined pathways of growth and differentiation and(2)to affect a better repair of full-thickness articular cartilage defects that occur as a result of injury and osteoarthritis.展开更多
The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basi...The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF β 1 gene at different doses was transduced into the rat bone marrow derived MSCs to examine the effects of TGF β 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 μl lipofectamine mediated 1 μg TGF β 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine=1μg/3μl), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3 H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF β 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.展开更多
Tissue engineering has confronted many difficulties mainly as follows:1)How to modulate the adherence,proliferation,and oriented differentiation of seed cells, especially that of stemcells. 2) Massive preparation and ...Tissue engineering has confronted many difficulties mainly as follows:1)How to modulate the adherence,proliferation,and oriented differentiation of seed cells, especially that of stemcells. 2) Massive preparation and sustained controllable delivery of tissue inducing factors or plasmid DNA, such as growth factors, angiogenesis stimulators,and so on. 3) Development of 'intelligent biomimetic materials' as extracellular matrix with a good superficial and structural compatibility as well as biological activity to stimulate predictable, controllable and desirable responses under defined conditions.Molecular biology is currently one of the most exciting fields of research across life sciences,and the advances in it also bring a bright future for tissue engineering to overcome these difficulties.In recent years,tissue engineering benefits a lot from molecular biology.Only a comprehensive understanding of the involved ingredients of tissue engineering (cells,tissue inducing factors,genes,biomaterials) and the subtle relationships between them at molecular level can lead to a successful manipulation of reparative processes and a better biological substitute.Molecular tissue engineering,the offspring of the tissue engineering and molecular biology,has gained an increasing importance in recent years.It offers the promise of not simply replacing tissue,but improving the restoration.The studies presented in this article put forward this new concept for the first time and provide an insight into the basic principles,status and challenges of this emerging technology.展开更多
Cartilage and facial muscle tissue provide basic yet vital functions for homeostasis throughout the body, making human survival and function highly dependent upon these somatic components. When cartilage and facial mu...Cartilage and facial muscle tissue provide basic yet vital functions for homeostasis throughout the body, making human survival and function highly dependent upon these somatic components. When cartilage and facial muscle tissues are harmed or completely destroyed due to disease, trauma, or any other degenerative process, homeostasis and basic body functions consequently become negatively affected. Although most cartilage and cells can regenerate themselves after any form of the aforementioned degenerative disease or trauma, the highly specific characteristics of facial muscles and the specific structures of the cells and tissues required for the proper function cannot be exactly replicated by the body itself. Thus, some form of cartilage and bone tissue engineering is necessary for proper regeneration and function. The use of progenitor cells for this purpose would be very beneficial due to their highly adaptable capabilities, as well as their ability to utilize a high diffusion rate, making them ideal for the specific nature and functions of cartilage and facial muscle tissue. Going along with this, once the progenitor cells are obtained, applying them to a scaffold within the oral cavity in the affected location allows them to adapt to the environment and create cartilage or facial muscle tissue that is specific to the form and function of the area. The principal function of the cartilage and tissue is vascularization, which requires a specific form that allows them to aid the proper flow of bodily functions related to the oral cavity such as oxygen flow and removal of waste. Facial muscle is also very thin, making its reproduction much more possible. Taking all these into consideration, this review aims to highlight and expand upon the primary benefits of the cartilage and facial muscle tissue engineering and regeneration, focusing on how these processes are performed outside of and within the body.展开更多
The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical te...The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.展开更多
Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone l...Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors(GFs), it makes stem cells the ideal agents for bone regeneration.Furthermore, platelet-rich plasma(PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future.展开更多
Peripheral nerve injury is a common clinical problem and affects the quality of life of patients. Traditional restoration methods are not satisfactory. Researchers increasingly focus on the field of tissue engineering...Peripheral nerve injury is a common clinical problem and affects the quality of life of patients. Traditional restoration methods are not satisfactory. Researchers increasingly focus on the field of tissue engineering. The three key points in establishing a tissue engineering material are the biological scaffold material, the seed cells and various growth factors. Understanding the type of nerve injury, the construction of scaffold and the process of repair are necessary to solve peripheral nerve injury and promote its regeneration. This review describes the categories of peripheral nerve injury, fundamental research of peripheral nervous tissue engineering and clinical research on peripheral nerve scaffold material, and paves a way for related research and the use of conduits in clinical practice.展开更多
Endothelial cells (TEC_3 cells) derived from mouse embryonic stem (ES) cells were used as seed cells to construct blood vessels. Tissue engineered blood vessels were made by seeding 8 × 10~6 smooth muscle cells (...Endothelial cells (TEC_3 cells) derived from mouse embryonic stem (ES) cells were used as seed cells to construct blood vessels. Tissue engineered blood vessels were made by seeding 8 × 10~6 smooth muscle cells (SMCs) obtained from rabbit arteries onto a sheet of nonwoven polyglycolic acid (PGA) fibers, which was used as a biodegradable polymer scaffold. After being cultured in DMEM medium for 7 days in vitro, SMCs grew well on the PGA fibers, and the cell-PGA sheet was then wrapped around a silicon tube, and implanted subcutaneously into nude mice. After 6～8 weeks, the silicon tube was replaced with another silicon tube in smaller diameter, and then the TEC_3 cells (endothelial cells differentiated from mouse ES cells) were injected inside the engineered vessel tube as the test group. In the control group only culture medium was injected. Five days later, the engineered vessels were harvested for gross observation, histological and immunohistochemical analysis. The preliminary results demonstrated that the SMC-PGA construct could form a tubular structure in 6～8 weeks and PGA fibers were completely degraded. Histological and immunohistochemical analysis of the newly formed tissue revealed a typical blood vessel structure, including a lining of endothelial cells (ECs) on the lumimal surface and the presence of SMC and collagen in the wall. No EC lining was found in the tubes of control group. Therefore, the ECs differentiated from mouse ES cells can serve as seed cells for endothelium lining in tissue engineered blood vessels.展开更多
An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,...An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,biomaterials,tissue engineering,and regenerative medicine.The cell microenvironment consists of not only its surrounding cells and soluble factors,but also its extracellular matrix(ECM)or nearby external biomaterials in tissue engineering and regeneration.This review focuses on six aspects of bioma-terial-related cell microenvironments:①chemical composition of materials,②material dimensions and architecture,③material-controlled cell geometry,④effects of material charges on cells,⑤matrix stiff-ness and biomechanical microenvironment,and⑥surface modification of materials.The present chal-lenges in tissue engineering are also mentioned,and eight perspectives are predicted.展开更多
Gelatin/Alginate hydrogels were engineered for bioplotting in tissue engineering.One major drawback of hydrogel scaffolds is the lack of adequate mechanical properties.In this study,using a bioplotter,we constructed t...Gelatin/Alginate hydrogels were engineered for bioplotting in tissue engineering.One major drawback of hydrogel scaffolds is the lack of adequate mechanical properties.In this study,using a bioplotter,we constructed the scaffolds with different pore architectures by deposition of gelatin/alginate hydrogels layerby-layer.The scaffolds with different crosslinking degree were obtained by post-crosslinking methods.Their physicochemical properties,as well as cell viability,were assessed.Different crosslinking methods had little influence on scaffold architecture,porosity,pore size and distribution.By contrast,the water absorption ability,degradation rate and mechanical properties of the scaffolds were dramatically affected by treatment with various concentrations of crosslinking agent(glutaraldehyde).The crosslinking process using glutaraldehyde markedly improved the stability and mechanical strength of the hydrogel scaf-folds.Besides the post-processing methods,the pore architecture can also evidently affect the mechanical properties of the scaffolds.The crosslinked gelatin/alginate scaffolds showed a good potential to encap-sulate cells or drugs.展开更多
基金funded by the Israeli Ministry of Innovation,Science and Technology(Grant No.3-11873)the Israel Science Foundation(Grant No.1563/10)+1 种基金the Randy L.and Melvin R.Berlin Family Research Center for Regenerative Medicinethe Gurwin Family Foundation.
文摘Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.
文摘The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.
文摘Tissue engineering and regenera-tive medicine have shown signifi-cant potential for repairing and regenerating damaged tissues and can be used to provide personalized treatment plans,with broad applica-tion prospects.In this special issue,Bin Li’s team outlines the latest advances in minimally invasive implantable biomaterials for bone regeneration and different methods of achieving osteogenesis,with a focus on bioceramics and polymer materials and their applications in bone healing,vertebral augmenta-tion,implant fixation,tumor treatment of bone,and treatment of infections related to bone defects.Xinquan Jiang’s team constructs a novel photo-responsive multifunctional polyetheretherketone(PEEK)-based implant material(sPEEK/BP/E7)through the self-assembly of black phosphorus(BP)nanoplatelets,bioinspired poly-dopamine(PDA),and the biologically active short peptide E7 on sPEEK.The material exhibits effective osteogenic effects and good sterilization performance,providing a new idea for clinical application.
文摘The field of bone tissue engineering has experienced an increase in prevalence due to the inherent challenge of the natural regeneration of significant bone deformities.This investigation focused on the preparation of Three-Dimensional(3D)-printed Polycaprolactone(PCL)scaffolds with varying proportions of Nanohydroxyapatite(NHA)and Nanoclay(NC),and their physiochemical and biological properties were assessed.The mechanical properties of PCL are satisfactory;however,its hydrophobic nature and long-term degradation hinder its use in scaffold fabrication.NHA and NC have been employed to improve the hydrophilic characteristics,mechanical strength,adhesive properties,biocompatibility,biodegradability,and osteoconductive behavior of PCL.The morphology results demonstrated 3D-printed structures with interconnected rectangular macropores and proper nanoparticle distribution.The sample containing 70 wt%NC showed the highest porosity(65.98±2.54%),leading to an increased degradation rate.The compressive strength ranged from 10.65±1.90 to 84.93±9.93 MPa,which is directly proportional to the compressive strength of cancellous bone(2–12 MPa).The wettability,water uptake,and biodegradability of PCL scaffolds considerably improved as the amount of NC increased.The results of the cellular assays exhibited increased proliferation,viability,and adhesion of MG-63 cells due to the addition of NHA and NC to the scaffolds.Finally,according to the in vitro results,it can be concluded that 3D-printed samples with higher amounts of NC can be regarded as a suitable scaffold for expediting the regeneration process of bone defects.
基金supported by the‘Korea National Institute of Health’research project(2022ER130502)a grant from by SMC-SKKU Future Convergence Academic Research Program,2024supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2024-00336758)。
文摘Biomedical scaffold fabrication has seen advancements in mimicking the native extracellular matrix through intricate three-dimensional(3D)structures conducive to tissue regeneration.Coiled fibrous scaffolds have emerged as promising substrates owing to their ability to provide unique topographical cues.In this study,coiled poly(ε-caprolactone)(PCL)fibrous bundles were fabricated using an alginate-based composite system,and processed with 3D printing.The unique structure was obtained through the die-swell phenomenon related to the release of residual stresses from the printed strut,thereby transforming aligned PCL fibers into coiled structures.The effects of printing parameters,such as pneumatic pressure and nozzle moving speed,on fiber morphology were investigated to ensure a consistent formation of coiled PCL fibers.The resulting coiled PCL fibrous scaffold demonstrated higher activation of mechanotransduction signaling as well as upregulation of osteogenic-related genes in human adipose stem cells(hASCs),supporting its potential in bone tissue engineering.
基金financially supported by the National Natural Science Foundation of China(Nos.52103184 and 8226030956)the National Key Research and Development Program of China(No.2022YFC2407503)+3 种基金Key Project of the Natural Science Basic Research Plan of Shaanxi Province(No.2022JZ43)Natural Science Basic Research Program of Shaanxi Province(No.2024JCYBQN-0874)Medical Research Key Project of Xi'an Science and Technology Bureau(No.2024JH-YXZD-0055)Medical Research Project of Xi'an Science and Technology Bureau(No.22YXYJ0083)
文摘Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.
基金financially supported by the following programs:National Key Research and Development Program of China(No.2023YFB3813003)National Natural Science Foundation of China(Nos.82430031,82122014,82071085)+1 种基金Zhejiang Provincial Natural Science Foundation of China(No.LR21H140001)the Central Universities(No.2022FZZX01-33)。
文摘Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell(SC)cords migration and axons elongation.Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects,systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce.This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration,and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them,encompassing(1)in vitro prevascularization,(2)in vivo prevascularization,and(3)stimulation of neurovascularization in situ.Furthermore,we emphasize that the lack of accuracy for structure and spatiotemporal regulation,as well as the operational inconvenience and delayed connection to the host's nerve stumps,have stuck the existing neurovascularization technology in the preclinical stage.The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.
基金National Natural Science Foundation Council of China(Grant No.52305359)Hubei Provincial Natural Science Foundation of China(Grant No.2023AFB141)National Medical Products Administration Key Laboratory for Dental Materials(PKUSS20240401)。
文摘In tissue engineering(TE),tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo,thereby inducing endogenous tissue regeneration through topological cues.An ideal TE scaffold should possess biomimetic cross-scale structures,similar to that of natural extracellular matrices,at the nano-to macro-scale level.Although freeform fabrication of TE scaffolds can be achieved through 3D printing,this method is limited in simultaneously building multiscale structures.To address this challenge,low-temperature fields were adopted in the traditional fabrication processes,such as casting and 3D printing.Ice crystals grow during scaffold fabrication and act as a template to control the nano-and micro-structures.These microstructures can be optimized by adjusting various parameters,such as the direction and magnitude of the low-temperature field.By preserving the macro-features fabricated using traditional methods,additional micro-structures with smaller scales can be incorporated simultaneously,realizing cross-scale structures that provide a better mimic of natural organs and tissues.In this paper,we present a state-of-the-art review of three low-temperature-field-assisted fabrication methods—freeze casting,cryogenic3D printing,and freeze spinning.Fundamental working principles,fabrication setups,processes,and examples of biomedical applications are introduced.The challenges and outlook for low-temperature-assisted fabrication are also discussed.
基金supported by grants from the National Natural Science Foundation of China(92368207)the Chinese Academy of Engineering(2023-SBZD-11)the Natural Science Foundation of Jiangsu Province(BK20232023).
文摘Tissue engineering and regenerative medicine is a new interdisciplinary subject integrating life science,material science,engineering technology,and clinical medicine.Over the last ten years,significant advancements have been achieved in the study of biomaterials and tissue engineering.Progress in the field of tissue engineering and regenerative medicine can result in optimal tissue regeneration and effective functional reconstruction.Spinal cord injury(SCI)is the most severe complication of spinal trauma and frequently results in significant functional impairments in the lower extremities of the affected segment.Repair of SCI is a medical challenge worldwide.Advancements in tissue engineering theory and technology offer fresh opportunities for addressing SCI,as well as providing new strategies and methodologies to tackle the challenges associated with repairing and reconstructing spinal cord function.This article provides an overview of the latest developments in tissue engineering and SCI repair,focusing on biomaterials,cells,and active factors.It also introduces nine key components related to SCI and proposes innovative approaches for repairing and functionally reconstructing the injured spinal cord.
文摘The feasibility of using gene therapy to treat full-thickness articular cartilage defects was investigated with respect to the transfection and expression of exogenous transforming growth factor(TGF)-β_(1)genes in bone marrow-derived mesenchymal stem cells(MSCs)in vitro.The full-length rat TGF-β_(1)cDNA was transfected to MSCs mediated by lipofectamine and then selected with G418,a synthetic neomycin analog.The transient and stable expression of TGF-β_(1)by MSCs was detected by using immunohistochemical staining.The lipofectamine-mediated gene therapy efficiently transfected MSCs in vitro with the TGF-β_(1)gene causing a marked up-regulation in TGF-β_(1)expression as compared with the vector-transfected control groups,and the increased expression persisted for at least 4 weeks after selected with G418.It was suggested that bone marrow-derived MSCs were susceptible to in vitro lipofectamine mediated TGF-β_(1)gene transfer and that transgene expression persisted for at least 4 weeks.Having successfully combined the existing techniques of tissue engineering with the novel possibilities offered by modern gene transfer technology,an innovative concept,i.e.molecular tissue engineering,are put forward for the first time.As a new branch of tissue engineering,it represents both a new area and an important trend in research.Using this technique,we have a new powerful tool with which:(1)to modify the functional biology of articular tissue repair along defined pathways of growth and differentiation and(2)to affect a better repair of full-thickness articular cartilage defects that occur as a result of injury and osteoarthritis.
基金This project was supported by a grant from NationalNatural Science Foundation of China (No. 30 170 2 70 )
文摘The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF β 1 gene at different doses was transduced into the rat bone marrow derived MSCs to examine the effects of TGF β 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 μl lipofectamine mediated 1 μg TGF β 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine=1μg/3μl), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3 H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF β 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.
文摘Tissue engineering has confronted many difficulties mainly as follows:1)How to modulate the adherence,proliferation,and oriented differentiation of seed cells, especially that of stemcells. 2) Massive preparation and sustained controllable delivery of tissue inducing factors or plasmid DNA, such as growth factors, angiogenesis stimulators,and so on. 3) Development of 'intelligent biomimetic materials' as extracellular matrix with a good superficial and structural compatibility as well as biological activity to stimulate predictable, controllable and desirable responses under defined conditions.Molecular biology is currently one of the most exciting fields of research across life sciences,and the advances in it also bring a bright future for tissue engineering to overcome these difficulties.In recent years,tissue engineering benefits a lot from molecular biology.Only a comprehensive understanding of the involved ingredients of tissue engineering (cells,tissue inducing factors,genes,biomaterials) and the subtle relationships between them at molecular level can lead to a successful manipulation of reparative processes and a better biological substitute.Molecular tissue engineering,the offspring of the tissue engineering and molecular biology,has gained an increasing importance in recent years.It offers the promise of not simply replacing tissue,but improving the restoration.The studies presented in this article put forward this new concept for the first time and provide an insight into the basic principles,status and challenges of this emerging technology.
基金Acknowledgements The authors would like to thank the financial supports from Delta Dental, Osteo Science Foundation （Peter Geistlich Award）, Marquette Innovation Fund, AFOSR （FA9550-12-1-0225） and NSF （EEC-1160483, ECCS-1351533 and CMMI-1363485）.
文摘Cartilage and facial muscle tissue provide basic yet vital functions for homeostasis throughout the body, making human survival and function highly dependent upon these somatic components. When cartilage and facial muscle tissues are harmed or completely destroyed due to disease, trauma, or any other degenerative process, homeostasis and basic body functions consequently become negatively affected. Although most cartilage and cells can regenerate themselves after any form of the aforementioned degenerative disease or trauma, the highly specific characteristics of facial muscles and the specific structures of the cells and tissues required for the proper function cannot be exactly replicated by the body itself. Thus, some form of cartilage and bone tissue engineering is necessary for proper regeneration and function. The use of progenitor cells for this purpose would be very beneficial due to their highly adaptable capabilities, as well as their ability to utilize a high diffusion rate, making them ideal for the specific nature and functions of cartilage and facial muscle tissue. Going along with this, once the progenitor cells are obtained, applying them to a scaffold within the oral cavity in the affected location allows them to adapt to the environment and create cartilage or facial muscle tissue that is specific to the form and function of the area. The principal function of the cartilage and tissue is vascularization, which requires a specific form that allows them to aid the proper flow of bodily functions related to the oral cavity such as oxygen flow and removal of waste. Facial muscle is also very thin, making its reproduction much more possible. Taking all these into consideration, this review aims to highlight and expand upon the primary benefits of the cartilage and facial muscle tissue engineering and regeneration, focusing on how these processes are performed outside of and within the body.
文摘The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases,and National Institute of Dental and Craniofacial Research under Award Numbers AR061052,AR066101 and DE023105 to S.Y
文摘Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors(GFs), it makes stem cells the ideal agents for bone regeneration.Furthermore, platelet-rich plasma(PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future.
基金supported by the National Natural Science Foundation of China,No.31040043,31671248(to NH),No.81171146,81372044,30971526(to BGJ)the Chinese National Ministry of Science and Technology(973 Project),No.2014CB542201(to PXZ)+4 种基金the Ministry of Education Innovation Team,China,No.IRT1201(to PXZ)the Fostering Young Scholars of Peking University Health Science Center,China,No.BMU2017PY013(to PXZ)the Chinese National General Program of National Natural Science Fund,China(to PXZ)the Beijing City Science&Technology New Star Cross Project,China,No.2018019(to PXZ)the National Natural Science Foundation of China,No.31771322,31571235,51373023,21171019,31640045,31571236,31471144,31100860,31371210(to PXZ)
文摘Peripheral nerve injury is a common clinical problem and affects the quality of life of patients. Traditional restoration methods are not satisfactory. Researchers increasingly focus on the field of tissue engineering. The three key points in establishing a tissue engineering material are the biological scaffold material, the seed cells and various growth factors. Understanding the type of nerve injury, the construction of scaffold and the process of repair are necessary to solve peripheral nerve injury and promote its regeneration. This review describes the categories of peripheral nerve injury, fundamental research of peripheral nervous tissue engineering and clinical research on peripheral nerve scaffold material, and paves a way for related research and the use of conduits in clinical practice.
基金supported by the national“973”tissue engineering project of China(G1999054300)Shanghai Science and Technology Development Foundation(03DJ14021)
文摘Endothelial cells (TEC_3 cells) derived from mouse embryonic stem (ES) cells were used as seed cells to construct blood vessels. Tissue engineered blood vessels were made by seeding 8 × 10~6 smooth muscle cells (SMCs) obtained from rabbit arteries onto a sheet of nonwoven polyglycolic acid (PGA) fibers, which was used as a biodegradable polymer scaffold. After being cultured in DMEM medium for 7 days in vitro, SMCs grew well on the PGA fibers, and the cell-PGA sheet was then wrapped around a silicon tube, and implanted subcutaneously into nude mice. After 6～8 weeks, the silicon tube was replaced with another silicon tube in smaller diameter, and then the TEC_3 cells (endothelial cells differentiated from mouse ES cells) were injected inside the engineered vessel tube as the test group. In the control group only culture medium was injected. Five days later, the engineered vessels were harvested for gross observation, histological and immunohistochemical analysis. The preliminary results demonstrated that the SMC-PGA construct could form a tubular structure in 6～8 weeks and PGA fibers were completely degraded. Histological and immunohistochemical analysis of the newly formed tissue revealed a typical blood vessel structure, including a lining of endothelial cells (ECs) on the lumimal surface and the presence of SMC and collagen in the wall. No EC lining was found in the tubes of control group. Therefore, the ECs differentiated from mouse ES cells can serve as seed cells for endothelium lining in tissue engineered blood vessels.
基金the financial support from the National Natural Science Foundation of China (21961160721 and 52130302)the National Key Research and Development Program of China(2016YFC1100300)
文摘An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,biomaterials,tissue engineering,and regenerative medicine.The cell microenvironment consists of not only its surrounding cells and soluble factors,but also its extracellular matrix(ECM)or nearby external biomaterials in tissue engineering and regeneration.This review focuses on six aspects of bioma-terial-related cell microenvironments:①chemical composition of materials,②material dimensions and architecture,③material-controlled cell geometry,④effects of material charges on cells,⑤matrix stiff-ness and biomechanical microenvironment,and⑥surface modification of materials.The present chal-lenges in tissue engineering are also mentioned,and eight perspectives are predicted.
基金supported by the National Basic Research Program of China(“973 Program”,No.2012CB619100)the National Natural Science Foundation of China(Grant No.51372085)+1 种基金the Guangdong–Hongkong Common Technology Bidding Project(No.2013B010136003)the Postdoctoral Science Foundation of China(No.2013M542172)
文摘Gelatin/Alginate hydrogels were engineered for bioplotting in tissue engineering.One major drawback of hydrogel scaffolds is the lack of adequate mechanical properties.In this study,using a bioplotter,we constructed the scaffolds with different pore architectures by deposition of gelatin/alginate hydrogels layerby-layer.The scaffolds with different crosslinking degree were obtained by post-crosslinking methods.Their physicochemical properties,as well as cell viability,were assessed.Different crosslinking methods had little influence on scaffold architecture,porosity,pore size and distribution.By contrast,the water absorption ability,degradation rate and mechanical properties of the scaffolds were dramatically affected by treatment with various concentrations of crosslinking agent(glutaraldehyde).The crosslinking process using glutaraldehyde markedly improved the stability and mechanical strength of the hydrogel scaf-folds.Besides the post-processing methods,the pore architecture can also evidently affect the mechanical properties of the scaffolds.The crosslinked gelatin/alginate scaffolds showed a good potential to encap-sulate cells or drugs.
