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
Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds bas...Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.展开更多
Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering application.The present study deals with further improvement in the tensile strength and biological properties of...Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering application.The present study deals with further improvement in the tensile strength and biological properties of this type of scaffold to make it a potential template for bone-tissue regeneration.We experimented with adding 0%–15%(volume fraction)gelatin(GE),a protein-based biopolymer known to promote cell adhesion,proliferation,and differentiation.The resulting tri-polymer complex was used as bioink to fabricate SA/CH/GEmatrices by three-dimensional(3D)printing.Morphological studies using scanning electron microscopy revealed the microfibrous porous architecture of all the structures,which had a pore size range of 383–419μm.X-ray diffraction and Fourier-transform infrared spectroscopy analyses revealed the amorphous nature of the scaffold and the strong electrostatic interactions among the functional groups of the polymers,thereby forming polyelectrolyte complexes which were found to improve mechanical properties and structural stability.The scaffolds exhibited a desirable degradation rate,controlled swelling,and hydrophilic characteristics which are favorable for bone-tissue engineering.The tensile strength improved from(386±15)to(693±15)kPa due to the increased stiffness of SA/CH scaffolds upon addition of gelatin.The enhanced protein adsorption and in vitro bioactivity(forming an apatite layer)confirmed the ability of the SA/CH/GE scaffold to offer higher cellular adhesion and a bone-like environment to cells during the process of tissue regeneration.In vitro biological evaluation including the MTT assay,confocal microscopy analysis,and alizarin red S assay showed a significant increase in cell attachment,cell viability,and cell proliferation,which further improved biomineralization over the scaffold surface.In addition,SA/CH containing 15%gelatin designated as SA/CH/GE15 showed superior performance to the other fabricated 3D structures,demonstrating its potential for use in bone-tissue engineering.展开更多
Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects ...Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of drugs.In this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the samples.Furthermore,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were evaluated.The microstructural observation of the scaffolds reported interconnected pores with 150–300µm in diameter.The 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D scaffolds.SPL release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th day.In addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved significantly.These findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.展开更多
The latest advances in the field of biomaterials have opened new avenues for scientific breakthroughs in tissue engineer-ing which greatly contributed for the successful translation of tissue engineering products into...The latest advances in the field of biomaterials have opened new avenues for scientific breakthroughs in tissue engineer-ing which greatly contributed for the successful translation of tissue engineering products into the market/clinics.Bio-materials are easily processed to become similar to natural extracellular matrix,making them ideal temporary supports for mimicking the three-dimensional(3D)microenvironment required for maintaining the adequate cell/tissue functions both in vitro and in vivo^([1]).展开更多
Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic simila...Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review： nanostructured calcium phosphate cement （CPC）; nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen： （i） nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; （ii） the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; （iii） nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; （iv） combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and （v） cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.展开更多
Given the limited spontaneous repair that follows cartilage injury, demand is growing for tissue engi- neering approaches for cartilage regeneration. There are two major applications for tissue-engineered cartilage. O...Given the limited spontaneous repair that follows cartilage injury, demand is growing for tissue engi- neering approaches for cartilage regeneration. There are two major applications for tissue-engineered cartilage. One is in orthopedic surgery, in which the engineered cartilage is usually used to repair cartilage defects or loss in an articular joint or meniscus in order to restore the joint function. The other is for head and neck reconstruction, in which the engineered cartilage is usually applied to repair cartilage defects or loss in an auricle, trachea, nose, larynx, or eyelid. The challenges faced by the engineered car- tilage for one application are quite different from those faced by the engineered cartilage for the other application. As a result, the emphases of the engineering strategies to generate cartilage are usually quite different for each application. The statuses of preclinical animal investigations and of the clinical translation of engineered cartilage are also at different levels for each application. The aim of this review is to provide an opinion piece on the challenges, current developments, and future directions for cartilage engineering for both applications.展开更多
To explore the possible mechanism of osteogenesis for deciduous teeth stem cells (DTSCs) in vivo/ vitro, stem cells from goat deciduous teeth (SGDs) were firstly isolated, induced and transplanted into immunocompromis...To explore the possible mechanism of osteogenesis for deciduous teeth stem cells (DTSCs) in vivo/ vitro, stem cells from goat deciduous teeth (SGDs) were firstly isolated, induced and transplanted into immunocompromised mice. The SGDs's mineralization pattern and osteogenesis were compared with bone marrow messenchymal stem cells (BMMSCs) from goats. SGDs have similar osteogenic differentiation pattern in vitro and bone-like tissue formation mechanism in vivo to BMMSCs; moreover SGDs have stronger alkaline phosphatase (ALP) gene expression and osteopontin (OPN) gene expression levels than BMMSCs; also SGDs can form more bone-like tissues than BMMSCs when cell-scaffold compounds are transplanted into immunocompromised mice. This pre-clinical study in a large-animal model confirms that DTSCs may be an appropriate source of stem cells in repairing bone defects with tissue engineering.展开更多
The optimization of the scaffolds to provide a suitable matrix and accelerate the regeneration process is vital for bone tissue engineering.However,poor mechanical and biological characteristics remain the primary cha...The optimization of the scaffolds to provide a suitable matrix and accelerate the regeneration process is vital for bone tissue engineering.However,poor mechanical and biological characteristics remain the primary challenges that must be addressed.For example,although bredigite(Br)has shown great potential for application in bone tissue engineering,it easily fails in replacement.In the present work,these challenges are addressed by reinforcing the Br matrix with nanosheets of graphene oxide(rGO)that have been reduced by bovine serum albumin(BSA)in order to enhance the mechanical properties and biological behavior.The reduction of graphene oxide by BSA improves the water stability of the nanosheets and provides an electrostatic interaction between theBSA-rGO nanosheets and theBr particles.The high thermal conductivity of theBSA-rGO nanosheets decreases the porosity of the Br by transferring heat to the core of the tablet.Furthermore,the addition of BSA-rGO nanosheets into the Br matrix enhances the adhesion of G-292 cells on the surface of the tablets.These findings suggest that the tablet consisting of BSA-rGO-reinforced Br has encouraging potential for application in bone tissue engineering.展开更多
The electrospun nanofibrous scaffolds made of proteins and polysaccharides were thought to be able to simulate the structure of natural extracellular matrix well.Silk fibroin(SF)and chitosan(CS)are probably the most w...The electrospun nanofibrous scaffolds made of proteins and polysaccharides were thought to be able to simulate the structure of natural extracellular matrix well.Silk fibroin(SF)and chitosan(CS)are probably the most widely used natural materials in biomedical fields including liver tissue engineering for their good properties and wide variety of sources.The asialoglycoprotein receptors of hepatocyte were reported to specifically recognize and interact with galactose.In this work,a green electrospun SF/galactosylated chitosan(GC)composite nanofibrous scaffold was fabricated and characterized.The data indicated that the addition of GC greatly influenced the spinning effect of SF aqueous solution,and the average diameter of the composite nanofibers was about 520nm.Moreover,the green electrospun SF/GC nanofibrous scaffolds were demonstrated significantly enhancing the adhesion and proliferation of hepatocyte(RH35)according to our data.The present study did a useful exploration on constructing scaffolds for liver regeneration by green electrospinning,and also laid a good foundation for the further applicative research of this green electrospun scaffolds in liver tissue engineering.展开更多
Neurological diseases and injuries present some of the great- est challenges in modern medicine, often causing irrevers- ible and lifelong burdens in the people whom they afflict. Conditions of stroke, traumatic brain...Neurological diseases and injuries present some of the great- est challenges in modern medicine, often causing irrevers- ible and lifelong burdens in the people whom they afflict. Conditions of stroke, traumatic brain injury, spinal cord injury, and neurodegenerative diseases have devastating con- sequences on millions of people each year, and yet there are currently no therapies or interventions that can repair the structure of neural circuits and restore neural tissue function in the brain and spinal cord. Despite the challenges of over- coming these limitations, there are many new approaches under development that hold much promise. Neural tissue engineering aims to restore and influence the function of damaged or diseased neural tissue generally through the use of stem cells and biomaterials. Many types of biomaterials may be implemented in various designs to influence the survival, differentiation, and function of developing stem cells, as well as to guide neurite extension and morphological architecture of cell cultures. Such designs may aim to reca- pitulate the cellular interactions, extracellular matrix char- acteristics, biochemical factors, and sequences of events that occur in neurodevelopment, in addition to supporting cell survival, differentiation, and integration into innate neural tissue.展开更多
The dynamic structures of extracellular matrix regulate cell behaviors by providing three-dimension ecological niche and mechanical cues.Under the progress of both surface patterning and biomaterials,the cues of micro...The dynamic structures of extracellular matrix regulate cell behaviors by providing three-dimension ecological niche and mechanical cues.Under the progress of both surface patterning and biomaterials,the cues of micro-and nanoscale topography on microstructural scaffold biomaterials are increasingly recognized as decisive factors of biomimetic materials.In this review,we provide an overview of the recent progress of biomimetic microstructured scaffolds,including advances in their biomimetic manufacturing technology,functionality,potential applications and future challenges.We highlight recent progress in the fabrication of microstructured scaffold materials with various biological and physicochemical characteristics of native extracellular matrix.The recent key advances of microstructured scaffold for tissue engineering,bio-adhesive,antibacterial and biosensing applications were offered.Eventually,we summarize by offering our perspective on this fast-growing field.展开更多
Osteochondral （OC） lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteo...Osteochondral （OC） lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteoarthritic degenerative changes in the knee. The lack of spontaneous healing and the drawbacks of the current treatments have increased the attention from the scientific community to this issue. Different tissue engineering approaches have been attempted using different polymers and different scaffolds＇ processing. However, the current conventional techniques do not allow the full control over scaffold fabrication, and in this type of approaches, the tuning ability is the key to success in tissue regeneration. In this sense, the researchers have placed their efforts in the development of solid free-form （SFF） techniques. These techniques allow tuning different properties at the micro-macro scale, creating scaffolds with appropriate features for OC tissue engineering. In this review, it is discussed the current SFF techniques used in OC tissue engineering and presented their promising results and current challenges.展开更多
There are large knowledge gaps regarding how to control stem cells growth and differentiation.The limitations of currently available technologies,such as growth factors and/or gene therapies has led to the search of a...There are large knowledge gaps regarding how to control stem cells growth and differentiation.The limitations of currently available technologies,such as growth factors and/or gene therapies has led to the search of alternatives.We explore here how a cell’s epigenome influences determination of cell type,and potential applications in tissue engineering.A prevalent epigenetic modification is the acetylation of DNA core histone proteins.Acetylation levels heavily influence gene transcription.Histone deacetylase (HDAC) enzymes can remove these acetyl groups,leading to the formation of a condensed and more transcriptionally silenced chromatin.Histone deacetylase inhibitors (HDACis) can inhibit these enzymes,resulting in the increased acetylation of histones,thereby affecting gene expression.There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering,potentially providing novel tools to control stem cell fate.This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone,cardiac,neural tissues),including the history,current status and future perspectives of using HDACis for stem cell research and tissue engineering,with particular attention paid to how different HDAC isoforms may be integral to this field.展开更多
Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells （DPSCs） for potential application in tendon tissue engin...Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells （DPSCs） for potential application in tendon tissue engineering. The expression of tendon- related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid （PGA） fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a ootential stem cell source for tissue enEineerin~ of tendon-like tissue.展开更多
The histological analysis of peripheral nerve regeneration is one of the most used methods to demonstrate the success of the regeneration through nerve conduits. Nowadays, it is possible to evaluate different paramete...The histological analysis of peripheral nerve regeneration is one of the most used methods to demonstrate the success of the regeneration through nerve conduits. Nowadays, it is possible to evaluate different parameters of nerve regeneration by using histological, histochemical, immunohistochemical and ultrastructural techniques. The histochemical methods are very sensible and are useful tools to evaluate the extracellular matrix remodeling and the myelin sheath, but they are poorly specific. In contrast, the immunohistochemical methods are highly specific and are frequently used for the identification of the regenerated axons, Sehwann cells and proteins associated to nerve regeneration or neural linage. The ultrastructural techniques offer the possibility to perform a high resolution morphological and quantitative analysis of the nerve regeneration. However, the use of a single histological method may not be enough to assess the degree of regeneration, and the combination of different histological techniques could be necessary.展开更多
It has shown that altering crosslink density of biopolymers will regulate the morphology of Mesenchymal Stem Cells （MSCs） and the subsequent MSCs differentia- tion. These observations have been found in a wide range...It has shown that altering crosslink density of biopolymers will regulate the morphology of Mesenchymal Stem Cells （MSCs） and the subsequent MSCs differentia- tion. These observations have been found in a wide range of biopolymers. However, a recent work published in Nature Materials has revealed that MSCs morphology and differen- tiation was unaffected by crosslink density of polydimethyl- siloxane （PDMS）, which remains elusive. To understand such unusual behaviour, we use nanoindentation tests and modelling to characterize viscoelastic properties and sur- face adhesion of PDMS with different base：crosslink ratio varied from 50：1 （50D） to 10：1 （10D）. It has shown that lower crosslink density leads to lower elastic moduli. De- spite lower nanoindentation elastic moduli, PDMS with lowest crosslink density has higher local surface adhesion which would affect cell-biomaterials interactions. This work suggests that surface adhesion is likely another important physical cue to regulate cell-biomaterials interactions.展开更多
The complex meniscus tissue plays a critical role in the knee. The high susceptibility to injury has led to an intense pursuit for better tissue engineering regenerative strategies, where scaffolds play a major role. ...The complex meniscus tissue plays a critical role in the knee. The high susceptibility to injury has led to an intense pursuit for better tissue engineering regenerative strategies, where scaffolds play a major role. In this study, indirect printed hierarchical multilayered sca ffolds composed by a silk fibroin (SF) upper layer and an 80/20 (w/w) ratio of SF/ionic-doped β-tricalcium phosphate (TCP) bottom layer were developed. Furthermore, a comparative analysis between two types of sca ffolds pro- duced using di fferent SF concentrations, i.e., 8% (w/v) (Hi8) and 16% (w/v) (Hi16) was performed. In terms of architecture and morphology, the produced sca ffolds presented homogeneous porosity in both layers and no di fferences were observed when comparing both sca ffolds. A decrease in terms of mechanical performance of the sca ffolds was observed when SF concentration decreased from 16 to 8% (w/v). Hi16 revealed a static compressive modulus of 0.66 ± 0.05 MPa and dynamical mechanical properties ranging from 2.17 ± 0.25 to 3.19 ± 0.38 MPa. By its turn, Hi8 presented a compressive modulus of 0.27 ± 0.08 MPa and dynamical mechanical properties ranging from 1.03 ± 0.08 MPa to 1.56 ± 0.13 MPa. In vitro bioactivity studies showed formation of apatite crystals onto the surface of Hi8 and Hi16 bottom layers. Human meniscus cells (hMCs) and human primary osteoblasts were cultured separately onto the top layer (SF8 and SF16) and bottom layer (SF8/TCP and SF16/TCP) of the hierarchical sca ffolds Hi8 and Hi16, respectively. Both cell types showed good adhesion and proliferation as denoted by the live/dead staining, Alamar Blue assay and DNA quanti fication analysis. Subcutaneous implantation in mice revealed weak in flammation and sca ffold’s integrity. The hierarchical indirect printed SF sca ffolds can be promising candidate for meniscus TE sca ffolding applications due their suitable mechanical properties, good biological performance and possibility of being applied in a patient-speci fic approach.展开更多
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 National Natural Science Foundation of China(52003113,31900950,82102334,82002313,82072444)the National Key Research&Development Program of China(2018YFC2001502,2018YFB1105705)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(2021A1515010745,2020A1515110356,2023A1515011986)the Shenzhen Fundamental Research Program(JCYJ20190808120405672)the Key Program of the National Natural Science Foundation of Zhejiang Province(LZ22C100001)the Natural Science Foundation of Shanghai(20ZR1469800)the Integration Innovation Fund of Shanghai Jiao Tong University(2021JCPT03),the Science and Technology Projects of Guangzhou City(202102020359)the Zigong Key Science and Technology Plan(2022ZCNKY07).SXC thanks the financial support under the Startup Grant of the University of Chinese Academy of Sciences(WIUCASQD2021026).HW thanks the Futian Healthcare Research Project(FTWS2022013)the financial support of China Postdoctoral Science Foundation(2021TQ0118).SL thanks the financial support of China Postdoctoral Science Foundation(2022M721490).
文摘Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.
基金The authors are thankful to Ministry of Human Resource Development(presently Ministry of Education),Government of India,New Delhi,for providing research facility by sanctioning Center of Excellence(F.No.5-6/2013-TS VII)in Tissue Engineering and Center of Excellence in Orthopedic Tissue Engineering and Rehabilitation funded by World Bank under TEQIP-II.
文摘Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering application.The present study deals with further improvement in the tensile strength and biological properties of this type of scaffold to make it a potential template for bone-tissue regeneration.We experimented with adding 0%–15%(volume fraction)gelatin(GE),a protein-based biopolymer known to promote cell adhesion,proliferation,and differentiation.The resulting tri-polymer complex was used as bioink to fabricate SA/CH/GEmatrices by three-dimensional(3D)printing.Morphological studies using scanning electron microscopy revealed the microfibrous porous architecture of all the structures,which had a pore size range of 383–419μm.X-ray diffraction and Fourier-transform infrared spectroscopy analyses revealed the amorphous nature of the scaffold and the strong electrostatic interactions among the functional groups of the polymers,thereby forming polyelectrolyte complexes which were found to improve mechanical properties and structural stability.The scaffolds exhibited a desirable degradation rate,controlled swelling,and hydrophilic characteristics which are favorable for bone-tissue engineering.The tensile strength improved from(386±15)to(693±15)kPa due to the increased stiffness of SA/CH scaffolds upon addition of gelatin.The enhanced protein adsorption and in vitro bioactivity(forming an apatite layer)confirmed the ability of the SA/CH/GE scaffold to offer higher cellular adhesion and a bone-like environment to cells during the process of tissue regeneration.In vitro biological evaluation including the MTT assay,confocal microscopy analysis,and alizarin red S assay showed a significant increase in cell attachment,cell viability,and cell proliferation,which further improved biomineralization over the scaffold surface.In addition,SA/CH containing 15%gelatin designated as SA/CH/GE15 showed superior performance to the other fabricated 3D structures,demonstrating its potential for use in bone-tissue engineering.
文摘Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of drugs.In this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the samples.Furthermore,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were evaluated.The microstructural observation of the scaffolds reported interconnected pores with 150–300µm in diameter.The 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D scaffolds.SPL release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th day.In addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved significantly.These findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.
基金the financial sup-port provided through the EU-funded ONCOSCREEN project(No.101097036).
文摘The latest advances in the field of biomaterials have opened new avenues for scientific breakthroughs in tissue engineer-ing which greatly contributed for the successful translation of tissue engineering products into the market/clinics.Bio-materials are easily processed to become similar to natural extracellular matrix,making them ideal temporary supports for mimicking the three-dimensional(3D)microenvironment required for maintaining the adequate cell/tissue functions both in vitro and in vivo^([1]).
基金supported by NIH R01 DE14190 and R21 DE22625 (HX)National Science Foundation of China 31100695 and 31328008 (LZ), 81401794 (PW)Maryland Stem Cell Research Fund and University of Maryland School of Dentistry
文摘Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review： nanostructured calcium phosphate cement （CPC）; nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen： （i） nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; （ii） the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; （iii） nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; （iv） combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and （v） cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.
文摘Given the limited spontaneous repair that follows cartilage injury, demand is growing for tissue engi- neering approaches for cartilage regeneration. There are two major applications for tissue-engineered cartilage. One is in orthopedic surgery, in which the engineered cartilage is usually used to repair cartilage defects or loss in an articular joint or meniscus in order to restore the joint function. The other is for head and neck reconstruction, in which the engineered cartilage is usually applied to repair cartilage defects or loss in an auricle, trachea, nose, larynx, or eyelid. The challenges faced by the engineered car- tilage for one application are quite different from those faced by the engineered cartilage for the other application. As a result, the emphases of the engineering strategies to generate cartilage are usually quite different for each application. The statuses of preclinical animal investigations and of the clinical translation of engineered cartilage are also at different levels for each application. The aim of this review is to provide an opinion piece on the challenges, current developments, and future directions for cartilage engineering for both applications.
基金the Science and Technology Commission fund of Shanghai Municipality (No. 09JC1411700)the Collaboration Projects of Development and Research from Basic Science of Stomatology of Shanghai(No. S30206-KF09)the Fund of Shanghai Jiaotong University School of Medicine (No. 09XJ21030)
文摘To explore the possible mechanism of osteogenesis for deciduous teeth stem cells (DTSCs) in vivo/ vitro, stem cells from goat deciduous teeth (SGDs) were firstly isolated, induced and transplanted into immunocompromised mice. The SGDs's mineralization pattern and osteogenesis were compared with bone marrow messenchymal stem cells (BMMSCs) from goats. SGDs have similar osteogenic differentiation pattern in vitro and bone-like tissue formation mechanism in vivo to BMMSCs; moreover SGDs have stronger alkaline phosphatase (ALP) gene expression and osteopontin (OPN) gene expression levels than BMMSCs; also SGDs can form more bone-like tissues than BMMSCs when cell-scaffold compounds are transplanted into immunocompromised mice. This pre-clinical study in a large-animal model confirms that DTSCs may be an appropriate source of stem cells in repairing bone defects with tissue engineering.
基金Thiswork is financially supported by IranUniversity of Science and Technology(IUST)and Motamed Cancer Institute(ACECR).
文摘The optimization of the scaffolds to provide a suitable matrix and accelerate the regeneration process is vital for bone tissue engineering.However,poor mechanical and biological characteristics remain the primary challenges that must be addressed.For example,although bredigite(Br)has shown great potential for application in bone tissue engineering,it easily fails in replacement.In the present work,these challenges are addressed by reinforcing the Br matrix with nanosheets of graphene oxide(rGO)that have been reduced by bovine serum albumin(BSA)in order to enhance the mechanical properties and biological behavior.The reduction of graphene oxide by BSA improves the water stability of the nanosheets and provides an electrostatic interaction between theBSA-rGO nanosheets and theBr particles.The high thermal conductivity of theBSA-rGO nanosheets decreases the porosity of the Br by transferring heat to the core of the tablet.Furthermore,the addition of BSA-rGO nanosheets into the Br matrix enhances the adhesion of G-292 cells on the surface of the tablets.These findings suggest that the tablet consisting of BSA-rGO-reinforced Br has encouraging potential for application in bone tissue engineering.
基金“111 Project”Biomedical Textile Materials Science and Technology,China(No.B07024)Natural Science Foundation of Shanghai,China(No.12ZR1400300)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry
文摘The electrospun nanofibrous scaffolds made of proteins and polysaccharides were thought to be able to simulate the structure of natural extracellular matrix well.Silk fibroin(SF)and chitosan(CS)are probably the most widely used natural materials in biomedical fields including liver tissue engineering for their good properties and wide variety of sources.The asialoglycoprotein receptors of hepatocyte were reported to specifically recognize and interact with galactose.In this work,a green electrospun SF/galactosylated chitosan(GC)composite nanofibrous scaffold was fabricated and characterized.The data indicated that the addition of GC greatly influenced the spinning effect of SF aqueous solution,and the average diameter of the composite nanofibers was about 520nm.Moreover,the green electrospun SF/GC nanofibrous scaffolds were demonstrated significantly enhancing the adhesion and proliferation of hepatocyte(RH35)according to our data.The present study did a useful exploration on constructing scaffolds for liver regeneration by green electrospinning,and also laid a good foundation for the further applicative research of this green electrospun scaffolds in liver tissue engineering.
文摘Neurological diseases and injuries present some of the great- est challenges in modern medicine, often causing irrevers- ible and lifelong burdens in the people whom they afflict. Conditions of stroke, traumatic brain injury, spinal cord injury, and neurodegenerative diseases have devastating con- sequences on millions of people each year, and yet there are currently no therapies or interventions that can repair the structure of neural circuits and restore neural tissue function in the brain and spinal cord. Despite the challenges of over- coming these limitations, there are many new approaches under development that hold much promise. Neural tissue engineering aims to restore and influence the function of damaged or diseased neural tissue generally through the use of stem cells and biomaterials. Many types of biomaterials may be implemented in various designs to influence the survival, differentiation, and function of developing stem cells, as well as to guide neurite extension and morphological architecture of cell cultures. Such designs may aim to reca- pitulate the cellular interactions, extracellular matrix char- acteristics, biochemical factors, and sequences of events that occur in neurodevelopment, in addition to supporting cell survival, differentiation, and integration into innate neural tissue.
文摘The dynamic structures of extracellular matrix regulate cell behaviors by providing three-dimension ecological niche and mechanical cues.Under the progress of both surface patterning and biomaterials,the cues of micro-and nanoscale topography on microstructural scaffold biomaterials are increasingly recognized as decisive factors of biomimetic materials.In this review,we provide an overview of the recent progress of biomimetic microstructured scaffolds,including advances in their biomimetic manufacturing technology,functionality,potential applications and future challenges.We highlight recent progress in the fabrication of microstructured scaffold materials with various biological and physicochemical characteristics of native extracellular matrix.The recent key advances of microstructured scaffold for tissue engineering,bio-adhesive,antibacterial and biosensing applications were offered.Eventually,we summarize by offering our perspective on this fast-growing field.
文摘Osteochondral （OC） lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteoarthritic degenerative changes in the knee. The lack of spontaneous healing and the drawbacks of the current treatments have increased the attention from the scientific community to this issue. Different tissue engineering approaches have been attempted using different polymers and different scaffolds＇ processing. However, the current conventional techniques do not allow the full control over scaffold fabrication, and in this type of approaches, the tuning ability is the key to success in tissue regeneration. In this sense, the researchers have placed their efforts in the development of solid free-form （SFF） techniques. These techniques allow tuning different properties at the micro-macro scale, creating scaffolds with appropriate features for OC tissue engineering. In this review, it is discussed the current SFF techniques used in OC tissue engineering and presented their promising results and current challenges.
基金This work is partly supported by the French CNRS/SPI (programATIP,programIMPRES) ,the Region of Lorraine ,France ,andthe Associa-tion Franco-Chinoise pour la Recherche Scientifique et Technique (PRAB03-06)
基金funded by the EPSRC Centre for Doctoral Training in Tissue Engineering and Regenerative Medicine–Innovation in Medical and Biological Engineeringpartially sponsored by the EU [FP7/ 2007-2013] for ‘SkelGEN’ consortium (n° 318553) and the British Council
文摘There are large knowledge gaps regarding how to control stem cells growth and differentiation.The limitations of currently available technologies,such as growth factors and/or gene therapies has led to the search of alternatives.We explore here how a cell’s epigenome influences determination of cell type,and potential applications in tissue engineering.A prevalent epigenetic modification is the acetylation of DNA core histone proteins.Acetylation levels heavily influence gene transcription.Histone deacetylase (HDAC) enzymes can remove these acetyl groups,leading to the formation of a condensed and more transcriptionally silenced chromatin.Histone deacetylase inhibitors (HDACis) can inhibit these enzymes,resulting in the increased acetylation of histones,thereby affecting gene expression.There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering,potentially providing novel tools to control stem cell fate.This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone,cardiac,neural tissues),including the history,current status and future perspectives of using HDACis for stem cell research and tissue engineering,with particular attention paid to how different HDAC isoforms may be integral to this field.
基金supported by the Natural Science Foundation of China (81171470 and 81100761)the key clinical specialty discipline construction programme of Fujian, Chinathe Key Project of Science and Technology Bureau of Jiangsu Province (BL2013002)
文摘Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells （DPSCs） for potential application in tendon tissue engineering. The expression of tendon- related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid （PGA） fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a ootential stem cell source for tissue enEineerin~ of tendon-like tissue.
文摘The histological analysis of peripheral nerve regeneration is one of the most used methods to demonstrate the success of the regeneration through nerve conduits. Nowadays, it is possible to evaluate different parameters of nerve regeneration by using histological, histochemical, immunohistochemical and ultrastructural techniques. The histochemical methods are very sensible and are useful tools to evaluate the extracellular matrix remodeling and the myelin sheath, but they are poorly specific. In contrast, the immunohistochemical methods are highly specific and are frequently used for the identification of the regenerated axons, Sehwann cells and proteins associated to nerve regeneration or neural linage. The ultrastructural techniques offer the possibility to perform a high resolution morphological and quantitative analysis of the nerve regeneration. However, the use of a single histological method may not be enough to assess the degree of regeneration, and the combination of different histological techniques could be necessary.
基金funded by EPSRC–Newcastle University Sandpit Workshop Award
文摘It has shown that altering crosslink density of biopolymers will regulate the morphology of Mesenchymal Stem Cells （MSCs） and the subsequent MSCs differentia- tion. These observations have been found in a wide range of biopolymers. However, a recent work published in Nature Materials has revealed that MSCs morphology and differen- tiation was unaffected by crosslink density of polydimethyl- siloxane （PDMS）, which remains elusive. To understand such unusual behaviour, we use nanoindentation tests and modelling to characterize viscoelastic properties and sur- face adhesion of PDMS with different base：crosslink ratio varied from 50：1 （50D） to 10：1 （10D）. It has shown that lower crosslink density leads to lower elastic moduli. De- spite lower nanoindentation elastic moduli, PDMS with lowest crosslink density has higher local surface adhesion which would affect cell-biomaterials interactions. This work suggests that surface adhesion is likely another important physical cue to regulate cell-biomaterials interactions.
文摘The complex meniscus tissue plays a critical role in the knee. The high susceptibility to injury has led to an intense pursuit for better tissue engineering regenerative strategies, where scaffolds play a major role. In this study, indirect printed hierarchical multilayered sca ffolds composed by a silk fibroin (SF) upper layer and an 80/20 (w/w) ratio of SF/ionic-doped β-tricalcium phosphate (TCP) bottom layer were developed. Furthermore, a comparative analysis between two types of sca ffolds pro- duced using di fferent SF concentrations, i.e., 8% (w/v) (Hi8) and 16% (w/v) (Hi16) was performed. In terms of architecture and morphology, the produced sca ffolds presented homogeneous porosity in both layers and no di fferences were observed when comparing both sca ffolds. A decrease in terms of mechanical performance of the sca ffolds was observed when SF concentration decreased from 16 to 8% (w/v). Hi16 revealed a static compressive modulus of 0.66 ± 0.05 MPa and dynamical mechanical properties ranging from 2.17 ± 0.25 to 3.19 ± 0.38 MPa. By its turn, Hi8 presented a compressive modulus of 0.27 ± 0.08 MPa and dynamical mechanical properties ranging from 1.03 ± 0.08 MPa to 1.56 ± 0.13 MPa. In vitro bioactivity studies showed formation of apatite crystals onto the surface of Hi8 and Hi16 bottom layers. Human meniscus cells (hMCs) and human primary osteoblasts were cultured separately onto the top layer (SF8 and SF16) and bottom layer (SF8/TCP and SF16/TCP) of the hierarchical sca ffolds Hi8 and Hi16, respectively. Both cell types showed good adhesion and proliferation as denoted by the live/dead staining, Alamar Blue assay and DNA quanti fication analysis. Subcutaneous implantation in mice revealed weak in flammation and sca ffold’s integrity. The hierarchical indirect printed SF sca ffolds can be promising candidate for meniscus TE sca ffolding applications due their suitable mechanical properties, good biological performance and possibility of being applied in a patient-speci fic approach.
