Synthetic grafting needs improvements to eliminate secondary surgeries for the removal of implants after healing of the defected tissues.Tissue scaffolds are engineered to serve as temporary templates,which support th...Synthetic grafting needs improvements to eliminate secondary surgeries for the removal of implants after healing of the defected tissues.Tissue scaffolds are engineered to serve as temporary templates,which support the affected tissue and gradually degrade through the healing period.Beside mechanical function to withstand the anatomic loading conditions,scaffolds should also provide a decent biological function for the diffusion of nutrients and oxygen to the cells,and excretion of the wastes from the cells to promote the new tissue growth and vascularization.Moreover,the degradation byproducts of the scaffolds should be safe to the human body.Development of such multifunctional scaffolds requires selection of the right material,design,and manufacturing method.Mg has been recognized as the prominent biodegradable metal with regards to its mechanical properties matching to that of human bone,degradability in the body fluid,and its ability to stimulate new tissue growth.Scaffolds with intricate porous structures can be designed according to the patient-specific anatomic data using computer aided designs.Additive manufacturing(AM)is the right method to materialize these models rapidly with reasonably acceptable range of dimensional accuracy.Thus,the recent research trend is to develop ideal scaffolds using biodegradable Mg through AM methods.This review compiles and discusses the available literature on the AM of biodegradable Mg parts from the viewpoints of material compositions,process conditions,formation quality,dimensional accuracy,microstructure,biodegradation,and mechanical properties.The current achievements are summarized together,and future research directions are identified to promote clinical applications of biodegradable Mg through the advancement of AM.展开更多
Mesenchymal stem cells (MSCs) show the great promise for the treatment of a variety of diseases because of their self-renewal and multipotential abilities. MSCs are generally cultured on two-dimensional (2D) subst...Mesenchymal stem cells (MSCs) show the great promise for the treatment of a variety of diseases because of their self-renewal and multipotential abilities. MSCs are generally cultured on two-dimensional (2D) substrate in vitro. There are indications that they may simultaneously lose their sternness and multipotentiality as the result of prolonged 2D culture. In this study, we used three-dimensional (3D) collagen scaffolds as rat MSCs cartier and compared the properties of MSCs on 3D collagen scaffolds with monolayer cultured MSCs. The results demonstrated that collagen scaffolds were suitable for rat MSCs adherence and proliferation. More importantly, compared to MSCs under 2D culture, 3D MSCs significantly maintained higher expression levels of stemness genes (Oct4, Sox2, Rex-1 and Nanog), yielded high frequencies of colony-forming units-fibroblastic (CFU-F) and showed enhanced osteogenic and adipogenic differentiation efficiency upon induction. Thus, 3D collagen scaffolds may be beneficial for expanding rat MSCs while maintaining the stem cell properties in vitro.展开更多
This study aimed to examine the differences in the morphological properties and proliferation of olfactory ensheathing cells in three-dimensional culture on collagen-heparan sulfate biological scaffolds and in two-dim...This study aimed to examine the differences in the morphological properties and proliferation of olfactory ensheathing cells in three-dimensional culture on collagen-heparan sulfate biological scaffolds and in two-dimensional culture on common flat culture plates. The proliferation rate of olfactory ensheathing cells in three-dimensional culture was higher than that in two-dimensional culture, as detected by an M-I-r assay. In addition, more than half of the olfactory ensheathing cells subcultured using the trypsinization method in three-dimensional culture displayed a spindly Schwann cell-like morphology with extremely long processes, while they showed a flat astrocyte-like morphology in two-dimensional culture. Moreover, spindle-shaped olfactory ensheathing cells tended to adopt an elongated bipolar morphology under both culture conditions. Experimental findings indicate that the morphological properties and proliferation of olfactory ensheathing cells in three-dimensional culture on collagen-heparan sulfate biological scaffolds are better than those in two-dimensional culture.展开更多
Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to crea...Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer- aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine.展开更多
Biodegradable magnesium(Mg)-based medical devices have revolutionized medical implants by uniquely combining biocompatibility and mechanical strength.Fully degradable Mg-based implants have been developed to provide t...Biodegradable magnesium(Mg)-based medical devices have revolutionized medical implants by uniquely combining biocompatibility and mechanical strength.Fully degradable Mg-based implants have been developed to provide temporary structural support and serve as a dynamic scaffold for tissue repair and restructuring.Additionally,Mg-based devices can respond to physiological signals,and their integration with electrical currents or pulses has been explored to enhance tissue healing and functional recovery.This review provides a comprehensive overview of the development and application of Mg-based medical devices,highlighting their evolution from traditional orthopedic,vascular,and dental uses to advanced systems that actively modulate physiological processes—a shift from passive support to active modulation.The application range of Mg-based devices has expanded from early vascular sutures,bone screws,and stents to multiple clinical fields including porous bone repair scaffolds,anastomotic staples,bioactive devices,and electro-active systems.Bioactive Mg devices demonstrate therapeutic properties including antibacterial,anti-inflammatory,anti-tumor,and osteogenic functions through their degradation products,while electro-active devices utilize the electrical properties of Mg for sensing,monitoring,and therapeutic stimulation.Finally,this review highlights current challenges,including maintaining mechanical support performance,optimizing control of biochemical reactions,and balancing electroregulatory functions,and identifies future research directions aimed at enhancing the clinical application of biodegradable Mg-based implants,thereby contributing to the significant advancement in the biomedical field.展开更多
Autologous tissue engineering using biodegradable scaffolds as a carrier is a well-known procedure for penile girth enhancement. We evaluated a group of previously treated patients with the aim to analyze histomorphom...Autologous tissue engineering using biodegradable scaffolds as a carrier is a well-known procedure for penile girth enhancement. We evaluated a group of previously treated patients with the aim to analyze histomorphometric changes after tissue remodeling and to estimate the benefits of repeated procedure. Between February 2012 and December 2016, a group of 21 patients, aged 22-37 (mean 28.0) years, underwent a repeated penile girth enhancement procedure with biodegradable scaffolds. Procedure included insertion of two poly-lactic-co-glycolic acid scaffolds seeded with laboratory-prepared fibroblasts from scrotal tissue specimens. During this procedure, biopsy specimens of tissue formed after the first surgery were taken for microscopic analysis. The mean follow-up was 38 months. Connective tissue with an abundance of connective tissue fibers, small blood vessels, and inflammatory cells were observed in all analyzed surgically removed tissue. Ultrastructural analysis of these tissue samples discovered the presence of large quantities of collagen fibrils running parallel to each other, forming bundles, with a few widely spread fibroblasts. In total, the mean values of flaccid and erect gain in girth after the second surgery were 1.1 ± 0.4 (range: 0.6- 1.7) cm and 1.0±0.3 (range: 0.6-1.5) cm, respectively. Microscopic evaluation of newly formed tissue, induced by autologous tissue engineering using biodegradable scaffolds, showed the presence of vascularized loose connective tissue with an abundance of collagen fibers, fibroblasts, and inflammatory cells, indicating active neovascularization and fibrinogenesis. The benefit of the repeated enhancement procedure was statistically significant.展开更多
A facile approach to construct ferroferric oxide/chitosan composite scaffolds with three-dimensional oriented structure has been explored in this research. Chitosan and ferroferric oxide are co-precipitated by using a...A facile approach to construct ferroferric oxide/chitosan composite scaffolds with three-dimensional oriented structure has been explored in this research. Chitosan and ferroferric oxide are co-precipitated by using an in situ precipitation method, and then lyophilized to get the composite scaffolds. XRD indicated that Fe304 was generated during the gel formation process, and increasing the content of magnetic particles could destruct the crystal structure of chitosan. When the content of magnetic particles is lower than 10%, the layer-by-layer structure and wheel spoke structure are coexisting in the scaffolds. Increasing the content of magnetic particles, just layer-by-layer structure could be observed in the scaffolds. Ferroferric oxide particles were uniformly distributed in the matrix, the size of which was about 0.48 gm in diameter, 2 gm in length. Porosity of magnetic chitosan composite scaffolds is about 90%. When the ratio of ferroferric oxide to chitosan is 5/100, the compressive strength of the material is 0.4367 MPa, which is much higher than that of pure chitosan scaffolds, indicating that the layer-by-layer and wheel spokes complex structure is beneficial for the improvement of the mechanical properties of chitosan scaffolds. However, increasing the content of ferroferric oxide, the compressive strength of scaffolds decreased, because of the decreasing of chitosan crystallization and aggregation of magnetic particles as stress centralized body. Another reason is that the layer-by-layer and wheel spokes complex structure makes bigger contributions for the compressive strength than the layer-by-layer structure does. Three-dimensional ferroferric oxide/chitosan scaffolds could be used as hyperthermia generator system, improving the local circulation of blood, promoting the aggradation of calcium salt and stimulating bone tissue regeneration.展开更多
Zn-based materials are promising as bone repair materials,but their poor mechanical property and bioactivity as well as low degradation rate render the potential application.Rational structural and material design can...Zn-based materials are promising as bone repair materials,but their poor mechanical property and bioactivity as well as low degradation rate render the potential application.Rational structural and material design can address the concerns.In this study,porous Zn-1 wt.%Mg-3 vol.%β-TCP scaffolds with 40%and 60%preset porosities were fabricated via heating-press sintering using NaCl particles as space holders,and their mechanical properties,in vitro degradation behavior,cytotoxicity and in vivo osteogenic activities were evaluated.The results showed that the actual porosities of the scaffolds were 22%and 50%.Mg exists in the form of Zn 2 Mg and Zn 11 Mg 2,whileβ-TCP evenly distributed in the matrix.The compressive yield strength of scaffolds ranges from approximately 58.46 to 71.04 MPa,which is close to that of cancellous bone.The in vitro degradation tests showed that the corrosion rate of the scaffolds was in the range of about 2.73-4.28 mm y^(-1).Moreover,the scaffolds not only provided great space for osteoblasts adhesion and proliferation in vitro but also possessed favorable degradability and osteogenic activity in vivo.The porous Zn-1 wt.%Mg-3 vol.%β-TCP scaffolds manifest reliable mechanical properties,desirable degradability,and osteogenic activity,which are promising as next-generation bone repair materials.展开更多
Tissue engineering’s main goal is to regenerate or replace tissues or organs that have been destroyed by disease,injury,or congenital disabilities.Tissue engineering now uses artificial supporting structures called s...Tissue engineering’s main goal is to regenerate or replace tissues or organs that have been destroyed by disease,injury,or congenital disabilities.Tissue engineering now uses artificial supporting structures called scaffolds to restore damaged tissues and organs.These are utilized to attach the right cells and then grow them.Rapid prototyping appears to be the most promising technology due to its high level of precision and control.Bone tissue replacement“scaffolding”is a common theme discussed in this article.The fused deposition technique was used to construct our scaffold,and a polymer called polylactic acids and soybean oil resin were used to construct our samples.The samples were then divided into two groups;the first group was left without immersion in the simulated body fluid and served as a control for comparison.The second group was immersed in the simulated body fluid.The results of the Field Emission Scanning Electron Microscope(FESEM),Energy Dispersive X-ray Spectroscopy(EDX)and X-ray diffraction(XRD)were utilized to interpret the surface attachment to ions,elements,and compounds,giving us a new perspective on scaffold architecture.In this study,an innovative method has been used to print therapeutic scaffold that combines fused deposition three-dimensional printing with ultraviolet curing to create a high-quality biodegradable polymeric scaffold.Finally,the results demonstrate that adding soybean oil resin to the PLA increased ion attachment to the surface while also attracting tricalcium phosphate formation on the surface of the scaffold,which is highly promising in bone tissue replacement.In conclusion,the soybean oil resin,which is new in the field of bone tissue engineering,shows magnificent characteristics and is a good replacement biopolymer that replaces many ceramic and polymeric materials used in this field that have poor morphological characteristics.展开更多
Due to their capability of fabricating geometrically complex structures,additive manufacturing(AM)techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg al...Due to their capability of fabricating geometrically complex structures,additive manufacturing(AM)techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys,which exhibit appropriate mechanical properties and outstanding biocompatibility.However,many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants,such as the difficulty of Mg powder preparation,powder splash,and crack formation during the AM process.In the present work,the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed.A novel Mg-based alloy(Mg-Nd-Zn-Zr alloy,JDBM)powder with a smooth surface and good roundness was first synthesized successfully,and the AM parameters for Mg-based alloys were optimized.Based on the optimized parameters,porous JDBM scaffolds with three different architectures(biomimetic,diamond,and gyroid)were then fabricated by selective laser melting(SLM),and their mechanical properties and degradation behavior were evaluated.Finally,the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate(DCPD)coating treatment,which greatly suppressed the degradation rate and increased the cytocompatibility,indicating a promising prospect for clinical application as bone tissue engineering scaffolds.展开更多
Three-dimensional(3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover,these models bridge the ga...Three-dimensional(3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover,these models bridge the gap between traditional two-dimensional(2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition,3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models.展开更多
The biodegradability and biocompatibility of porous Mg-2Zn(mass fraction, %) scaffolds coated with nano hydroxyapatite(HAP) were investigated. The nano HAP coating on Mg-2Zn scaffolds was prepared by the pulse ele...The biodegradability and biocompatibility of porous Mg-2Zn(mass fraction, %) scaffolds coated with nano hydroxyapatite(HAP) were investigated. The nano HAP coating on Mg-2Zn scaffolds was prepared by the pulse electrodeposition method. The as-deposited scaffolds were then post-treated with alkaline solution to improve the biodegradation behavior and biocompatibility for implant applications. The microstructure and composition of scaffold and nano HAP coating, as well as their degradation and cytotoxicity behavior in simulated body fluid(SBF) were investigated. The post-treated coating is composed of needle-like HAP with the diameter less than 100 nm developed almost perpendicularly to the substrate, which exhibits a similar composition to natural bone. It is found that the products of immersion in SBF are identified to be HAP,(Ca,Mg)3(PO4)2 and Mg(OH)2. The bioactivity, biocompatibility and cell viabilities for the as-coated and post-treated scaffold extracts are higher than those for the uncoated scaffold. MG63 cells are found to adhere and proliferate on the surface of the as-coated and post-treated scaffolds, making it a promising choice for medical application. The results show that the pulse electrodeposition of nano HAP coating and alkaline treatment is a useful approach to improve the biodegradability and bioactivity of porous Mg-Zn scaffolds.展开更多
Porous calcium phosphate ceramics were produced by compression molding using a special mold followed by sintering. The porous calcium phosphate ceramics have three-dimensional and penetrated open pores 380-400μm in...Porous calcium phosphate ceramics were produced by compression molding using a special mold followed by sintering. The porous calcium phosphate ceramics have three-dimensional and penetrated open pores 380-400μm in diacneter spaced at intervals of 200μm. The layers of the linear penetration pores alternately lay perpendicular to pore direction. The porosity was 59%-65% . The Ca/ P molar ratios of the porous calcium phos phate ceramics range from 1.5 to 1.85. A binder cantaining methyl cellulose was most effective for preparing the powder compact among vinyl acetate, polyvinyl alcohol, starch, stearic acid, methyl cellulose and their mixtures . Stainless steel, polystyrene, nylon and bamboo were used as the long columnar dies for the penetrated open pores. When polystyrene, nylon and bamboo were used as the long columnar male dies, the dies were burned oat during the sintering process. Using stainless steel as the male dies with the removal of the dies before heat treatment resulted in a higher level of densification of the calcium phosphate ceramic.展开更多
The authors regret that the given names and family names of all authors in original article were inadvertently switched.The correct order of the given and family names is provided in this document.Rodriguez-Jimenez Fr...The authors regret that the given names and family names of all authors in original article were inadvertently switched.The correct order of the given and family names is provided in this document.Rodriguez-Jimenez Francisco Javier,Artero-Castro Ana,Studenovska Hana,Selles Francisca,Arteaga Claramunt Alba Maria,Brymova Anna,Jendelova Pavla,Motlik Jan,Petrovski Goran,Lytvynchuk Lyubomyr,Ardan Taras,TichotováLucie,DrutovičSaskia,Sharma Ruchi,Lukovic Dunja,Bharti Kapil,Erceg Slaven.The authors apologize for any inconvenience this may have caused.展开更多
The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have...The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have been performed to design and develop suitable scaffolds for spinal cord regeneration, keeping in mind that the reconstruction of a pro-regenerative environment is the key challenge for an effective neurogenesis. The aim of this review is to outline the main features of an ideal scaffold, based on biomaterials, produced by the electrospinning technique and intended for the spinal cord regeneration. An overview of the poly- mers more investigated in the production of neural fibrous scaffolds is also provided.展开更多
Three-dimensional porous poly-lactic acid(PLA) scaffold was fabricated using fused deposition modeling(FDM) method including 30%, 50% and 70% nominal porosity. Study of phases in initial polymeric material and printed...Three-dimensional porous poly-lactic acid(PLA) scaffold was fabricated using fused deposition modeling(FDM) method including 30%, 50% and 70% nominal porosity. Study of phases in initial polymeric material and printed scaffolds was done by X-ray diffraction(XRD), and no significant phase difference was observed due to the manufacturing process, and the poly-lactic acid retains its crystalline properties. The results of the mechanical properties evaluation by the compression test show that the mechanical properties of the scaffold have decreased significantly with increasing the porosity of scaffold. The microstructure of scaffolds were studied by scanning electron microscope(SEM), showing that the pores had a regular arrangement and their morphology changed with porosity change. The mechanical properties of the poly-lactic acid scaffolds printed using fused deposition modeling, can be adapted to the surrounding tissue, by porosity change.展开更多
Porous biodegradable Mg and its alloys are considered to have a great potential to serve as ideal bone substitutes.The recent progress in additive manufacturing(AM) has prompted its application to fabricate Mg scaffol...Porous biodegradable Mg and its alloys are considered to have a great potential to serve as ideal bone substitutes.The recent progress in additive manufacturing(AM) has prompted its application to fabricate Mg scaffolds with geometrically ordered porous structures.Extrusionbased AM,followed by debinding and sintering,has been recently demonstrated as a powerful approach to fabricating such Mg scaffolds,which can avoid some crucial problems encountered when applying powder bed fusion AM techniques.However,such pure Mg scaffolds exhibit a too high rate of in vitro biodegradation.In the present research,alloying through a pre-alloyed Mg-Zn powder was ultilized to enhance the corrosion resistance and mechanical properties of AM geometrically ordered Mg-Zn scaffolds simultaneously.The in vitro biodegradation behavior,mechanical properties,and electrochemical response of the fabricated Mg-Zn scaffolds were evaluated.Moreover,the response of preosteoblasts to these scaffolds was systematically evaluated and compared with their response to pure Mg scaffolds.The Mg-Zn scaffolds with a porosity of 50.3% and strut density of 93.1% were composed of the Mg matrix and MgZn2second phase particles.The in vitro biodegradation rate of the Mg-Zn scaffolds decreased by 81% at day 1,as compared to pure Mg scaffolds.Over 28 days of static immersion in modified simulated body fluid,the corrosion rate of the Mg-Zn scaffolds decreased from 2.3± 0.9 mm/y to 0.7±0.1 mm/y.The yield strength and Young’s modulus of the Mg-Zn scaffolds were about 3 times as high as those of pure Mg scaffolds and remained within the range of those of trabecular bone throughout the biodegradation tests.Indirect culture of MC3T3-E1 preosteoblasts in Mg-Zn extracts indicated favorable cytocompatibility.In direct cell culture,some cells could spread and form filopodia on the surface of the Mg-Zn scaffolds.Overall,this study demonstrates the great potential of the extrusion-based AM Mg-Zn scaffolds to be further developed as biodegradable bone-substituting biomaterials.展开更多
The biodegradable substitution materials for bone tissue engineering have been a research hotspot.As is known to all,the biodegradability,biocompatibility,mechanical properties and plasticity of the substitution mater...The biodegradable substitution materials for bone tissue engineering have been a research hotspot.As is known to all,the biodegradability,biocompatibility,mechanical properties and plasticity of the substitution materials are the important indicators for the application of implantation materials.In this article,we reported a novel binary substitution material by blending the poly(lactic-acid)-co-(trimethylenecarbonate)and poly(glycolic-acid)-co-(trimethylene-carbonate),which are both biodegradable polymers with the same segment of flexible trimethylene-carbonate in order to accelerate the degradation rate of poly(lactic-acid)-co-(trimethylene carbonate)substrate and improve its mechanical properties.Besides,we further fabricate the porous poly(lactic-acid)-co-(trimethylene-carbonate)/poly(glycolic-acid)-co-(trimethylene-carbonate)scaffolds with uniform microstructure by the 3D extrusion printing technology in a mild printing condition.The physicochemical properties of the poly(lactic-acid)-co-(trimethylenecarbonate)/poly(glycolic-acid)-co-(trimethylene-carbonate)and the 3D printing scaffolds were investigated by universal tensile dynamometer,fourier transform infrared reflection(FTIR),scanning electron microscope(SEM)and differential scanning calorimeter(DSC).Meanwhile,the degradability of the PLLATMC/GA-TMC was performed in vitro degradation assays.Compared with PLLA-TMC group,PLLA-TMC/GATMC groups maintained the decreasing Tg,higher degradation rate and initial mechanical performance.Furthermore,the PLLA-TMC/GA-TMC 3D printing scaffolds provided shape-memory ability at 37℃.In summary,the PLLA-TMC/GA-TMC can be regarded as an alternative substitution material for bone tissue engineering.展开更多
A new method of fabricating porous polymer scaffolds was developed, using sodium hydrogen carbonate particulates as the porogen to foam. The pore structure of polymer scaffolds can easily be manipulated by controlling...A new method of fabricating porous polymer scaffolds was developed, using sodium hydrogen carbonate particulates as the porogen to foam. The pore structure of polymer scaffolds can easily be manipulated by controlling the size and weight fraction of sodium hydrogen carbonate particulates. The scaffolds are highly porous with a porosity greater than 90% and with a larger pore size ranging from 100-400μm, and are well distributed with the interconnected and open pore wall structure which is necessary for tissue engineering. We investigated the effect of the porosity of scaffolds, the pore size of scaffolds and material of polymer on the mechanical properties of scaffolds. The scaffolds fabricated by the method have more big pores than those by the convenient method of salt leaching.展开更多
Objective To investigate the possibility to fabricate a blood vessel scaffold with a combined polymer for tissue engineering. Methods A blood vessel scaffold was designed with a combined polymer composed of rabbit vas...Objective To investigate the possibility to fabricate a blood vessel scaffold with a combined polymer for tissue engineering. Methods A blood vessel scaffold was designed with a combined polymer composed of rabbit vascular smooth muscle cells ( VSMCs), collagen and a non-spinning fabric mesh of polyglycolic acid(PGA). VSMQ were implanted into collagen gel and their growth was observed. The mixed solution of VSMQ and collagen was dropped into the tubular scaffold, followed by 7-day culturing. Results VSMQ formed many prominences after culturing in gelatinous collagen for 3 - 4 hours. With cells extending, some cells became shuttle-or spindle-shaped. After VSMQ-collagen complex was implanted into the PGA mesh, most of VSMCs remained in the pore of PGA mesh with the formation of gelation. VSMCs could adhere to and grow on the PGA fiber. Conclusion The non-spinning PGA porous biodegradable material coated with collagen is a good carrier for VSMCs to adhere and grow. 5 refs,3 figs.展开更多
文摘Synthetic grafting needs improvements to eliminate secondary surgeries for the removal of implants after healing of the defected tissues.Tissue scaffolds are engineered to serve as temporary templates,which support the affected tissue and gradually degrade through the healing period.Beside mechanical function to withstand the anatomic loading conditions,scaffolds should also provide a decent biological function for the diffusion of nutrients and oxygen to the cells,and excretion of the wastes from the cells to promote the new tissue growth and vascularization.Moreover,the degradation byproducts of the scaffolds should be safe to the human body.Development of such multifunctional scaffolds requires selection of the right material,design,and manufacturing method.Mg has been recognized as the prominent biodegradable metal with regards to its mechanical properties matching to that of human bone,degradability in the body fluid,and its ability to stimulate new tissue growth.Scaffolds with intricate porous structures can be designed according to the patient-specific anatomic data using computer aided designs.Additive manufacturing(AM)is the right method to materialize these models rapidly with reasonably acceptable range of dimensional accuracy.Thus,the recent research trend is to develop ideal scaffolds using biodegradable Mg through AM methods.This review compiles and discusses the available literature on the AM of biodegradable Mg parts from the viewpoints of material compositions,process conditions,formation quality,dimensional accuracy,microstructure,biodegradation,and mechanical properties.The current achievements are summarized together,and future research directions are identified to promote clinical applications of biodegradable Mg through the advancement of AM.
基金supported by the grants from the Ministry of Science and Technology of China(Nos.2011CB965001 and 2011CB710905)the Knowledge Innovation Program of the Chinese Academy of Sciences(Nos.KSCX2-YW-R-232, KJCX2-YW-L08 and KYQY-QN-015)
文摘Mesenchymal stem cells (MSCs) show the great promise for the treatment of a variety of diseases because of their self-renewal and multipotential abilities. MSCs are generally cultured on two-dimensional (2D) substrate in vitro. There are indications that they may simultaneously lose their sternness and multipotentiality as the result of prolonged 2D culture. In this study, we used three-dimensional (3D) collagen scaffolds as rat MSCs cartier and compared the properties of MSCs on 3D collagen scaffolds with monolayer cultured MSCs. The results demonstrated that collagen scaffolds were suitable for rat MSCs adherence and proliferation. More importantly, compared to MSCs under 2D culture, 3D MSCs significantly maintained higher expression levels of stemness genes (Oct4, Sox2, Rex-1 and Nanog), yielded high frequencies of colony-forming units-fibroblastic (CFU-F) and showed enhanced osteogenic and adipogenic differentiation efficiency upon induction. Thus, 3D collagen scaffolds may be beneficial for expanding rat MSCs while maintaining the stem cell properties in vitro.
基金sponsored by the National Natural Science Foundation of China,No. 30570628,30770751 and 81171089
文摘This study aimed to examine the differences in the morphological properties and proliferation of olfactory ensheathing cells in three-dimensional culture on collagen-heparan sulfate biological scaffolds and in two-dimensional culture on common flat culture plates. The proliferation rate of olfactory ensheathing cells in three-dimensional culture was higher than that in two-dimensional culture, as detected by an M-I-r assay. In addition, more than half of the olfactory ensheathing cells subcultured using the trypsinization method in three-dimensional culture displayed a spindly Schwann cell-like morphology with extremely long processes, while they showed a flat astrocyte-like morphology in two-dimensional culture. Moreover, spindle-shaped olfactory ensheathing cells tended to adopt an elongated bipolar morphology under both culture conditions. Experimental findings indicate that the morphological properties and proliferation of olfactory ensheathing cells in three-dimensional culture on collagen-heparan sulfate biological scaffolds are better than those in two-dimensional culture.
基金supported by the National Natural Science Foundation of China,No.81301050,81401067,81271392,81471275,81541034the Natural Science Foundation of Tianjin City of China,No.14JCQNJC10200,15JCQNJC11100,16JCYBJC27600
文摘Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer- aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine.
文摘Biodegradable magnesium(Mg)-based medical devices have revolutionized medical implants by uniquely combining biocompatibility and mechanical strength.Fully degradable Mg-based implants have been developed to provide temporary structural support and serve as a dynamic scaffold for tissue repair and restructuring.Additionally,Mg-based devices can respond to physiological signals,and their integration with electrical currents or pulses has been explored to enhance tissue healing and functional recovery.This review provides a comprehensive overview of the development and application of Mg-based medical devices,highlighting their evolution from traditional orthopedic,vascular,and dental uses to advanced systems that actively modulate physiological processes—a shift from passive support to active modulation.The application range of Mg-based devices has expanded from early vascular sutures,bone screws,and stents to multiple clinical fields including porous bone repair scaffolds,anastomotic staples,bioactive devices,and electro-active systems.Bioactive Mg devices demonstrate therapeutic properties including antibacterial,anti-inflammatory,anti-tumor,and osteogenic functions through their degradation products,while electro-active devices utilize the electrical properties of Mg for sensing,monitoring,and therapeutic stimulation.Finally,this review highlights current challenges,including maintaining mechanical support performance,optimizing control of biochemical reactions,and balancing electroregulatory functions,and identifies future research directions aimed at enhancing the clinical application of biodegradable Mg-based implants,thereby contributing to the significant advancement in the biomedical field.
文摘Autologous tissue engineering using biodegradable scaffolds as a carrier is a well-known procedure for penile girth enhancement. We evaluated a group of previously treated patients with the aim to analyze histomorphometric changes after tissue remodeling and to estimate the benefits of repeated procedure. Between February 2012 and December 2016, a group of 21 patients, aged 22-37 (mean 28.0) years, underwent a repeated penile girth enhancement procedure with biodegradable scaffolds. Procedure included insertion of two poly-lactic-co-glycolic acid scaffolds seeded with laboratory-prepared fibroblasts from scrotal tissue specimens. During this procedure, biopsy specimens of tissue formed after the first surgery were taken for microscopic analysis. The mean follow-up was 38 months. Connective tissue with an abundance of connective tissue fibers, small blood vessels, and inflammatory cells were observed in all analyzed surgically removed tissue. Ultrastructural analysis of these tissue samples discovered the presence of large quantities of collagen fibrils running parallel to each other, forming bundles, with a few widely spread fibroblasts. In total, the mean values of flaccid and erect gain in girth after the second surgery were 1.1 ± 0.4 (range: 0.6- 1.7) cm and 1.0±0.3 (range: 0.6-1.5) cm, respectively. Microscopic evaluation of newly formed tissue, induced by autologous tissue engineering using biodegradable scaffolds, showed the presence of vascularized loose connective tissue with an abundance of collagen fibers, fibroblasts, and inflammatory cells, indicating active neovascularization and fibrinogenesis. The benefit of the repeated enhancement procedure was statistically significant.
基金financially supported by the National Natural Science Foundation of China(Nos.21104067 and 50773070)China Postdoctoral Science Foundation(No.20100480085)+1 种基金Key Basic Research Development Plan(973) of China (No.2009CB930104)Grand Science and Technology Special Project of Zhejiang Province(No.2008C11087)
文摘A facile approach to construct ferroferric oxide/chitosan composite scaffolds with three-dimensional oriented structure has been explored in this research. Chitosan and ferroferric oxide are co-precipitated by using an in situ precipitation method, and then lyophilized to get the composite scaffolds. XRD indicated that Fe304 was generated during the gel formation process, and increasing the content of magnetic particles could destruct the crystal structure of chitosan. When the content of magnetic particles is lower than 10%, the layer-by-layer structure and wheel spoke structure are coexisting in the scaffolds. Increasing the content of magnetic particles, just layer-by-layer structure could be observed in the scaffolds. Ferroferric oxide particles were uniformly distributed in the matrix, the size of which was about 0.48 gm in diameter, 2 gm in length. Porosity of magnetic chitosan composite scaffolds is about 90%. When the ratio of ferroferric oxide to chitosan is 5/100, the compressive strength of the material is 0.4367 MPa, which is much higher than that of pure chitosan scaffolds, indicating that the layer-by-layer and wheel spokes complex structure is beneficial for the improvement of the mechanical properties of chitosan scaffolds. However, increasing the content of ferroferric oxide, the compressive strength of scaffolds decreased, because of the decreasing of chitosan crystallization and aggregation of magnetic particles as stress centralized body. Another reason is that the layer-by-layer and wheel spokes complex structure makes bigger contributions for the compressive strength than the layer-by-layer structure does. Three-dimensional ferroferric oxide/chitosan scaffolds could be used as hyperthermia generator system, improving the local circulation of blood, promoting the aggradation of calcium salt and stimulating bone tissue regeneration.
基金supported by the Key Research and Development Program of Shanxi Province(No.202102130501007)the Central Leading Science and Technology Development Foundation of Shanxi Province(No.YDZJSX2021A019)+1 种基金the Natural Science Foundation of Shanxi Province(Nos.202103021223102 and 202203021211173)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(Nos.2021SX-AT008 and 2021SX-AT009).
文摘Zn-based materials are promising as bone repair materials,but their poor mechanical property and bioactivity as well as low degradation rate render the potential application.Rational structural and material design can address the concerns.In this study,porous Zn-1 wt.%Mg-3 vol.%β-TCP scaffolds with 40%and 60%preset porosities were fabricated via heating-press sintering using NaCl particles as space holders,and their mechanical properties,in vitro degradation behavior,cytotoxicity and in vivo osteogenic activities were evaluated.The results showed that the actual porosities of the scaffolds were 22%and 50%.Mg exists in the form of Zn 2 Mg and Zn 11 Mg 2,whileβ-TCP evenly distributed in the matrix.The compressive yield strength of scaffolds ranges from approximately 58.46 to 71.04 MPa,which is close to that of cancellous bone.The in vitro degradation tests showed that the corrosion rate of the scaffolds was in the range of about 2.73-4.28 mm y^(-1).Moreover,the scaffolds not only provided great space for osteoblasts adhesion and proliferation in vitro but also possessed favorable degradability and osteogenic activity in vivo.The porous Zn-1 wt.%Mg-3 vol.%β-TCP scaffolds manifest reliable mechanical properties,desirable degradability,and osteogenic activity,which are promising as next-generation bone repair materials.
文摘Tissue engineering’s main goal is to regenerate or replace tissues or organs that have been destroyed by disease,injury,or congenital disabilities.Tissue engineering now uses artificial supporting structures called scaffolds to restore damaged tissues and organs.These are utilized to attach the right cells and then grow them.Rapid prototyping appears to be the most promising technology due to its high level of precision and control.Bone tissue replacement“scaffolding”is a common theme discussed in this article.The fused deposition technique was used to construct our scaffold,and a polymer called polylactic acids and soybean oil resin were used to construct our samples.The samples were then divided into two groups;the first group was left without immersion in the simulated body fluid and served as a control for comparison.The second group was immersed in the simulated body fluid.The results of the Field Emission Scanning Electron Microscope(FESEM),Energy Dispersive X-ray Spectroscopy(EDX)and X-ray diffraction(XRD)were utilized to interpret the surface attachment to ions,elements,and compounds,giving us a new perspective on scaffold architecture.In this study,an innovative method has been used to print therapeutic scaffold that combines fused deposition three-dimensional printing with ultraviolet curing to create a high-quality biodegradable polymeric scaffold.Finally,the results demonstrate that adding soybean oil resin to the PLA increased ion attachment to the surface while also attracting tricalcium phosphate formation on the surface of the scaffold,which is highly promising in bone tissue replacement.In conclusion,the soybean oil resin,which is new in the field of bone tissue engineering,shows magnificent characteristics and is a good replacement biopolymer that replaces many ceramic and polymeric materials used in this field that have poor morphological characteristics.
基金This work was supported by the National Natural Science Foundation of China(51571143)the National Key Research and Development Program of China(2016YFC1102103)+1 种基金the Science and Technology Commission of Shanghai Municipality(19441906300,18441908000,and 17440730700)San-Ming Project of Medicine in Shenzhen(SZSM201612092).
文摘Due to their capability of fabricating geometrically complex structures,additive manufacturing(AM)techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys,which exhibit appropriate mechanical properties and outstanding biocompatibility.However,many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants,such as the difficulty of Mg powder preparation,powder splash,and crack formation during the AM process.In the present work,the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed.A novel Mg-based alloy(Mg-Nd-Zn-Zr alloy,JDBM)powder with a smooth surface and good roundness was first synthesized successfully,and the AM parameters for Mg-based alloys were optimized.Based on the optimized parameters,porous JDBM scaffolds with three different architectures(biomimetic,diamond,and gyroid)were then fabricated by selective laser melting(SLM),and their mechanical properties and degradation behavior were evaluated.Finally,the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate(DCPD)coating treatment,which greatly suppressed the degradation rate and increased the cytocompatibility,indicating a promising prospect for clinical application as bone tissue engineering scaffolds.
基金supported by the National Megaprojects for Infectious Diseases (2014ZX10004002-004001)
文摘Three-dimensional(3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover,these models bridge the gap between traditional two-dimensional(2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition,3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models.
文摘The biodegradability and biocompatibility of porous Mg-2Zn(mass fraction, %) scaffolds coated with nano hydroxyapatite(HAP) were investigated. The nano HAP coating on Mg-2Zn scaffolds was prepared by the pulse electrodeposition method. The as-deposited scaffolds were then post-treated with alkaline solution to improve the biodegradation behavior and biocompatibility for implant applications. The microstructure and composition of scaffold and nano HAP coating, as well as their degradation and cytotoxicity behavior in simulated body fluid(SBF) were investigated. The post-treated coating is composed of needle-like HAP with the diameter less than 100 nm developed almost perpendicularly to the substrate, which exhibits a similar composition to natural bone. It is found that the products of immersion in SBF are identified to be HAP,(Ca,Mg)3(PO4)2 and Mg(OH)2. The bioactivity, biocompatibility and cell viabilities for the as-coated and post-treated scaffold extracts are higher than those for the uncoated scaffold. MG63 cells are found to adhere and proliferate on the surface of the as-coated and post-treated scaffolds, making it a promising choice for medical application. The results show that the pulse electrodeposition of nano HAP coating and alkaline treatment is a useful approach to improve the biodegradability and bioactivity of porous Mg-Zn scaffolds.
文摘Porous calcium phosphate ceramics were produced by compression molding using a special mold followed by sintering. The porous calcium phosphate ceramics have three-dimensional and penetrated open pores 380-400μm in diacneter spaced at intervals of 200μm. The layers of the linear penetration pores alternately lay perpendicular to pore direction. The porosity was 59%-65% . The Ca/ P molar ratios of the porous calcium phos phate ceramics range from 1.5 to 1.85. A binder cantaining methyl cellulose was most effective for preparing the powder compact among vinyl acetate, polyvinyl alcohol, starch, stearic acid, methyl cellulose and their mixtures . Stainless steel, polystyrene, nylon and bamboo were used as the long columnar dies for the penetrated open pores. When polystyrene, nylon and bamboo were used as the long columnar male dies, the dies were burned oat during the sintering process. Using stainless steel as the male dies with the removal of the dies before heat treatment resulted in a higher level of densification of the calcium phosphate ceramic.
文摘The authors regret that the given names and family names of all authors in original article were inadvertently switched.The correct order of the given and family names is provided in this document.Rodriguez-Jimenez Francisco Javier,Artero-Castro Ana,Studenovska Hana,Selles Francisca,Arteaga Claramunt Alba Maria,Brymova Anna,Jendelova Pavla,Motlik Jan,Petrovski Goran,Lytvynchuk Lyubomyr,Ardan Taras,TichotováLucie,DrutovičSaskia,Sharma Ruchi,Lukovic Dunja,Bharti Kapil,Erceg Slaven.The authors apologize for any inconvenience this may have caused.
文摘The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have been performed to design and develop suitable scaffolds for spinal cord regeneration, keeping in mind that the reconstruction of a pro-regenerative environment is the key challenge for an effective neurogenesis. The aim of this review is to outline the main features of an ideal scaffold, based on biomaterials, produced by the electrospinning technique and intended for the spinal cord regeneration. An overview of the poly- mers more investigated in the production of neural fibrous scaffolds is also provided.
文摘Three-dimensional porous poly-lactic acid(PLA) scaffold was fabricated using fused deposition modeling(FDM) method including 30%, 50% and 70% nominal porosity. Study of phases in initial polymeric material and printed scaffolds was done by X-ray diffraction(XRD), and no significant phase difference was observed due to the manufacturing process, and the poly-lactic acid retains its crystalline properties. The results of the mechanical properties evaluation by the compression test show that the mechanical properties of the scaffold have decreased significantly with increasing the porosity of scaffold. The microstructure of scaffolds were studied by scanning electron microscope(SEM), showing that the pores had a regular arrangement and their morphology changed with porosity change. The mechanical properties of the poly-lactic acid scaffolds printed using fused deposition modeling, can be adapted to the surrounding tissue, by porosity change.
基金China Scholarship Council (CSC) for financial support。
文摘Porous biodegradable Mg and its alloys are considered to have a great potential to serve as ideal bone substitutes.The recent progress in additive manufacturing(AM) has prompted its application to fabricate Mg scaffolds with geometrically ordered porous structures.Extrusionbased AM,followed by debinding and sintering,has been recently demonstrated as a powerful approach to fabricating such Mg scaffolds,which can avoid some crucial problems encountered when applying powder bed fusion AM techniques.However,such pure Mg scaffolds exhibit a too high rate of in vitro biodegradation.In the present research,alloying through a pre-alloyed Mg-Zn powder was ultilized to enhance the corrosion resistance and mechanical properties of AM geometrically ordered Mg-Zn scaffolds simultaneously.The in vitro biodegradation behavior,mechanical properties,and electrochemical response of the fabricated Mg-Zn scaffolds were evaluated.Moreover,the response of preosteoblasts to these scaffolds was systematically evaluated and compared with their response to pure Mg scaffolds.The Mg-Zn scaffolds with a porosity of 50.3% and strut density of 93.1% were composed of the Mg matrix and MgZn2second phase particles.The in vitro biodegradation rate of the Mg-Zn scaffolds decreased by 81% at day 1,as compared to pure Mg scaffolds.Over 28 days of static immersion in modified simulated body fluid,the corrosion rate of the Mg-Zn scaffolds decreased from 2.3± 0.9 mm/y to 0.7±0.1 mm/y.The yield strength and Young’s modulus of the Mg-Zn scaffolds were about 3 times as high as those of pure Mg scaffolds and remained within the range of those of trabecular bone throughout the biodegradation tests.Indirect culture of MC3T3-E1 preosteoblasts in Mg-Zn extracts indicated favorable cytocompatibility.In direct cell culture,some cells could spread and form filopodia on the surface of the Mg-Zn scaffolds.Overall,this study demonstrates the great potential of the extrusion-based AM Mg-Zn scaffolds to be further developed as biodegradable bone-substituting biomaterials.
基金the sub project of the national major project generation method and application verification of personalized rehabilitation prescription for patients with balance(No.2019YFB1311403)。
文摘The biodegradable substitution materials for bone tissue engineering have been a research hotspot.As is known to all,the biodegradability,biocompatibility,mechanical properties and plasticity of the substitution materials are the important indicators for the application of implantation materials.In this article,we reported a novel binary substitution material by blending the poly(lactic-acid)-co-(trimethylenecarbonate)and poly(glycolic-acid)-co-(trimethylene-carbonate),which are both biodegradable polymers with the same segment of flexible trimethylene-carbonate in order to accelerate the degradation rate of poly(lactic-acid)-co-(trimethylene carbonate)substrate and improve its mechanical properties.Besides,we further fabricate the porous poly(lactic-acid)-co-(trimethylene-carbonate)/poly(glycolic-acid)-co-(trimethylene-carbonate)scaffolds with uniform microstructure by the 3D extrusion printing technology in a mild printing condition.The physicochemical properties of the poly(lactic-acid)-co-(trimethylenecarbonate)/poly(glycolic-acid)-co-(trimethylene-carbonate)and the 3D printing scaffolds were investigated by universal tensile dynamometer,fourier transform infrared reflection(FTIR),scanning electron microscope(SEM)and differential scanning calorimeter(DSC).Meanwhile,the degradability of the PLLATMC/GA-TMC was performed in vitro degradation assays.Compared with PLLA-TMC group,PLLA-TMC/GATMC groups maintained the decreasing Tg,higher degradation rate and initial mechanical performance.Furthermore,the PLLA-TMC/GA-TMC 3D printing scaffolds provided shape-memory ability at 37℃.In summary,the PLLA-TMC/GA-TMC can be regarded as an alternative substitution material for bone tissue engineering.
基金the National "863" Project of China(2003AA205181)
文摘A new method of fabricating porous polymer scaffolds was developed, using sodium hydrogen carbonate particulates as the porogen to foam. The pore structure of polymer scaffolds can easily be manipulated by controlling the size and weight fraction of sodium hydrogen carbonate particulates. The scaffolds are highly porous with a porosity greater than 90% and with a larger pore size ranging from 100-400μm, and are well distributed with the interconnected and open pore wall structure which is necessary for tissue engineering. We investigated the effect of the porosity of scaffolds, the pore size of scaffolds and material of polymer on the mechanical properties of scaffolds. The scaffolds fabricated by the method have more big pores than those by the convenient method of salt leaching.
文摘Objective To investigate the possibility to fabricate a blood vessel scaffold with a combined polymer for tissue engineering. Methods A blood vessel scaffold was designed with a combined polymer composed of rabbit vascular smooth muscle cells ( VSMCs), collagen and a non-spinning fabric mesh of polyglycolic acid(PGA). VSMQ were implanted into collagen gel and their growth was observed. The mixed solution of VSMQ and collagen was dropped into the tubular scaffold, followed by 7-day culturing. Results VSMQ formed many prominences after culturing in gelatinous collagen for 3 - 4 hours. With cells extending, some cells became shuttle-or spindle-shaped. After VSMQ-collagen complex was implanted into the PGA mesh, most of VSMCs remained in the pore of PGA mesh with the formation of gelation. VSMCs could adhere to and grow on the PGA fiber. Conclusion The non-spinning PGA porous biodegradable material coated with collagen is a good carrier for VSMCs to adhere and grow. 5 refs,3 figs.