Polycaprolactone(PCL)scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field.Due to the intrinsic limitations of PCL,carbon nanomateria...Polycaprolactone(PCL)scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field.Due to the intrinsic limitations of PCL,carbon nanomaterials are often investigated to reinforce the PCL scaffolds.Despite several studies that have been conducted on carbon nanomaterials,such as graphene(G)and graphene oxide(GO),certain challenges remain in terms of the precise design of the biological and nonbiological properties of the scaffolds.This paper addresses this limitation by investigating both the nonbiological(element composition,surface,degradation,and thermal and mechanical properties)and biological characteristics of carbon nanomaterial-reinforced PCL scaffolds for bone tissue engineering applications.Results showed that the incorporation of G and GO increased surface properties(reduced modulus and wettability),material crystallinity,crystallization temperature,and degradation rate.However,the variations in compressive modulus,strength,surface hardness,and cell metabolic activity strongly depended on the type of reinforcement.Finally,a series of phenomenological models were developed based on experimental results to describe the variations of scaffold’s weight,fiber diameter,porosity,and mechanical properties as functions of degradation time and carbon nanomaterial concentrations.The results presented in this paper enable the design of three-dimensional(3D)bone scaffolds with tuned properties by adjusting the type and concentration of different functional fillers.展开更多
A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-( PEG-Asp )n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- ( PEG-Asp )n cop...A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-( PEG-Asp )n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- ( PEG-Asp )n copolymer with pendant amine functional groups and enhanced hydrophilicity woo synthesized by bulk ring-opening copolymerization by DL-lactide( DLLA) and glycolide( GA ) with Aspartic acid ( Asp )-Polyethylene glycol(PEG) alt-prepolymer. A Three-dimensional, porous scaffold of the PLGA-( PEG- Asp)n copolymer was fabricated by a solvent casting , particulate leaching process. The scaffold woo then incubated in modified simulated body fluid (naSBF). Growth of HA nanocrystals on the inner pore surfaces of the porous scaffold is confirmed by calcium ion binding analyses, SEM , mass increooe meoourements and quantification of phosphate content within scaffolds. SEM analysis demonstrated the nucleation and growth of a continuous bonelike, low crystalline carbonated HA nanocrystals on the inner pore surfaces of the PLGA- ( PEG-Asp )n scaffolds. The amount of calcium binding, total mass and the mass of phosphate on experimental PLGA- ( PEG-Asp ) n scaffolds at different incubation times in mSBF was significantly greater than that of control PLGA scaffolds. This nano-HA/ PLGA-( PEG- Asp )n composite stunts some features of natural bone both in main composition and hierarchical microstrueture. The Asp- PEG alt-prepolymer modified PleA copolymer provide a controllable high surface density and distribution of anionic functional groups which would enhance nucleation and growth of bonelike mineral following exposure to mSBF. This biomimetic treatment provides a simple method for surface functionalization and sabsequent mineral nucleation and self-oosembling on bodegradable polymer scaffolds for tissue engineering.展开更多
Bone damage caused by trauma and tumors is a serious problem for human health, therefore, three-dimensional (3D) scaffolding materials that stimulate and promote the regeneration of broken bone tissues have become the...Bone damage caused by trauma and tumors is a serious problem for human health, therefore, three-dimensional (3D) scaffolding materials that stimulate and promote the regeneration of broken bone tissues have become the focus of current research in the field of bone damage repair.To this regard, a preferential combination of materials and preparation techniques is considered crucial for the preparation of advanced bone tissue engineering scaffolds to better facilitate the regeneration of broken bone.In this review, current research advances and challenges in bone tissue engineering scaffolds are discussed and analyzed in detail.First, we elucidated the structure and self-healing mechanism of bone tissue.Subsequently, the main applications of different materials, including inorganic and organic materials, in bone tissue engineering scaffolds are summarized.Moreover, we overview the latest research progress of the mainstream preparation strategies of bone tissue engineering scaffolds, and provide an in-depth analysis of the different advantages of each method.Finally, promising future directions and challenges of bone tissue engineering scaffolds are systematically discussed.展开更多
Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnec...Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems.In this work,biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting.Mg scaffold with better interconnectivity showed lower mechanical strength.Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration,pH value and osmolality of the degradation microenvironment due to the lower specific surface area.Nevertheless,the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit.Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size.In summary,design of interconnectivity in terms of pore size distribution could regulate mechanical strength,microenvironment in cell culture condition and cell migration potential,and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.展开更多
Colloidal gels made of oppositely charged nanoparticles are a novel class of hydrogels and can exhibit pseudoplastic behavior which will enable them to mold easily into specific shapes.These moldable gels can be used ...Colloidal gels made of oppositely charged nanoparticles are a novel class of hydrogels and can exhibit pseudoplastic behavior which will enable them to mold easily into specific shapes.These moldable gels can be used as building blocks to self-assemble into integral scaffolds from bottom to up through electrostatic forces.However,they are too weak to maintain scaffold morphology just depending on interparticle interactions such as Van der Waals attraction and electrostatic forces especially for bone tissue engineering.In this study,oppositely charged gelatin nanoparticles were firstly prepared by two-step desolvation method,followed by the mixture with water to form colloid gels.To solve the problem of weak mechanical performance of colloid gels, gelatin macromolecules were introduced into the prepared gels to form blend gels.The blend gels can be easily processed into three-dimensional( 3D) porous scaffolds via motor assisted microsyringe( MAM)system,a nozzle-based rapid prototyping technology,under mild conditions.After fabrication the scaffolds were crosslinked by glutaraldehyde( GA,25% solution in water by weight),then the crosslinked gelatin macromolecules network could form to improve the mechanical properties of colloid gels.The average particle size and zeta potential of gelatin nanoparticles were measured by NanoZS instrument.The morphology and microstructures of scaffolds were characterized by macroscopic images.The mechanical properties of the scaffolds were studied by a universal material testing machine.展开更多
A novel method of designing and preparing bone tissue engineering scaffolds with controllable porous structure of both macro channels and micro pores was proposed. The CAD software UG NX3.0 was used to design the macr...A novel method of designing and preparing bone tissue engineering scaffolds with controllable porous structure of both macro channels and micro pores was proposed. The CAD software UG NX3.0 was used to design the macro channels' shape, size and distribution. By integrating rapid prototyping and traditional porogen technique, the macro channels and micro pores were formed respectively. The size, shape and quantity of micro pores were controlled by porogen particulates. The sintered β-TCP porous scaffolds possessed connective macro channels of approximately 500 μm and micro pores of 200-400 μm. The porosity and connectivity of micro pores became higher with the increase of porogen ratio, while the mechanical properties weakened. The average porosity and compressive strength offl-TCP scaffolds prepared with porogen ratio of 60wt% were 78.12% and 0.2983 MPa, respectively. The cells' adhesion ratio of scaffolds was 67.43%. The ALP activity, OCN content and cells micro morphology indicated that cells grew and proliferated well on the scaffolds.展开更多
The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/...The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.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
AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional ...AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties.展开更多
The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical te...The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental "origin" require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.展开更多
Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians.Current failures of autografts and allografts in many pathological conditions have prompted researchers to f...Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians.Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility,biodegradability and osteoinductivity.Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells(MSCs).In particular,a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue.These adipose stem cells(ASCs)can be obtained in large quantities with little donor site morbidity or patient discomfort,in contrast to the invasive and painful isolation of bone marrow MSCs.The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models,with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients.Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration,the lack of standardization in applied techniques makes the comparison between studies difficult.Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns,which must be resolved to permit application in regenerative medicine.展开更多
Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair material.Unfortunately,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologi...Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair material.Unfortunately,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologic reactions,infection risks,and geometrical mismatching concerns hampered tissue graft use and underscored the need for scaffolds for more effective bone reconstructions due to their tunable properties.Significant progress has been carried out in past decade in the fields of nanoceramics synthesis,bioconjugate chemistry,and composite material processing.This review outlines hierarchical structures and biology of bone tissue,materialistic compo-nents of scaffolds(bioceramics,polymers,bioactive drugs),featured scaffolding strategies(nanofibers,hydrogels,aerogels,bioprinting,and fiber-reinforced composite),and emphasis that hierarchical and physiochemical char-acteristics of bone should be used as an inspiration for scaffold design.This review discussed how differences in materiobiological aspects of scaffolds,such as polymer/bioceramic nanocomposite,mineralized nanocomposite,matrix-rich nanocomposite,3D microenvironmental cues,pore space cues,mechanical cues,usage of physical stimulation(magnetic,electroactive,and photoactivated cues),surface cues(wettability,roughness,textured,and surface charge),and biointerface cues(cell-biomaterial interactions,cell-selective homing,and cell regula-tory strategies)modulate cellular and biological response for bone tissue engineering.This study further outlines the challenges and benefits of integrating materiobiological cues of scaffolds for bone tissue engineering.展开更多
Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. ...Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.展开更多
In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite materials.In this study,c...In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite materials.In this study,carbon nanotubes/polylactic acid/hydroxyapatite(CNTs/PLA/HA)scaffolds with different contents(0.5,1,1.5 and 2 wt.%)of CNTs were prepared by the thermally induced phase separation(TIPS)method.The results revealed that the composite scaffolds had uniform pores with high porosities over 68%and high through performances.The addition of CNTs significantly enhanced the mechanical properties of resulted PLA/HA,in which the 1.5 wt.%CNTs/PLA/HA composite scaffold demonstrated the optimum mechanical behaviors with the bending elastic modulus of(868.5±12.34)MPa,the tensile elastic modulus of(209.51±12.73)MPa,and the tensile strength of(3.26±0.61)MPa.Furthermore,L929 cells on the 1.5 wt.%CNTs/PLA/HA scaffold displayed good spreading performance and favorable cytocompatibility.Therefore,it is expected that the 1.5 wt.%CNTs/PLA/HA scaffold has potential applications in bone tissue engineering.展开更多
Bone-tissue defects affect millions of people worldwide.Despite being common treatment approaches,autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect.This has prompted researchers to...Bone-tissue defects affect millions of people worldwide.Despite being common treatment approaches,autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect.This has prompted researchers to explore novel bone-regeneration methods.In recent decades,the development of bone tissue engineering(BTE)scaffolds has been leading the forefront of this field.As researchers have provided deep insights into bone physiology and the bone-healing mechanism,various biomimicking and bioinspired BTE scaffolds have been reported.Now it is necessary to review the progress of natural bone physiology and bone healing mechanism,which will provide more valuable enlightenments for researchers in this field.This work details the physiological microenvironment of the natural bone tissue,bone-healing process,and various biomolecules involved therein.Next,according to the bone physiological microenvironment and the delivery of bioactive factors based on the bone-healing mechanism,it elaborates the biomimetic design of a scaffold,highlighting the designing of BTE scaffolds according to bone biology and providing the rationale for designing next-generation BTE scaffolds that conform to natural bone healing and regeneration.展开更多
3D printing technology is an emerging technology.It constructs solid bodies by stacking materials layer by layer,and can quickly and accurately prepare bone tissue engineering scaffolds with specific shapes and struct...3D printing technology is an emerging technology.It constructs solid bodies by stacking materials layer by layer,and can quickly and accurately prepare bone tissue engineering scaffolds with specific shapes and structures to meet the needs of different patients.The field of life sciences has received a great deal of attention.However,different 3D printing technologies and materials have their advantages and disadvantages,and there are limitations in clinical application.In this paper,the technology,materials and clinical applications of 3D printed bone tissue engineering scaffolds are reviewed,and the future development trends and challenges in this field are prospected.展开更多
In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we dev...In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.展开更多
BACKGROUND: The potential application of decellularized liver scaffold for liver regeneration is limited by severe shortage of donor organs. Attempt of using heterograft scaffold is accompanied with high risks of zoo...BACKGROUND: The potential application of decellularized liver scaffold for liver regeneration is limited by severe shortage of donor organs. Attempt of using heterograft scaffold is accompanied with high risks of zoonosis and immunological rejection. We proposed that the spleen, which procured more extensively than the liver, could be an ideal source of decellularized scaffold for liver regeneration. METHODS: After harvested from donor rat, the spleen was processed by 12-hour freezing/thawing ×2 cycles, then circulation perfusion of 0.02% trypsin and 3% Triton X-100 sequentially through the splenic artery for 32 hours in total to prepare decellularized scaffold. The structure and component characteristics of the scaffold were determined by hematoxylin and eosin and immumohistochemical staining, scanning electron microscope, DNA detection, porosity measurement, biocompatibility and cytocompatibility test. Recellularization of scaffold by 5×106 bone marrow mesenchymal stem cells(BMSCs) was carried out to preliminarily evaluate the feasibility of liver regeneration by BMSCs reseeding and differentiation in decellularized splenic scaffold.RESULTS: After decellularization, a translucent scaffold, which retained the gross shape of the spleen, was generated. Histological evaluation and residual DNA quantitation revealed the remaining of extracellular matrix without nucleus and cytoplasm residue. Immunohistochemical study proved the existence of collagens I, IV, fibronectin, laminin and elastin in decellularized splenic scaffold, which showed a similarity with decellularized liver. A scanning electron microscope presented the remaining three-dimensional porous structure of extracellular matrix and small blood vessels. The poros-ity of scaffold, aperture of 45.36±4.87 μm and pore rate of 80.14%±2.99% was suitable for cell engraftment. Subcutaneous implantation of decellularized scaffold presented good histocompatibility, and recellularization of the splenic scaffold demonstrated that BMSCs could locate and survive in the decellularized matrix. CONCLUSION: Considering the more extensive organ source and satisfying biocompatibility, the present study indicated that the three-dimensional decellularized splenic scaffold might have considerable potential for liver regeneration when combined with BMSCs reseeding and differentiation.展开更多
Bone defects caused by trauma,tumor,congenital abnormality and osteoarthritis,etc.have been substantially impacted the lives and health of human.Artificial bone implants,like bioceramic-based scaffolds,provide signifi...Bone defects caused by trauma,tumor,congenital abnormality and osteoarthritis,etc.have been substantially impacted the lives and health of human.Artificial bone implants,like bioceramic-based scaffolds,provide significant benefits over biological counterparts and are critical for bone repair and regeneration.However,it is highly probable that bacterial infections occur in the surgical procedures or on bioceramic-based scaffolds.Therefore,it is of great significance to obtain bioceramic-based scaffolds with integrative antibacterial and osteogenic functions for treating bone implant-associated infection and promoting bone repair.To fight against infection problems,bioceramic-based scaffolds with various antibacterial strategies are developed for bone repair and regeneration and also have made great progresses.This review summarizes recent progresses in bioceramic-based scaffolds with antibacterial function,which include drug-induced,ion-mediated,physical-activated and their combined antibacterial strategies according to specific antibacterial mechanism.Finally,the challenges and opportunities of antibacterial bioceramic-based scaffolds are discussed.展开更多
基金The authors wish to acknowledge Engineering and Physical Sciences Research Council(EPSRC)UK for the Global Challenges Research Fund(No.EP/R015139/1)Rosetrees Trust UK&Stoneygate Trust UK for the Enterprise Fellowship(Ref:M874).
文摘Polycaprolactone(PCL)scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field.Due to the intrinsic limitations of PCL,carbon nanomaterials are often investigated to reinforce the PCL scaffolds.Despite several studies that have been conducted on carbon nanomaterials,such as graphene(G)and graphene oxide(GO),certain challenges remain in terms of the precise design of the biological and nonbiological properties of the scaffolds.This paper addresses this limitation by investigating both the nonbiological(element composition,surface,degradation,and thermal and mechanical properties)and biological characteristics of carbon nanomaterial-reinforced PCL scaffolds for bone tissue engineering applications.Results showed that the incorporation of G and GO increased surface properties(reduced modulus and wettability),material crystallinity,crystallization temperature,and degradation rate.However,the variations in compressive modulus,strength,surface hardness,and cell metabolic activity strongly depended on the type of reinforcement.Finally,a series of phenomenological models were developed based on experimental results to describe the variations of scaffold’s weight,fiber diameter,porosity,and mechanical properties as functions of degradation time and carbon nanomaterial concentrations.The results presented in this paper enable the design of three-dimensional(3D)bone scaffolds with tuned properties by adjusting the type and concentration of different functional fillers.
文摘A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-( PEG-Asp )n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- ( PEG-Asp )n copolymer with pendant amine functional groups and enhanced hydrophilicity woo synthesized by bulk ring-opening copolymerization by DL-lactide( DLLA) and glycolide( GA ) with Aspartic acid ( Asp )-Polyethylene glycol(PEG) alt-prepolymer. A Three-dimensional, porous scaffold of the PLGA-( PEG- Asp)n copolymer was fabricated by a solvent casting , particulate leaching process. The scaffold woo then incubated in modified simulated body fluid (naSBF). Growth of HA nanocrystals on the inner pore surfaces of the porous scaffold is confirmed by calcium ion binding analyses, SEM , mass increooe meoourements and quantification of phosphate content within scaffolds. SEM analysis demonstrated the nucleation and growth of a continuous bonelike, low crystalline carbonated HA nanocrystals on the inner pore surfaces of the PLGA- ( PEG-Asp )n scaffolds. The amount of calcium binding, total mass and the mass of phosphate on experimental PLGA- ( PEG-Asp ) n scaffolds at different incubation times in mSBF was significantly greater than that of control PLGA scaffolds. This nano-HA/ PLGA-( PEG- Asp )n composite stunts some features of natural bone both in main composition and hierarchical microstrueture. The Asp- PEG alt-prepolymer modified PleA copolymer provide a controllable high surface density and distribution of anionic functional groups which would enhance nucleation and growth of bonelike mineral following exposure to mSBF. This biomimetic treatment provides a simple method for surface functionalization and sabsequent mineral nucleation and self-oosembling on bodegradable polymer scaffolds for tissue engineering.
基金financially supported by the Fundamental Research Funds for the Central Universities of China(Nos.DUT22QN203 and DUT22YG201).
文摘Bone damage caused by trauma and tumors is a serious problem for human health, therefore, three-dimensional (3D) scaffolding materials that stimulate and promote the regeneration of broken bone tissues have become the focus of current research in the field of bone damage repair.To this regard, a preferential combination of materials and preparation techniques is considered crucial for the preparation of advanced bone tissue engineering scaffolds to better facilitate the regeneration of broken bone.In this review, current research advances and challenges in bone tissue engineering scaffolds are discussed and analyzed in detail.First, we elucidated the structure and self-healing mechanism of bone tissue.Subsequently, the main applications of different materials, including inorganic and organic materials, in bone tissue engineering scaffolds are summarized.Moreover, we overview the latest research progress of the mainstream preparation strategies of bone tissue engineering scaffolds, and provide an in-depth analysis of the different advantages of each method.Finally, promising future directions and challenges of bone tissue engineering scaffolds are systematically discussed.
基金supported by grants from Shenzhen Key Medical Subject(No.SZXK023)Shenzhen“SanMing”Project of Medicine(No.SZSM201612092)+3 种基金Shenzhen Research and Development Projects(No.JCYJ20170307111755218)Guangdong Basic and Applied Basic Research Foundation(No.2019A1515011290)National Key Research and Development Program of China(No.2016YFC1102103)China Postdoctoral Science Foundation(No.2020M672756)
文摘Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems.In this work,biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting.Mg scaffold with better interconnectivity showed lower mechanical strength.Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration,pH value and osmolality of the degradation microenvironment due to the lower specific surface area.Nevertheless,the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit.Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size.In summary,design of interconnectivity in terms of pore size distribution could regulate mechanical strength,microenvironment in cell culture condition and cell migration potential,and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.
基金National Natural Science Foundations of China(Nos.30973105,31271035)Science and Technology Commission of Shanghai Municipality,China(No.11nm0506200)Ph.D.Programs Foundation of Ministry of Education of China(No.20130075110005)
文摘Colloidal gels made of oppositely charged nanoparticles are a novel class of hydrogels and can exhibit pseudoplastic behavior which will enable them to mold easily into specific shapes.These moldable gels can be used as building blocks to self-assemble into integral scaffolds from bottom to up through electrostatic forces.However,they are too weak to maintain scaffold morphology just depending on interparticle interactions such as Van der Waals attraction and electrostatic forces especially for bone tissue engineering.In this study,oppositely charged gelatin nanoparticles were firstly prepared by two-step desolvation method,followed by the mixture with water to form colloid gels.To solve the problem of weak mechanical performance of colloid gels, gelatin macromolecules were introduced into the prepared gels to form blend gels.The blend gels can be easily processed into three-dimensional( 3D) porous scaffolds via motor assisted microsyringe( MAM)system,a nozzle-based rapid prototyping technology,under mild conditions.After fabrication the scaffolds were crosslinked by glutaraldehyde( GA,25% solution in water by weight),then the crosslinked gelatin macromolecules network could form to improve the mechanical properties of colloid gels.The average particle size and zeta potential of gelatin nanoparticles were measured by NanoZS instrument.The morphology and microstructures of scaffolds were characterized by macroscopic images.The mechanical properties of the scaffolds were studied by a universal material testing machine.
基金Funded by the Postdoctor Science Fund of China (No. 20070410715) Shanghai Excellent Youth Special Fund (No. 17014)
文摘A novel method of designing and preparing bone tissue engineering scaffolds with controllable porous structure of both macro channels and micro pores was proposed. The CAD software UG NX3.0 was used to design the macro channels' shape, size and distribution. By integrating rapid prototyping and traditional porogen technique, the macro channels and micro pores were formed respectively. The size, shape and quantity of micro pores were controlled by porogen particulates. The sintered β-TCP porous scaffolds possessed connective macro channels of approximately 500 μm and micro pores of 200-400 μm. The porosity and connectivity of micro pores became higher with the increase of porogen ratio, while the mechanical properties weakened. The average porosity and compressive strength offl-TCP scaffolds prepared with porogen ratio of 60wt% were 78.12% and 0.2983 MPa, respectively. The cells' adhesion ratio of scaffolds was 67.43%. The ALP activity, OCN content and cells micro morphology indicated that cells grew and proliferated well on the scaffolds.
基金National Natural Science Foundations of China(Nos.31271028,31570984)Innovation Program of Shanghai Municipal Education Commission,China(No.13ZZ051)+2 种基金International Cooperation Fund of the Science and Technology Commission of Shanghai Municipality,China(No.15540723400)Open Foundation of State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,China(No.LK1416)“111 Project” Biomedical Textile Materials Science and Technology,China(No.B07024)
文摘The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.
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.
文摘AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties.
文摘The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental "origin" require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.
基金Supported by The Regione Toscana-POR CRO FSE 2007-2013 and I.F.B.STRODER s.r.l
文摘Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians.Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility,biodegradability and osteoinductivity.Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells(MSCs).In particular,a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue.These adipose stem cells(ASCs)can be obtained in large quantities with little donor site morbidity or patient discomfort,in contrast to the invasive and painful isolation of bone marrow MSCs.The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models,with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients.Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration,the lack of standardization in applied techniques makes the comparison between studies difficult.Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns,which must be resolved to permit application in regenerative medicine.
基金supported by National Natural Science Foundation of China (31971326)Science and Technology Project of Suzhou (ZXT2022007).
文摘Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair material.Unfortunately,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologic reactions,infection risks,and geometrical mismatching concerns hampered tissue graft use and underscored the need for scaffolds for more effective bone reconstructions due to their tunable properties.Significant progress has been carried out in past decade in the fields of nanoceramics synthesis,bioconjugate chemistry,and composite material processing.This review outlines hierarchical structures and biology of bone tissue,materialistic compo-nents of scaffolds(bioceramics,polymers,bioactive drugs),featured scaffolding strategies(nanofibers,hydrogels,aerogels,bioprinting,and fiber-reinforced composite),and emphasis that hierarchical and physiochemical char-acteristics of bone should be used as an inspiration for scaffold design.This review discussed how differences in materiobiological aspects of scaffolds,such as polymer/bioceramic nanocomposite,mineralized nanocomposite,matrix-rich nanocomposite,3D microenvironmental cues,pore space cues,mechanical cues,usage of physical stimulation(magnetic,electroactive,and photoactivated cues),surface cues(wettability,roughness,textured,and surface charge),and biointerface cues(cell-biomaterial interactions,cell-selective homing,and cell regula-tory strategies)modulate cellular and biological response for bone tissue engineering.This study further outlines the challenges and benefits of integrating materiobiological cues of scaffolds for bone tissue engineering.
基金supported by the Sichuan Science and Technology Program,No.2023YFS0164 (to JC)。
文摘Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.
基金supported by the National Natural Science Foundation of China(Grant Nos.12202302,12272253,and 82103147)The support of the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province(Grant No.20220006)was also acknowledged with gratitude.
文摘In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite materials.In this study,carbon nanotubes/polylactic acid/hydroxyapatite(CNTs/PLA/HA)scaffolds with different contents(0.5,1,1.5 and 2 wt.%)of CNTs were prepared by the thermally induced phase separation(TIPS)method.The results revealed that the composite scaffolds had uniform pores with high porosities over 68%and high through performances.The addition of CNTs significantly enhanced the mechanical properties of resulted PLA/HA,in which the 1.5 wt.%CNTs/PLA/HA composite scaffold demonstrated the optimum mechanical behaviors with the bending elastic modulus of(868.5±12.34)MPa,the tensile elastic modulus of(209.51±12.73)MPa,and the tensile strength of(3.26±0.61)MPa.Furthermore,L929 cells on the 1.5 wt.%CNTs/PLA/HA scaffold displayed good spreading performance and favorable cytocompatibility.Therefore,it is expected that the 1.5 wt.%CNTs/PLA/HA scaffold has potential applications in bone tissue engineering.
基金National Natural Science Foundation of China(81771048,81870743)Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202012)Sichuan Science and Technology Program(2020YFS0170).
文摘Bone-tissue defects affect millions of people worldwide.Despite being common treatment approaches,autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect.This has prompted researchers to explore novel bone-regeneration methods.In recent decades,the development of bone tissue engineering(BTE)scaffolds has been leading the forefront of this field.As researchers have provided deep insights into bone physiology and the bone-healing mechanism,various biomimicking and bioinspired BTE scaffolds have been reported.Now it is necessary to review the progress of natural bone physiology and bone healing mechanism,which will provide more valuable enlightenments for researchers in this field.This work details the physiological microenvironment of the natural bone tissue,bone-healing process,and various biomolecules involved therein.Next,according to the bone physiological microenvironment and the delivery of bioactive factors based on the bone-healing mechanism,it elaborates the biomimetic design of a scaffold,highlighting the designing of BTE scaffolds according to bone biology and providing the rationale for designing next-generation BTE scaffolds that conform to natural bone healing and regeneration.
基金funded by Versus Arthritis UK(Grant No.21977)European Commission via a H2020-MSCA-RISE programme(BAMOS,Grant No.734156)+1 种基金Innovative UK via Newton Fund(Grant No.102872)Engineering and Physical Science Research Council(EPSRC)via DTP CASE programme(Grant No.EP/T517793/1).
文摘3D printing technology is an emerging technology.It constructs solid bodies by stacking materials layer by layer,and can quickly and accurately prepare bone tissue engineering scaffolds with specific shapes and structures to meet the needs of different patients.The field of life sciences has received a great deal of attention.However,different 3D printing technologies and materials have their advantages and disadvantages,and there are limitations in clinical application.In this paper,the technology,materials and clinical applications of 3D printed bone tissue engineering scaffolds are reviewed,and the future development trends and challenges in this field are prospected.
基金supported by the National Key R&D Program of China[grant number 2021YFC2400700]the National Natural Science Foundation of China[grant numbers 82170929,81970908 and 81771039].
文摘In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.
基金supported by a grant from the Specialized Research Fund for the Doctoral Program of Higher Education of China(20110201130009)
文摘BACKGROUND: The potential application of decellularized liver scaffold for liver regeneration is limited by severe shortage of donor organs. Attempt of using heterograft scaffold is accompanied with high risks of zoonosis and immunological rejection. We proposed that the spleen, which procured more extensively than the liver, could be an ideal source of decellularized scaffold for liver regeneration. METHODS: After harvested from donor rat, the spleen was processed by 12-hour freezing/thawing ×2 cycles, then circulation perfusion of 0.02% trypsin and 3% Triton X-100 sequentially through the splenic artery for 32 hours in total to prepare decellularized scaffold. The structure and component characteristics of the scaffold were determined by hematoxylin and eosin and immumohistochemical staining, scanning electron microscope, DNA detection, porosity measurement, biocompatibility and cytocompatibility test. Recellularization of scaffold by 5×106 bone marrow mesenchymal stem cells(BMSCs) was carried out to preliminarily evaluate the feasibility of liver regeneration by BMSCs reseeding and differentiation in decellularized splenic scaffold.RESULTS: After decellularization, a translucent scaffold, which retained the gross shape of the spleen, was generated. Histological evaluation and residual DNA quantitation revealed the remaining of extracellular matrix without nucleus and cytoplasm residue. Immunohistochemical study proved the existence of collagens I, IV, fibronectin, laminin and elastin in decellularized splenic scaffold, which showed a similarity with decellularized liver. A scanning electron microscope presented the remaining three-dimensional porous structure of extracellular matrix and small blood vessels. The poros-ity of scaffold, aperture of 45.36±4.87 μm and pore rate of 80.14%±2.99% was suitable for cell engraftment. Subcutaneous implantation of decellularized scaffold presented good histocompatibility, and recellularization of the splenic scaffold demonstrated that BMSCs could locate and survive in the decellularized matrix. CONCLUSION: Considering the more extensive organ source and satisfying biocompatibility, the present study indicated that the three-dimensional decellularized splenic scaffold might have considerable potential for liver regeneration when combined with BMSCs reseeding and differentiation.
基金the National Natural Science Foundation of China(No.51872185,52072246,32130062)Science and Technology Commission of Shanghai Municipality(No.20442420300)China Postdoctoral Science Foundation(No.2021M703332).
文摘Bone defects caused by trauma,tumor,congenital abnormality and osteoarthritis,etc.have been substantially impacted the lives and health of human.Artificial bone implants,like bioceramic-based scaffolds,provide significant benefits over biological counterparts and are critical for bone repair and regeneration.However,it is highly probable that bacterial infections occur in the surgical procedures or on bioceramic-based scaffolds.Therefore,it is of great significance to obtain bioceramic-based scaffolds with integrative antibacterial and osteogenic functions for treating bone implant-associated infection and promoting bone repair.To fight against infection problems,bioceramic-based scaffolds with various antibacterial strategies are developed for bone repair and regeneration and also have made great progresses.This review summarizes recent progresses in bioceramic-based scaffolds with antibacterial function,which include drug-induced,ion-mediated,physical-activated and their combined antibacterial strategies according to specific antibacterial mechanism.Finally,the challenges and opportunities of antibacterial bioceramic-based scaffolds are discussed.