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1.
Three–dimensional, microperiodic scaffolds of regenerated silk fibroin have been fabricated for tissue engineering by direct ink writing. The ink, which consisted of silk fibroin solution from the Bombyx mori silkworm, was deposited in a layer‐by‐layer fashion through a fine nozzle to produce a 3D array of silk fibers of diameter 5 µm. The extruded fibers crystallized when deposited into a methanol‐rich reservoir, retaining a pore structure necessary for media transport. The rheological properties of the silk fibroin solutions were investigated and the crystallized silk fibers were characterized for structure and mechanical properties by infrared spectroscopy and nanoindentation, respectively. The scaffolds supported human bone marrow‐derived mesenchymal stem cell (hMSC) adhesion, and growth. Cells cultured under chondrogenic conditions on these scaffolds supported enhanced chondrogenic differentiation based on increased glucosaminoglycan production compared to standard pellet culture. Our results suggest that 3D silk fibroin scaffolds may find potential application as tissue engineering constructs due to the precise control of their scaffold architecture and their biocompatibility.  相似文献   

2.
The need for implants to repair large bone defects is driving the development of porous synthetic scaffolds with the requisite mechanical strength and toughness in vivo. Recent developments in the use of design principles and novel fabrication technologies are paving the way to create synthetic scaffolds with promising potential for reconstituting bone in load‐bearing sites. Here, the state of the art in the design and fabrication of bioactive glass and ceramic scaffolds that have improved mechanical properties for structural bone repair is reviewed. Scaffolds with anisotropic and periodic structures can be prepared with compressive strengths comparable to human cortical bone (100?150 MPa), while scaffolds with an isotropic structure typically have strengths in the range of trabecular bone (2?12 MPa). However, the mechanical response of bioactive glass and ceramic scaffolds in multiple loading modes such as flexure and torsion—as well as their mechanical reliability, fracture toughness, and fatigue resistance—has received little attention. Inspired by the designs of natural materials such as cortical bone and nacre, glass‐ceramic and inorganic/polymer composite scaffolds created with extrinsic toughening mechanisms are showing potential for both high strength and mechanical reliability. Future research should include improved designs that provide strong scaffolds with microstructures conducive to bone ingrowth, and evaluation of these scaffolds in large animal models for eventual translation into clinical applications.  相似文献   

3.
Here, ultrathin, flexible, and sustainable nanofiber‐based piezoelectric nanogenerators (NF‐PENGs) are fabricated and applied as wave energy harvesters. The NF‐PENGs are composed of poly(vinylidene fluoride‐co‐trifluoroethylene) (P(VDF‐TrFE)) nanofibers with embedded barium strontium titanate (BaSrTiO3) nanoparticles, which are fabricated by using facile, scalable, and cost‐effective fiber‐forming methods, including electrospinning and solution blowing. The inclusion of ferroelectric BaSrTiO3 nanoparticles inside the electrospun P(VDF‐TrFE) nanofibers enhances the sustainability of the NF‐PENGs and results in unique flexoelectricity‐enhanced piezoelectric nanofibers. Not only do these NF‐PENGs yield a superior performance compared to the previously reported NF‐PENGs, but they also exhibit an outstanding durability in terms of mechanical properties and cyclability. Furthermore, a new theoretical estimate of the energy harvesting efficiency from the water waves is introduced here, which can also be employed in future studies associated with various nanogenerators, including PENGs and triboelectric nanogenerators.  相似文献   

4.
Chemotherapy resistance and bone defects caused by surgical excision of osteosarcoma have been formidable challenges for clinical treatment. Although recently developed nanocatalysts based on Fenton‐like reactions for catalytic therapy demonstrate high potential to eliminate chemotherapeutic‐insensitive tumors, insufficient concentration of intrinsic hydrogen peroxide (H2O2) and low intratumoral penetrability hinder their applications and therapeutic efficiency. The synchronous enriching intratumor H2O2 amount or nanoagents and promoting osteogenesis are intriguing strategies to solve the dilemma in osteosarcoma therapy. Herein, a multifunctional “all‐in‐one” biomaterial platform is constructed by co‐loading calcium peroxide (CaO2) and iron oxide (Fe3O4) nanoparticles into a three‐dimensional (3D) printing akermanite scaffold (AKT‐Fe3O4‐CaO2). The loaded CaO2 nanoparticles act as H2O2 sources to achieve H2O2 self‐sufficient nanocatalytic osteosarcoma therapy as catalyzed by coloaded Fe3O4 nanoagents, as well as provide calcium ion (Ca2+) pools to enhance bone regeneration. The synergistic osteosarcoma‐therapeutic effect is achieved from both magnetic hyperthermia as‐enabled by Fe3O4 nanoparticles under alternative magnetic fields and hyperthermia‐enhanced Fenton‐like nanocatalytic reaction for producing highly toxic hydroxyl radicals. Importantly, the constructed 3D AKT‐Fe3O4‐CaO2 composite scaffolds are featured with favorable bone‐regeneration activity, providing a worthy base and positive enlightenment for future osteosarcoma treatment with bone defects by the multifunctional biomaterial platforms.  相似文献   

5.
Owing to the different biological properties of articular cartilage and subchondral bone, it remains significant challenge to construct a bi‐lineage constructive scaffold. In this study, manganese (Mn)‐doped β‐TCP (Mn‐TCP) scaffolds with varied Mn contents are prepared by a 3D‐printing technology. The effects of Mn on the physicochemical properties, bioactivity, and corresponding mechanism for stimulating osteochondral regeneration are systematically investigated. The incorporation of Mn into β‐TCP lowers the lattices parameters and crystallization temperatures, but improves the scaffold density and compressive strength. The ionic products from Mn‐TCP significantly improve the proliferation of both rabbit chondrocytes and mesenchymal stem cells (rBMSCs), as well as promote the differentiation of chondrocytes and rBMSCs. The in vivo study shows that Mn‐TCP scaffolds distinctly improve the regeneration of subchondral bone and cartilage tissues as compared to TCP scaffolds, upon transplantation in rabbit osteochondral defects for 8 and 12 weeks. The mechanism is closely related to the Mn2+ ions significantly stimulated the proliferation and differentiation of chondrocytes through activating HIF pathway and protected chondrocytes from the inflammatory osteoarthritis environment by activating autophagy. These findings suggest that 3D‐printing of Mn‐containing scaffolds with improved physicochemical properties and bilineage bioactivities represents an intelligent strategy for regenerating osteochondral defects.  相似文献   

6.
Hybrid 2D polymeric–ceramic biosupports are fabricated by mixing a nanostructured CeO2 powder with 85:15 poly(D,L ‐lactic‐co‐glycolic acid) (PLGA)/dichloromethane solutions at specific concentrations, followed by solvent casting onto pre‐patterned molds. The mold patterning allows the orientation of ceramic nanoparticles into parallel lines within the composite scaffold. The ability of the produced films to host and address cell growth is evaluated after 1, 3, and 6 days of culturing with murine derived cardiac and mesenchymal stem cells (CSCs and MSCs), and compared with PLGA films without ceramics and loaded with nanostructured TiO2. Aligned cell growth is observed only for scaffolds that incorporate oriented ceramic nanoparticles, attributed to the nanoceramic ability to modulate the roughness pitch, thus improving cell sensitivity towards the host surface features. Better CSC and MSC proliferative activity is observed for CeO2 composites with respect to either TiO2‐added or unfilled PLGA films. This evidence may be related to the nanostructured CeO2 antioxidative properties.  相似文献   

7.
Patients with diabetes mellitus (DM) suffer from a high risk of fractures and poor bone healing ability. Surprisingly, no effective therapy is available to treat diabetic bone defect in clinic. Here, a 3D printed enzyme-functionalized scaffold with multiple bioactivities including osteogenesis, angiogenesis, and anti-inflammation in diabetic conditions is proposed. The as-prepared multifunctional scaffold is constituted with alginate, glucose oxidase (GOx), and catalase-assisted biomineralized calcium phosphate nanosheets (CaP@CAT NSs). The GOx inside scaffolds can alleviate the hyperglycemia environment by catalyzing glucose and oxygen into gluconic acid and hydrogen peroxide (H2O2). Both the generated H2O2 as well as the overproduced H2O2 in DM can be scavenged by CaP@CAT NSs, while the initiated hypoxic microenvironment stimulates neovascularization. Moreover, the incorporation of CaP@CAT NSs not only enhance the mechanical property of the scaffolds, but also facilitate bone regeneration by the degraded Ca2+ and PO43− ions. The remarkable in vitro and in vivo outcomes demonstrate that enzymes functionalized scaffolds can be an effective strategy for enhancing bone tissue regeneration in diabetic conditions, underpinning the potential of multifunctional scaffolds for diabetic bone regeneration.  相似文献   

8.
Despite wide applications of bone morphogenetic protein–2 (BMP‐2), there are few methods to incorporate BPM‐2 within polymeric scaffolds while maintaining biological activity. Solid free‐form fabrication (SFF) of tissue‐engineering scaffold is successfully carried out with poly(lactic‐co‐glycolic acid) grafted hyaluronic acid (HA‐PLGA) encapsulating intact BMP‐2/poly(ethylene glycol) (PEG) complex. HA‐PLGA conjugate is synthesized in dimethyl sulfoxide (DMSO) by the conjugation reaction of adipic acid dihydrazide modified HA (HA‐ADH) and PLGA activated with N,N′‐dicyclohexylcarbodiimide (DCC) and N‐hydroxysuccinimide (NHS). BMP‐2 is complexed with PEG, which is encapsulated within the PLGA domain of the HA‐PLGA conjugate by SFF to prepare tissue‐engineering scaffolds. In vitro release tests confirm the sustained release of intact BMP‐2 from the scaffolds for up to a month. After confirmation of the enhanced osteoblast cell growth, and high gene‐expression levels of alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX) in the cells, the HA‐PLGA/PEG/BMP‐2 scaffolds are implanted into calvarial bone defects of Sprague Dawley (SD) rats. Microcomputed tomography (μCT) and histological analyses with Masson's trichrome, and hematoxylin and eosin (H&E) staining reveal effective bone regeneration on the scaffolds of HA‐PLGA/PEG/BMP‐2 blends.  相似文献   

9.
Malignant bone tumor is one of the major bone diseases. The treatment of such a bone disease typically requires the removal of bone tumor and regeneration of tumor‐initiated bone defects simultaneously. To address this issue, it is required that implanted biomaterials should combine the bifunctions of both therapy and regeneration. In this work, a bifunctional graphene oxide (GO)‐modified β‐tricalcium phosphate (GO‐TCP) composite scaffold combining a high photothermal effect with significantly improved bone‐forming ability is prepared by 3D‐printing and surface‐modification strategies. The prepared GO‐TCP scaffolds exhibit excellent photothermal effects under the irradiation of 808 nm near infrared laser (NIR) even at an ultralow power density of 0.36 W cm?2, while no photothermal effects are observed for pure β‐TCP scaffolds. The photothermal temperature of GO‐TCP scaffolds can be effectively modulated in the range of 40–90 °C by controlling the used GO concentrations, surface‐modification times, and power densities of NIR. The distinct photothermal effect of GO‐TCP scaffolds induces more than 90% of cell death for osteosarcoma cells (MG‐63) in vitro, and further effectively inhibits tumor growth in mice. Meanwhile, the prepared GO‐TCP scaffolds possess the improved capability to stimulate the osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) by upregulating bone‐related gene expression, and significantly promote new bone formation in the bone defects of rabbits as compared to pure β‐TCP scaffolds. These results successfully demonstrate that the prepared GO‐TCP scaffolds have bifunctional properties of photothermal therapy and bone regeneration, which is believed to pave the way to design and fabricate novel implanting biomaterials in combination of therapy and regeneration functions.  相似文献   

10.
Tissue-engineered scaffolds have been extensively explored for treating bone defects; however, slow and insufficient vascularization throughout the scaffolds remains a key challenge for further application. Herein, a versatile microfluidic 3D printing strategy to fabricate black phosphorus (BP) incorporated fibrous scaffolds with photothermal responsive channels for improving vascularization and bone regeneration is proposed. The thermal channeled scaffolds display reversible shrinkage and swelling behavior controlled by near-infrared irradiation, which facilitates the penetration of suspended cells into the scaffold channels and promotes the prevascularization. Furthermore, the embedded BP nanosheets exhibit intrinsic properties for in situ biomineralization and improve in vitro cell proliferation and osteogenic differentiation. Following transplantation in vivo, these channels also promote host vessel infiltration deep into the scaffolds and effectively accelerate the healing process of bone defects. Thus, it is believed that these near-infrared responsive channeled scaffolds are promising candidates for tissue/vascular ingrowth in diverse tissue engineering applications.  相似文献   

11.
The difficulty in spinal cord regeneration is related to the inhibitory factors for axon growth and the lack of appropriate axon guidance in the lesion region. Here scaffolds are developed with aligned nanofibers for nerve guidance and drug delivery in the spinal cord. Blended polymers including poly(L ‐lactic acid) (PLLA) and poly(lactide‐co‐glycolide) (PLGA) are used to electrospin nanofibrous scaffolds with a two‐layer structure: aligned nanofibers in the inner layer and random nanofibers in the outer layer. Rolipram, a small molecule that can enhance cAMP (cyclic adenosine monophosphate) activity in neurons and suppress inflammatory responses, is immobilized onto nanofibers. To test the therapeutic effects of nanofibrous scaffolds, the nanofibrous scaffolds loaded with rolipram are used to bridge the hemisection lesion in 8‐week old athymic rats. The scaffolds with rolipram increase axon growth through the scaffolds and in the lesion, promote angiogenesis through the scaffold, and decrease the population of astrocytes and chondroitin sulfate proteoglycans in the lesion. Locomotor scale rating analysis shows that the scaffolds with rolipram significantly improved hindlimb function after 3 weeks. This study demonstrates that nanofibrous scaffolds offer a valuable platform for drug delivery for spinal cord regeneration.  相似文献   

12.
13.
A novel cell isolation and release platform using electrospun polystyrene‐poly(styrene‐co‐maleic anhydride) (PS‐PSMA) nanofibers is presented. Ethanol treatment of PS‐PSMA nanofibers, employed for the purpose of sterilization, significantly increases their inter‐fiber space for both antibody conjugation and subsequent cell separation. For the selective isolation of CD4+ T cells from heterogeneous mixtures of mouse lymph nodes, capture efficiencies of up to 100% are achieved while maintaining cellular integrity and viability. Once captured, CD4+ T lymphocytes can also be released from the NF scaffolds, further demonstrating its potential functionality as an immune cell‐supporting and releasing matrix. This is the first demonstration of lymphocyte‐culture scaffolds enabling selective isolation, accommodation, and sustained release of CD4+ T cells for the purpose of cell therapies.  相似文献   

14.
Critical-sized bone defects, especially for irregular shapes, remain a significant challenge in orthopedics. Although various biomaterials are developed for bone regeneration, their application for repair of irregular bone defects is limited by the complicated preparation procedures involved, and their lack of shape-adaptive capacity, physiological adhesion, and potent osteogenic bioactivity. In the present study, a simple strategy of precipitation by introducing tannic acid (TA) with abundant phenolic hydroxyl groups and Fe3O4 nanoparticles, as metal-phenolic networks (MPN), is developed to easily prepare a fast gelling, shape-adaptive, and highly adhesive regenerated silk fibroin (RSF)/TA/Fe3O4 hydrogel system that can respond to a static magnetic field (SMF). The RSF/TA/Fe3O4 hydrogel exhibits sufficient adhesion in biological microenvironments and good osteogenic effect in vitro and in vivo, under an external SMF, and thus, can be applied to repair critical-sized bone defects. Moreover, bioinformatics analysis reveals that the synergistic mechanism of Fe3O4 NPs and SMF on osteogenic effects can be promotion of osteoblast differentiation via activation of the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)/extracellular signal-regulated kinase (ERK) signaling pathway. This study provides a promising biomaterial with potential clinical application for the future treatment of (irregular) critical-sized bone defects.  相似文献   

15.
Successful bone regeneration benefits from three‐dimensional (3D) bioresorbable scaffolds that mimic the hierarchical architecture and mechanical characteristics of native tissue extracellular matrix (ECM). A scaffold platform that integrates unique material chemistry with nanotopography while mimicking the 3D hierarchical bone architecture and bone mechanics is reported. A biocompatible dipeptide polyphosphazene‐polyester blend is electrospun to produce fibers in the diameter range of 50–500 nm to emulate dimensions of collagen fibrils present in the natural bone ECM. Various electrospinning and process parameters are optimized to produce blend nanofibers with good uniformity, appropriate mechanical strength, and suitable porosity. Biomimetic 3D scaffolds are created by orienting blend nanofiber matrices in a concentric manner with an open central cavity to replicate bone marrow cavity, as well as the lamellar structure of bone. This biomimicry results in scaffold stress–strain curve similar to that of native bone with a compressive modulus in the mid‐range of values for human trabecular bone. Blend nanofiber matrices support adhesion and proliferation of osteoblasts and show an elevated phenotype expression compared to polyester nanofibers. Furthermore, the 3D structure encourages osteoblast infiltration and ECM secretion, bridging the gaps of scaffold concentric walls during in vitro culture. The results also highlight the importance of in situ ECM secretion by cells in maintaining scaffold mechanical properties following scaffold degradation with time. This study for the first time demonstrates the feasibility of developing a mechanically competent nanofiber matrix via a biomimetic strategy and the advantages of polyphosphazene blends in promoting osteoblast phenotype progression for bone regeneration.  相似文献   

16.
Because cartilage and bone tissues have different lineage‐specific biological properties, it is challenging to fabricate a single type of scaffold that can biologically fulfill the requirements for regeneration of these two lineages simultaneously within osteochondral defects. To overcome this challenge, a lithium‐containing mesoporous bioglass (Li‐MBG) scaffold is developed. The efficacy and mechanism of Li‐MBG for regeneration of osteochondral defects are systematically investigated. Histological and micro‐CT results show that Li‐MBG scaffolds significantly enhance the regeneration of subchondral bone and hyaline cartilage‐like tissues as compared to pure MBG scaffolds, upon implantation in rabbit osteochondral defects for 8 and 16 weeks. Further investigation demonstrates that the released Li+ ions from the Li‐MBG scaffolds may play a key role in stimulating the regeneration of osteochondral defects. The corresponding mechanistic pathways involve Li+ ions enhancing the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) through activation of the Wnt signalling pathway, as well as Li+ ions protecting chondrocytes and cartilage tissues from the inflammatory osteoarthritis (OA) environment through activation of autophagy. These findings suggest that the incorporation of Li+ ions into bioactive MBG scaffolds is a viable strategy for fabricating bi‐lineage conducive scaffolds that enhance regeneration of osteochondral defects.  相似文献   

17.
Engineered and decellularized extracellular matrices (ECM) are receiving increasing interest in regenerative medicine as materials capable to induce cell growth/differentiation and tissue repair by physiological presentation of embedded cues. However, ECM production/decellularization processes and control over their composition remain primary challenges. This study reports engineering of ECM materials with customized properties, based on genetic manipulation of immortalized and death‐inducible human mesenchymal stromal cells (hMSC), cultured within 3D porous scaffolds under perfusion flow. The strategy allows for robust ECM deposition and subsequent decellularization by deliberate cell‐apoptosis induction. As compared to standard production and freeze/thaw treatment, this grants superior preservation of ECM, leading to enhanced bone formation upon implantation in calvarial defects. Tunability of ECM composition and function is exemplified by modification of the cell line to overexpress vascular endothelial growth factor alpha (VEGF), which results in selective ECM enrichment and superior vasculature recruitment in an ectopic implantation model. hMSC lines culture under perfusion‐flow is pivotal to achieve uniform scaffold decoration with ECM and to streamline the different engineering/decellularization phases in a single environmental chamber. The findings outline the paradigm of combining suitable cell lines and bioreactor systems for generating ECM‐based off‐the‐shelf materials, with custom set of signals designed to activate endogenous regenerative processes.  相似文献   

18.
Uncontrollable dendritic behavior and infinite volume expansion in alkali metal anode results in the severe safety hazards and short lifespan for high‐energy batteries. Constructing a stable host with superior Na/Li‐philic properties is a prerequisite for commercialization. Here, it is demonstrated that the small Gibbs free energy change in the reaction between metal oxide (Co3O4, SnO2, and CuO) and alkali metal is key for metal infusion. The as‐prepared hierarchical Co3O4 nanofiber–carbon sheet (CS) skeleton shows improved wettability toward molten Li/Na. The 3D carbon sheet serves as a primary framework, offering adequate lithium nucleation sites and sufficient electrolyte/electrode contact for fast charge transfer. The secondary framework of Co/Li2O nanofibers provides physical confinement of deposited Li and further redistributes the Li+ flux on each carbon fiber, which is verified by COMSOL Multiphysics simulations. Due to the uniform deposition behavior and near‐zero volume change, modified symmetrical Li/Li cells can operate under an ultrahigh current density of 20 mA cm?2 for more than 120 cycles. When paired with LiFePO4 cathodes, the Li/Co–CS cell shows low polarization and 88.4% capacity retention after 200 cycles under 2 C. Convincing improvement can also be observed in Na/Co–CS symmetrical cells applying NaClO4‐based electrolyte. These results illustrate a significant improvement in developing safe and stable alkali metal batteries.  相似文献   

19.
The regeneration of artificial bone substitutes is a potential strategy for repairing bone defects. However, the development of substitutes with appropriate osteoinductivity and physiochemical properties, such as water uptake and retention, mechanical properties, and biodegradation, remains challenging. Therefore, there is a motivation to develop new synthetic grafts that possess good biocompatibility, physiochemical properties, and osteoinductivity. Here, we fabricate a biocompatible scaffold through the covalent crosslinking of graphene oxide (GO) and carboxymethyl chitosan (CMC). The resulting GO‐CMC scaffold shows significant high water retention (44% water loss) compared with unmodified CMC scaffolds (120% water loss) due to a steric hindrance effect. The modulus and hardness of the GO‐CMC scaffold are 2.75‐ and 3.51‐fold higher, respectively, than those of the CMC scaffold. Furthermore, the osteoinductivity of the GO‐CMC scaffold is enhanced due to the π–π stacking interactions of the GO sheets, which result in striking upregulation of osteogenesis‐related genes, including osteopontin, bone sialoprotein, osterix, osteocalcin, and alkaline phosphatase. Finally, the GO‐CMC scaffold exhibits excellent reparative effects in repairing rat calvarial defects via the synergistic effects of GO and bone morphogenetic protein‐2. This study provides new insights for developing bone substitutes for tissue engineering and regenerative medicine.  相似文献   

20.
Highly porous electrode designs are often employed for photoelectrochemical energy conversion applications. “Inverse opal” structures generate high surface area electrodes to enhance light absorption in semiconductors with short carrier collection lengths, effectively increasing the optical depth of ultrathin film photoelectrodes. Here, the fabrication of hierarchically structured, “host–guest” photoelectrodes based on selective atomic layer deposition of ZnO in composite polystyrene–SiO2 nanosphere films is described. Nanostructured scaffolds for ultrathin film photoanodes are prepared with a facile, continuously tunable solution‐phase synthesis. The characteristic length scales for absorption, carrier collection, and mass transport can be independently engineered into the electrode by choosing appropriate colloidal components for the composite scaffold. 20 nm ZnO photoanode layers based on the “host–guest” architecture exhibit roughly 500 times the photocurrent generated on an equivalent planar electrode and a 430% increase over a photoanode structured by a scaffold comprised of a close‐packed assembly of identical SiO2 nanospheres. This results from an improved balance of reactant mass transport and the locus of light absorption throughout the electrode. This approach offers a facile route for preparing strategically nanostructured photoelectrodes based on strategies developed from more complex fabrication techniques.  相似文献   

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