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Mimicking the natural bone extracellular matrix containing intrinsic topography and electrical signals is an effective way to modulate bone regeneration. However, simultaneously coupling of the intrinsic mechanobiology and electrical cues of implant to modulate bone regeneration remains ignored. Here, the authors report in situ designation of titanium dioxide (TiO2) nanocone/bismuth oxide (Bi2O3) nanodot heterojunctions on bone implant surface to electro-biomechanically trigger osseointegration at bone/implant interface. TiO2 nanocone/Bi2O3 nanodot heterojunctions exhibit built-in electric field at the nanoscale interface and elastic modulus equivalent to that of bone tissue. The nano-heterojunctions significantly promoted the attachment, spreading, and osteogenic differentiation of bone marrow mesenchymal stem cells in vitro, and the osteogenesis in vivo. The authors also show that the effects of nano-heterojunctions on osteogenesis are mediated by yes-associated protein biomechanical signal pathway and intracellular enrichment induced Phosphatidylinositol 3-kinase signal pathway. Their findings highlight the coupling of topographical and electric parameters of biomaterials for modulating cell behaviors.  相似文献   

3.
Abnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede bone repair processes. Herein, an innovative ultrasound-modulatable hydrogel platform with selenoprotein-mediated antioxidant effects to promote bone injury repair is presented. This hydrogel platform encapsulates oxygen-enriched selene-incorporated thin-shell silicon within methacrylate gelatin (O2-PSSG). The resultant construct orchestrates the modulation of the bone-defect microenvironment, thereby expediting the course of bone regeneration. Ultrasound (US) is used to regulate the pore size of the hydrogel to release selenium-containing nanoparticles and promote the in situ synthesis of efficient intracellular selenoproteins and hydrogen peroxide consumption. As expected, O2-PSSG rapidly releases selenocystine ([Sec]2) under US control to scavenge reactive oxygen species and maintain the homeostasis of bone marrow mesenchymal stem cells (BMSCs). Over time, the action of the system by selenoprotein increases the activation of Wnt/β-catenin pathways and promotes the differentiation of BMSCs. Consequently, O2-PSSG potentiates the antioxidant proficiency of BMSCs both in vitro and in vivo, alleviates hypoxic environments, promotes osteogenic differentiation, and expedites cranial bone repair in rat models. In summary, this study suggests that the designed and constructed US-responsive antioxidant hydrogel is a promising prospective strategy for addressing bone defects and fostering bone regeneration.  相似文献   

4.
Human bone tissue is built in a hierarchical way by assembling various cells of specific functions; the behaviors of these cells in vivo are sophisticatedly regulated. However, the cells in an injured bone caused by tumor or other bone‐related diseases cannot properly perform self‐regulation behaviors, such as specialized differentiation. To address this challenge, a simple one‐step strategy for patterning drug‐laden poly(lactic‐co‐glycolic acid) (PLGA) microspheres into grooves by Teflon chips is developed to direct cellular alignment and osteogenic commitment of adipose‐derived stem cells (ADSCs) for bone regeneration. A hydrophilic model protein and a hydrophobic model drug are encapsulated into microsphere‐based grooved micropatterns to investigate the release of the molecules from the PLGA matrix. Both types of molecules show a sustained release with a small initial burst during the first couple of days. Osteogenic differentiated factors are also encapsulated in the micropatterns and the effect of these factors on inducing the osteogenic differentiation of ADSCs is studied. The ADSCs on the drug‐laden micropatterns show stronger osteogenic commitment in culture than those on flat PLGA film or on drug‐free grooved micropatterns cultured under the same conditions. The results demonstrate that a combination of chemical and topographical cues is more effective to direct the osteogenic commitment of stem cells than either is alone. The microsphere‐based groove micropatterns show potential for stem cell research and bone regenerative therapies.  相似文献   

5.
Guided bone regeneration (GBR) technology is the most widely used and stable method for bone defect repair. However, infectious bone defect limits the application of this technique. Herein, a small intestinal submucosa (SIS) membrane modified by chimeric peptides as a new type of GBR membrane is developed for efficacious tissue regeneration. Based on the main components of SIS membrane are I and III collagen, collagen binding peptides TKKTLRT and KELNLVY sequences are used to construct chimeric peptides with healing-promoting peptide Hst1 or antibacterial osteogenic peptide JH8194, so as to realize the specifically target of SIS. This method achieves the fast and efficient multifunctional modification of SIS membrane. The chimeric peptides modified SIS (pSIS) membrane has satisfactory biocompatibility and a certain degree of antibacterial activity. Moreover, pSIS promotes the osteogenic related factors expression of rat bone mesenchymal stem cells and demonstrates great bone regeneration in rat skull defect model. Furthermore, pSIS accelerates the migration of oral epithelial cells in vitro and activate integrin α3β1 signal pathway contribute to wound healing. This study presents a novel biomaterial design of GBR membrane, specifically for the treatment of infectious bone defects.  相似文献   

6.
Building of multifunctional coatings in a more effective way is crucial for meeting the multilevel requirements of regenerative medicine. Herein, inspired by diatom and mussel, a specific but universal approach is proposed for building multifunctional coatings on slow-degradable and fast-degradable scaffolds or various substrates by using epigallocatechin gallate (EGCG) and polyethyleneimine (PEI) as bridges of silicon coupling. The results reveal that the polyphenol EGCG facilitates silica precipitation and coating topological morphology in synergy with PEI, and realizes antioxidant and immunomodulatory effects. The introduction of EGCG and the release of silicon ions present effective modulation of the immune microenvironment and remarkable promotion of angiogenesis and osteogenesis. The EGCG/silica coating strategy demonstrates a promising perspective for designing multifunctional coatings and optimizing tissue regeneration and reconstruction.  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.
Realizing the clinical potential of human induced pluripotent stem cells (hiPSCs) in bone regenerative medicine requires the development of safe and chemically defined biomaterials for expansion of hiPSCs followed by directing their lineage commitment to osteoblasts. In this study, novel multipurpose peptide‐presenting hydrogel surfaces are prepared on common tissue culture plates via carboxymethyl chitosan grafting and subsequent immobilization of two functional peptides allowing for in vitro feeder‐free culture, long‐term self‐renewal, and osteogenic induction of hiPSCs. After vitronectin (VN) peptide modification, the engineered surfaces facilitate adhesion, proliferation, colony formation, and the maintenance of pluripotency of hiPSCs up to passage 10 under fully defined conditions without Matrigel or protein coating. Further, this synthetic niche exhibits an appealing regulatory effect on the osteogenic conversion of hiPSCs to osteoblastic phenotype without an embryoid body formation step by co‐decoration of different ratios of VN and bone‐forming peptide. Such a well‐defined, xeno‐free 2D engineered microenvironment not only helps to accelerate the clinical development of hiPSCs, but also provides a safe and robust platform for the generation of osteoblast‐like cells or bone‐like tissues at different maturation levels. Thus, the strategy may hold great potential for application in cell therapy and bone tissue engineering.  相似文献   

9.
Effective antitumor agents with concurrent osteogenic properties are essential for comprehensive osteosarcoma (OS) treatment. However, the current clinical therapeutic strategies of OS fail to completely eradicate tumors while simultaneously encouraging bone formation. To address this issue, a switchable strategy for dynamic OS ablation and static bone regeneration is developed by integrating piezoelectric BaTiO3 (BTO) with atomic-thin Ti3C2 (TC) through a Schottky heterojunction, resulting in the formation of TC@BTO. Under sequential ultrasound and near-infrared irradiation, the optimized carrier transport of TC@BTO, based on Schottky heterojunction, exhibits excellent characteristics of photothermal conversion and reactive oxygen species generation. This results in ferroptosis of tumor cells and eventual elimination of OS. Moreover, in the static state, the interfacial Schottky heterojunction facilitates the carriers’ directed transfer from the semiconductor to the metal. The Schottky heterojunction-enhanced static electrical stimulation enhances the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and repair of bone defects. Furthermore, RNA-sequencing analysis reveals that static TC@BTO promotes bone regeneration by activating Wnt signaling pathway, and remarkably, pharmacological inhibition of Wnt signaling suppresses the TC@BTO-induced osteogenesis. Overall, this work broadens the biomedical potential of Schottky heterojunction-based therapies and provides a comprehensive strategy for overall OS ablation and bone regeneration.  相似文献   

10.
Clinically, cartilage damage is frequently accompanied with subchondral bone injuries caused by disease or trauma. However, the construction of biomimetic scaffolds to support both cartilage and subchondral bone regeneration remains a great challenge. Herein, a novel strategy is adopted to realize the simultaneous repair of osteochondral defects by employing a self‐assembling peptide hydrogel (SAPH) FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine) to coat onto 3D‐printed polycaprolactone (PCL) scaffolds. Results show that the SAPH‐coated PCL scaffolds exhibit highly improved hydrophilicity and biomimetic extracellular matrix (ECM) structures compared to PCL scaffolds. In vitro experiments demonstrate that the SAPH‐coated PCL scaffolds promote the proliferation and osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) and maintain the chondrocyte phenotypes. Furthermore, 3% SAPH‐coated PCL scaffolds significantly induce simultaneous regeneration of cartilage and subchondral bone after 8‐ and 12‐week implantation in vivo, respectively. Mechanistically, by virtue of the enhanced deposition of ECM in SAPH‐coated PCL scaffolds, SAPH with increased stiffness facilitates and remodels the microenvironment around osteochondral defects, which may favor simultaneous dual tissue regeneration. These findings indicate that the 3% SAPH provides efficient and reliable modification on PCL scaffolds and SAPH‐coated PCL scaffolds appear to be a promising biomaterial for osteochondral defect repair.  相似文献   

11.
An ideal guided bone regeneration membrane (GBRM) is expected not only to perform barrier function, but also to enhance osteogenesis and resist bacteria infection. However, currently available membranes have limited bioactivities. To address this challenge, a Janus GBRM (JGM) is designed and fabricated by sequential fractional electrospinning here. The random gelatin fibers loaded with hydroxyapatite (HAP) are designed as the inner face to promote the osteoblasts’ adhesion, proliferation, and osteogenic differentiation, meanwhile the aligned poly(caprolactone) (PCL) nanofibers loaded with poly(methacryloxyethyltrimethyl ammonium chloride-co-2-Aminoethyl 2-methylacrylate hydrochloride) (P(DMC-AMA)) are designed as the outer layer to resist epithelia invasion and bacterial infection. In vitro assays reveal that the inner face displays enhanced osteogenic effects, meanwhile the outer surface can regulate the epithelia to spread along the aligned direction and kill the contacted bacteria. Interestingly, the outer face can induce macrophages to polarize toward the M2 phenotype, thus manipulating a favorable osteoimmune environment. These results suggest that the JGM simultaneously meets the critical requirements of barrier, osteogenic, antibacterial, and osteoimmunomodulatory functions. Consequently, the JGM shows better in vivo bone tissue regeneration performance than the commercial Bio-Gide membrane. This work provides a novel platform to design multi-functional membranes/scaffolds, displaying great potential applications in tissue engineering.  相似文献   

12.
The development of biomimetic bone matrices is one of the major goals in the bone‐regeneration and tissue‐engineering fields. Nanocomposites consisting of a natural polymer and hydroxyapatite (HA) nanocrystals, which mimic the human bone matrix, are thus regarded as promising bone regenerative materials. Herein, we developed a biomimetic nanocomposite with a novel nanofibrous structure by employing an electrospinning (ES) method. The HA precipitate/gelatin matrix nanocomposites are lyophilized and dissolved in an organic solvent, and then electrospun under controlled conditions. With this process, we can successfully generate a continuous fiber with a diameter of the order of hundreds of nanometers. The internal structure of the nanofiber features a typical nanocomposite, i.e., HA nanocrystals well distributed within a gelatin matrix. These nanocomposite fibers improve the bone‐derived cellular activity significantly when compared to the pure gelatin equivalent. This method of generating a nanofiber of the biomimetic nanocomposite was effective in producing a biomedical membrane with a composition gradient, which is potentially applicable in the field of guided tissue regeneration (GTR).  相似文献   

13.
Dysfunctional macrophages and excessive inflammatory responses lead to severe tissue regeneration disorders in diabetes. Herein, a function-oriented self-amplification immunomodulatory (SAI) strategy based on an interleukin-33 (IL-33) loaded zeolitic imidazolate frameworks (IL@ZIF) nano-platform is proposed to treat tissue regeneration disorders by restoring macrophage function and reconstructing immune microenvironment in diabetes. It is found that ZIFs effectively protect IL-33 from premature degradation. In the wound area, the released Zn2+ not only improves the antioxidant capacity of macrophages to avoid reactive oxygen species-induced dysfunction, but also upregulates IL-33 receptor (ST2L) expression and triggers M2 macrophages polarization. Subsequently, the released IL-33 significantly amplifies M2 macrophage polarization through IL-33/ST2L signaling, resulting in a reversal of the pro-inflammatory microenvironment of diabetic wounds. This synergistic effect endows the nano-platform with an excellent ability to accelerate tissue regeneration in vitro and in vivo. Overall, this IL@ZIF mediated function-oriented SAI strategy provides new alternatives for the treatment of tissue regeneration disorders in diabetes.  相似文献   

14.
Delivery of biofactors in a precise and controlled fashion remains a clinical challenge. Stimuli‐responsive delivery systems can facilitate “on‐demand” release of therapeutics in response to a variety of physiologic triggering mechanisms (e.g., pH, temperature). However, few systems to date have taken advantage of mechanical inputs from the microenvironment to initiate drug release. Here, mechanically activated microcapsules (MAMCs) are designed to deliver therapeutics in response to the mechanically loaded environment of regenerating musculoskeletal tissues, with the ultimate goal of furthering tissue repair. To establish a suite of microcapsules with different thresholds for mechanoactivation, MAMC physical dimensions and composition are first manipulated, and their mechano‐response under both direct 2D compression and in 3D matrices mimicking the extracellular matrix properties and dynamic loading environment of regenerating tissue, is evaluated. To demonstrate the feasibility of this delivery system, an engineered cartilage model is used to test the efficacy of mechanically instigated release of transforming growth factor‐β3 on the chondrogenesis of mesenchymal stem cells. These data establish a novel platform by which to tune the release of therapeutics and/or regenerative factors based on the physiologic mechanical loading environment and will find widespread application in the repair and regeneration of musculoskeletal tissues.  相似文献   

15.
Rapid and efficient disease‐induced or critical‐size bone regeneration remains a challenge in tissue engineering due to the lack of highly bioactive biomaterial scaffolds. Physical structures such as nanostructures, chemical components such as silicon elements, and biological factors such as genes have shown positive effects on bone regeneration. Herein, a bioactive photoluminescent elastomeric silicate‐based nanofibrous scaffold with sustained miRNA release is reported for promoting bone regeneration based on a joint physico‐chemical‐biological strategy. Bioactive nanofibrous scaffolds are fabricated by cospinning poly (ε‐caprolactone) (PCL), elastomeric poly (citrates‐siloxane) (PCS), and bioactive osteogenic miRNA nanocomplexes (denoted PPM nanofibrous scaffolds). The PPM scaffolds possess uniform nanostructures, significantly enhanced tensile stress (≈15 MPa) and modulus (≈32 MPa), improved hydrophilicity (30–60°), controlled biodegradation, and strong blue fluorescence. Bioactive miRNA complexes are efficiently loaded into the nanofibrous matrix and exhibit long‐term release for up to 70 h. The PPM scaffolds significantly promote the adhesion, proliferation, and osteoblast differentiation of bone marrow stem cells in vitro and enhanced rat cranial defect restoration (12 weeks) in vivo. This work reports an attractive joint physico‐chemical‐biological strategy for the design of novel cell/protein‐free bioactive scaffolds for synergistic tissue regeneration.  相似文献   

16.
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   

17.
Currently, diabetic infectious wound treatments remain a significant challenge for regenerative medicine due to the unicity of clinical dressings, which lack systemic multifunctional wound dressings with high absorbability, customizable shape, rapid self-healing, guiding tissue regeneration, and restoring physiological functions. Here, a multifunctional DNA hydrogel is conveniently obtained through grafting DNA units and polyethyleneimine dynamic cross-linking and doped heating function black phosphorus quantum dots. The obtained DNA hydrogel features excellent exudate absorption performance, adjustable heating ability, mechanical behavior, self-healing ability, writability, tissue adhesion, and antibacterial properties. The incorporation of procyanidin B2 (OPC B2) endows the DNA hydrogels with renowned scavenging free radicals and antioxidant properties. Furthermore, the DNA hydrogel dressing can promote the transformation of macrophages from pro-inflammatory M1 into repairing M2 phenotype, keeping the wound in a stable remodeled state. Astonishingly, the DNA hydrogel dressing can activate neurons to transform into a repair state, accelerating skin nerve regeneration and angiogenesis. Beyond that, it can recruit myeloid cells to activate the adaptive immune response, enhancing the ability of DNA hydrogel dressing to promote tissue regeneration, thereby promoting hair follicle and hair regeneration. Therefore, this advanced collaborative strategy provides an effective method for cascade management of clinical guided tissue regeneration.  相似文献   

18.
The osteoimmunology has revealed that immune system plays an important role in maintaining bone metabolism and remodeling. As long-term physiological factor in bone, mechanical stimulation such as micro-vibration stimulation (MVS) exerts effects on regulating osteogenesis and immune response. In this study, the osteo-immunodulatory effects of bicalcium phosphate (BCP) ceramics coupled with MVS are investigated. This results find that the combination of BCP ceramics and MVS may exert synergistic effects on the polarization and functional status of macrophages through activating plasma membrance Ca2+ ATPase (PMCA) channel, reducing the intracellular calcium ion concentration, and inhibiting downstream extracellular signal-regulated kinase (ERK)1/2 signaling pathway. BCP ceramics coupled MVS could drive the macrophage polarization to wound-healing M2 phenotype to decrease the production of pro-inflammatory factors, enhance the secretion of anti-inflammatory cytokines and growth factors such as transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2. Moreover, BCP and MVS-modulated macrophage secretion pattern can trigger the BMP/TGF-Smad signaling pathways to induce osteoblastic differentiation of bone marrow mesenchymal stromal cells (BM-MSCs) in vitro, and maintain cellular viability and promote the formation of collagen-rich osteoid like tissues and mature blood vessels in vivo. This study demonstrates that the introduction of mechanical stimuli like non-invasive MVS is an effective strategy to improve bone repair effects of biomaterials through endowing them with superior osteo-immunodulatory capacity.  相似文献   

19.
Despite numerous attempts to engineer cartilage tissue in recent years, significant challenges remain regarding hyaline cartilage regeneration. One main reason is that the overactivated inflammatory response after injury suppresses inherent cartilage regenerative capabilities. Since the arthritic microenvironment is constantly changing during posttraumatic stress, an inflammatory diagnostic logic-based hydrogel for cartilage regeneration is developed for the first time through cross-linking of 4-arm poly(ethylene glycol)-vinyl sulfone (PEG-VS) and specific matrix metalloproteinase (MMP) 13-sensitive peptides. The hydrogel exhibits diagnostic logic to identify the pathological cue MMP13 and accordingly determine drug release kinetics in an inflammatory microenvironment. Additionally, multiphase therapeutic ability is designed to program different cargo release behaviors to match the inflammation-chondrogenesis cascade for better cartilage regeneration. Here, it is first proposed that MMP13 is a suitable diagnostic biomarker to modulate the inflammatory microenvironment in the early stage of cartilage injury. In vitro and in vivo studies show that the hydrogel has good injectability, on-demand anti-inflammation, and immunomodulation capabilities. Ultimately, loaded with multiple therapeutic factors, the hydrogel shows both microenvironmental modulation and chondrogenesis therapeutic ability, resulting in satisfactory hyaline cartilage regeneration. This study provides critical insight into the design and biological mechanism of both diagnostic and therapeutic ability-based cartilage tissue engineering strategies.  相似文献   

20.
Skeletal tissue regeneration is often required following trauma, where substantial bone or cartilage loss may be encountered and is a significant driver for the development of biomaterials with a defined 3D structural network. Solvent blending is a process that avoids complications associated with conventional thermal or mechanical polymer blending or synthesis, opening up large areas of chemical and physical space, while potentially simplifying regulatory pathways towards in vivo application. Here ternary mixtures of natural and synthetic polymers were solvent blended and evaluated as potential bone tissue engineering matrices for osteoregeneration by the assessment of growth and differentiation of STRO‐1+ skeletal stem cells. Several of the blend materials were found to be excellent supports for human bone marrow‐derived STRO‐1+ skeletal cells and fetal skeletal cells, with the optimized blend exhibiting in vivo osteogenic potential, suggesting that these polymer blends could act as suitable matrices for bioengineering of hard tissues.  相似文献   

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