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1.
Development of new therapeutic scaffolds to selectively destruct tumors under gentle conditions meanwhile promoting adipose tissue formation would be a promising strategy for clinical treatment of breast cancer. Herein, a stimuli‐responsive scaffold composed of polyacrylic acid‐g‐polylactic acid (PAA‐g‐PLLA) modified graphene oxide (GO) with a cleavable bond in between (GO‐PAA‐g‐PLLA), gambogic acid (GA), and polycaprolactone (PCL) is fabricated and then preseeded on adipose‐derived stem cells (ADSCs) for breast cancer treatment. This GO–GA‐polymer scaffold is able to simultaneously perform pH‐triggered low temperature (45 °C) photothermal therapy to selectively induce the apoptosis of tumor cells and significantly improve ADSCs growth without any photothermal damage. The low‐temperature photothermal therapy of the scaffolds can induce more than 95% of cell death for human breast cancer (MCF‐7) in vitro, which further completely inhibits tumor growth and finally eliminates tumor tissue in mice. Meanwhile, the prepared GO–GA‐polymer scaffold possesses the improved capability to stimulate the differentiation of ADSCs into adipocytes by upregulating adipo‐related gene expression, and significantly promotes new adipose tissue formation whether with or without NIR irradiation. These results successfully demonstrate that the prepared GO–GA‐polymer scaffolds with bifunctional properties will be a promising candidate for clinical cases involving both tumor treatment and tissue engineering.  相似文献   

2.
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   

3.
Malignant bone tumors are one of the major serious diseases in clinic. Inferior reconstruction of new bone and rapid propagation of residual tumor cells are the main challenges to surgical intervention. Herein, a bifunctional DTC@BG scaffold for near‐infrared (NIR)‐activated photonic thermal ablation of osteosarcoma and accelerated bone defect regeneration is engineered by in situ growth of NIR‐absorbing cocrystal (DTC) on the surface of a 3D‐printing bioactive glass (BG) scaffold. The prominent photothermal conversion performance and outstanding bone regeneration capability of DTC@BG scaffolds originate from the precise tailoring of the bandgap between the electron donors and acceptors of DTC and promote new bone growth performance of BG scaffolds. DTC@BG scaffolds not only significantly promote tumor cell ablation in vitro, but also effectively facilitate bone tumor suppression in vivo. In particular, DTC@BG scaffolds exhibit excellent capability in stimulating osteogenic differentiation and angiogenesis, and finally promote newborn bone formation in the bone defects. This research represents the first paradigm for ablating osteosarcoma and facilitating new bone formation through precise modulation of electron donors and acceptors in the cocrystal, which offers a new avenue to construct high‐efficiency therapeutic platforms based on cocrystal strategy for ablation of malignant bone tumor.  相似文献   

4.
Stimuli‐responsive anticancer agents are of particular interest in the field of cancer therapy. Nevertheless, so far stimuli‐responsive photothermal agents have been explored with limited success for cancer photothermal therapy (PTT). In this work, as a proof‐of‐concept, a pH‐responsive photothermal nanoconjugate for enhanced PTT efficacy, in which graphene oxide (GO) with broad NIR absorbance and effective photothermal conversion efficiency is selected as a typical model receptor of fluorescence resonance energy transfer (FRET), and grafted cyanine dye (e.g., Cypate) acts as the donor of near‐infrared fluorescence (NIRF), is reported for the first time. The conjugate of Cypate‐grafted GO exhibits different conformations in aqueous solutions at various pH, which can trigger pH‐dependent FRET effect between GO and Cypate and thus induce pH‐responsive photothermal effect of GO‐Cypate. GO‐Cypate exhibits severe cell damage owing to the enhanced photothermal effect in lysosomes, and thus generate synergistic PTT efficacy with tumor ablation upon photoirradiation after a single‐dose intravenous injection. The photothermal nanoconjugate with broad NIR absorbance as the effective receptor of FRET can smartly convert emitted NIRF energy from donor cyanine dye into additional photothermal effect for improving PTT. These results suggest that the smart nanoconjugate can act as a promising stimuli‐responsive photothermal nanoplatform for cancer therapy.  相似文献   

5.
The surgical procedure in skin‐tumor therapy usually results in cutaneous defects, and multidrug‐resistant bacterial infection could cause chronic wounds. Here, for the first time, an injectable self‐healing antibacterial bioactive polypeptide‐based hybrid nanosystem is developed for treating multidrug resistant infection, skin‐tumor therapy, and wound healing. The multifunctional hydrogel is successfully prepared through incorporating monodispersed polydopamine functionalized bioactive glass nanoparticles (BGN@PDA) into an antibacterial F127‐ε‐Poly‐L‐lysine hydrogel. The nanocomposites hydrogel displays excellent self‐healing and injectable ability, as well as robust antibacterial activity, especially against multidrug‐resistant bacteria in vitro and in vivo. The nanocomposites hydrogel also demonstrates outstanding photothermal performance with (near‐infrared laser irradiation) NIR irradiation, which could effectively kill the tumor cell (>90%) and inhibit tumor growth (inhibition rate up to 94%) in a subcutaneous skin‐tumor model. In addition, the nanocomposites hydrogel effectively accelerates wound healing in vivo. These results suggest that the BGN‐based nanocomposite hydrogel is a promising candidate for skin‐tumor therapy, wound healing, and anti‐infection. This work may offer a facile strategy to prepare multifunctional bioactive hydrogels for simultaneous tumor therapy, tissue regeneration, and anti‐infection.  相似文献   

6.
Silk fibroin (SF) has attracted great interest in bone tissue engineering due to its extraordinary characteristics in terms of mechanical properties, biocompatibility, and biodegradability. SF scaffolds are assembled by biocompatible polydopamine nanoparticles at mesoscopic scale, which endows the scaffolds with a near-infrared (NIR) light response for the treatment of bone tumors. The functionalized SF scaffold not only enhances the significant structure and performance of native SF scaffold for bone treatment and reconstruction, such as primary and mesoscopic structure, multi-level pores, and biodegradation, as well as biocompatibility but also have excellent photothermal effect leading a significant cytotoxicity to MG63 cancer cells after NIR laser irradiation. Moreover, the penetration of NIR light in tissue is improved using an optical fiber, which demonstrates the obtained scaffolds’ great potential in the application of photothermal therapy.  相似文献   

7.
A major hindrance to successful alveolar bone augmentation and ridge preservation using synthetic scaffolds is insufficient vascularization in the implanted bone grafts. The slow ingrowth of host vasculature from the bone bed of alveolar bone to the top of the implanted bone grafts leads to limited bone formation in the upper layers of the implanted grafts, which hinders the subsequent implantation of titanium dental implants. In this study, macroporous beta‐tricalcium phosphate (β‐TCP) scaffolds with multiple vertical hollow channels are fabricated that play a similar role as blood vessels for nutrient diffusion and cell migration. The results show that the hollow channels accelerate the degradation rate of the β‐TCP scaffolds and the in vitro release of a bone forming peptide‐1, which significantly promote proliferation and osteogenesis of human bone mesenchymal stem cells on the channeled scaffolds, compared to nonchanneled scaffolds in vitro. More volume of newly formed bone tissues with more blood vessels are augmented in the channeled scaffolds when implanted in mandibular bone defects of beagle dogs. Channeled scaffolds significantly promote new bone formation and augment the height of the mandible. These findings indicate channeled scaffolds facilitate vascularization and bone formation and have great potential for vascularized bone augmentation.  相似文献   

8.
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   

9.
All tissues and organs can be affected by diseases, and treatments for these diseases can cause damage to surrounding healthy tissues and organs. Therefore, treatment is required that involves disease therapy alongside tissue/organ regeneration. The design, construction, and biomedical applications of biomaterial platforms with both disease‐therapeutic and tissue‐regeneration multifunctionalities are in demand, which are herein referred to as theragenerative (abbreviation of therapy and regeneration) biomaterials. Due to the rapid development of theragenerative biomaterials in versatile biomedical applications, this progress report aims to summarize, discuss, and highlight the rational construction of distinctive theragenerative biomaterials with intrinsic therapeutic performance and tissue‐regeneration bioactivity. Based on the intrinsic response to either external physical triggers (e.g., photonic response or magnetic‐field response) or endogenous disease microenvironments (e.g., mild acidity or overexpressed hydrogen peroxide) and tissue‐regeneration bioactivity, these theragenerative biomaterials are extensively explored in various biomedical fields, including bone‐tumor therapy/regeneration, bone antibacterial therapy/regeneration, skin‐tumor therapy/regeneration, skin antibacterial therapy/regeneration, breast‐tumor therapy/adipose‐tissue regeneration, and osteoarticular‐tuberculosis therapy/bone‐tissue regeneration. The challenges faced and future developments of these distinctive theragenerative biomaterials are discussed, as are methods for further promoting their clinical translation.  相似文献   

10.
Malignant bone tumors are often accompanied by osteolytic destruction and severe pathological fractures. Current therapeutic strategies can largely inhibit tumor proliferation, but the high recurrence rate of tumors and related bone defects remain a significant challenge. This study aims to address these issues by developing a novel near-infrared (NIR) light-responsive and a mechanically strong hydrogel that offers excellent photothermal tumor therapy and bone fracture repair capabilities. The as-prepared hydrogel exhibits good biocompatibility and an ultra-strong photothermal effect due to the formation of a complex network with up-conversion lanthanide-Au hybrid nanoparticles and alginate molecules. A subcutaneous tumor model is used to demonstrate that tumors can be efficiently eradicated via local photothermal treatment, where there is no tumor recurrence within the observation period. Moreover, the injected hydrogel becomes mechanically strong due to in situ Ca2+ crosslinking, which provides a supportive matrix to promote the repair of bone defects via stabilization of the fractured bone structure. The high photothermal effect and robust support offered by this single material demonstrate the potential of using the proposed hydrogel for the simultaneous treatment of bone tumor removal and bone healing.  相似文献   

11.
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   

12.
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   

13.
A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (1O2) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.  相似文献   

14.
In recent decades, collagen is one of the most versatile biomaterials used in biomedical applications, mostly due to its biomimetic and structural composition in the extracellular matrix (ECM). Several attempts are proposed for designing innovative collagen‐based biomaterials and applying them in tissue regeneration. The regeneration of different tissues is prompted by different types and diverse physical forms of collagen‐based biomaterials prepared by various methods. Based on such concepts, the source, structure, and classification of collagen are briefly introduced in this review. Here, the commonly used physical forms and modification methods of collagen‐based biomaterials are reviewed, including hydrogels, scaffolds, and microspheres, followed by their applications in the regeneration of tissues and organs. Important proof‐of‐concept examples are described to demonstrate the outcomes on material characteristics, cellular reactions, and tissue regeneration. A concise assessment of the limitations that still exist and the developing trends in the future of collagen‐based biomaterials are put forward.  相似文献   

15.
The tumor growth and metastasis is the leading reason for the high mortality of breast cancer. Herein, it is first reported a deep tumor‐penetrating photothermal nanotherapeutics loading a near‐infrared (NIR) probe for potential photothermal therapy (PTT) of tumor growth and metastasis of breast cancer. The NIR probe of 1,1‐dioctadecyl‐3,3,3,3‐tetramethylindotricarbocyanine iodide (DiR), a lipophilicfluorescent carbocyanine dye with strong light‐absorbing capability, is entrapped into the photothermal nanotherapeutics for PTT application. The DiR‐loaded photothermal nanotherapeutics (DPN) is homogeneous nanometer‐sized particles with the mean diameter of 24.5 ± 4.1 nm. Upon 808 nm laser irradiation, DPN presents superior production of thermal energy than free DiR both in vitro and in vivo. The cell proliferation and migration activities of metastatic 4T1 breast cancer cells are obviously inhibited by DPN in combination with NIR irradiation. Moreover, DPN can induce a higher accumulation in tumor and penetrate into the deep interior of tumor tissues. The in vivo PTT measurements indicate that the growth and metastasis of breast cancer are entirely inhibited by a single treatment of DPN with NIR irradiation. Therefore, the deep tumor‐penetrating DPN can provide a promising strategy for PTT of tumor progression and metastasis of breast cancer.  相似文献   

16.
Near‐infrared (NIR)‐absorbing metal‐based nanomaterials have shown tremendous potential for cancer therapy, given their facile and controllable synthesis, efficient photothermal conversion, capability of spatiotemporal‐controlled drug delivery, and intrinsic imaging function. Tantalum (Ta) is among the most biocompatible metals and arouses negligible adverse biological responses in either oxidized or reduced forms, and thus Ta‐derived nanomaterials represent promising candidates for biomedical applications. However, Ta‐based nanomaterials by themselves have not been explored for NIR‐mediated photothermal ablation therapy. In this work, an innovative Ta‐based multifunctional nanoplatform composed of biocompatible tantalum sulfide (TaS2) nanosheets (NSs) is reported for simultaneous NIR hyperthermia, drug delivery, and computed tomography (CT) imaging. The TaS2 NSs exhibit multiple unique features including (i) efficient NIR light‐to‐heat conversion with a high photothermal conversion efficiency of 39%, (ii) high drug loading (177% by weight), (iii) controlled drug release triggered by NIR light and moderate acidic pH, (iv) high tumor accumulation via heat‐enhanced tumor vascular permeability, (v) complete tumor ablation and negligible side effects, and (vi) comparable CT imaging contrast efficiency to the widely clinically used agent iobitridol. It is expected that this multifunctional NS platform can serve as a promising candidate for imaging‐guided cancer therapy and selection of cancer patients with high tumor accumulation.  相似文献   

17.
Recently, near‐infrared (NIR) absorbing conjugated polymeric nanoparticles have received significant attention in photothermal therapy of cancer. Herein, polypyrrole (PPy), a NIR‐absorbing conjugate polymer, is used to coat ultra‐small iron oxide nanoparticles (IONPs), obtaining multifunctional IONP@PPy nanocomposite which is further modified by the biocompatible polyethylene glycol (PEG) through a layer‐by‐layer method to acquire high stability in physiological solutions. Utilizing the optical and magnetic properties of the yielded IONP@PPy‐PEG nanoparticles, in vivo magnetic resonance (MR) and photoacoustic imaging of tumor‐bearing mice are conducted, revealing strong tumor uptake of those nanoparticles after intravenous injection. In vivo photothermal therapy is then designed and carried out, achieving excellent tumor ablation therapeutic effect in mice experiments. These results promise the use of multifunctional NIR‐absorbing organic‐inorganic hybrid nanomaterials, such as IONP@PPy‐PEG presented here, for potential applications in cancer theranostics.  相似文献   

18.
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   

19.
Tellurium (Te) is an important semiconductor material with low band‐gap energy, which has attracted considerable attention in recent years, due to its special chemical and physical properties and wide potential in electrochemistry, optoelectronics, and biological fields. This study demonstrates a facile and high‐yield synthesis strategy of Te nanorods (PTW‐TeNRs) decorated by polysaccharide–protein complex, which can achieve simultaneous chemo‐photothermal combination therapy against cancers. PTW‐TeNRs alone possess high stability under physiological conditions, potent anticancer activities through induction of reactive oxygen species overproduction, and high selectivity among tumor and normal cells. More importantly, they exhibit strong near‐infrared (NIR) absorbance and good photothermal conversion ability from NIR light to heat energy. Furthermore, in combination with NIR laser irradiation, PTW‐TeNRs exhibit excellent chemo‐photothermal efficiency and low toxicity as evidenced by highly efficient tumor ablation ability, but show no obvious histological damage to the major organs. Taken together, this study provides a valid tactic for facile synthesis of multifunctional tellurium nanorods for efficient and combinational cancer therapy.  相似文献   

20.
Telluride molybdenum (MoTe2) nanosheets with wide near‐infrared (NIR) absorbance are functionalized with polyethylene glycol‐cyclic arginine‐glycine‐aspartic acid tripeptide (PEG‐cRGD). After loading a chemotherapeutic drug (doxorubicin, DOX), MoTe2‐PEG‐cRGD/DOX is used for combined photothermal therapy and chemotherapy. With the high photothermal conversion efficiency, MoTe2‐PEG‐cRGD/DOX exhibits favorable cells killing ability under NIR irradiation. Owing to the cRGD‐mediated specific tumor targeting, MoTe2‐PEG‐cRGD/DOX shows efficient accumulation in tumors to induce a strong tumor ablation effect. MoTe2‐PEG‐cRGD nanosheets, which are relatively stable in the circulation, could be degraded under NIR ray. The in vitro and in vivo experimental results demonstrate that this theranostic nanoagent, which could accumulate in tumors to allow photothermal imaging and combined therapy, is readily degradable in normal organs to enable rapid excretion and avoid long‐term retention/toxicity, holding great potential to treat tumor effectively.  相似文献   

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