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1.
Bioact Mater ; 35: 1-16, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38298451

RESUMO

Segmental bone defects, stemming from trauma, infection, and tumors, pose formidable clinical challenges. Traditional bone repair materials, such as autologous and allogeneic bone grafts, grapple with limitations including source scarcity and immune rejection risks. The advent of nucleic acid nanotechnology, particularly the use of DNA hydrogels in tissue engineering, presents a promising solution, attributed to their biocompatibility, biodegradability, and programmability. However, these hydrogels, typically hindered by high gelation temperatures (∼46 °C) and high construction costs, limit cell encapsulation and broader application. Our research introduces a novel polymer-modified DNA hydrogel, developed using nucleic acid nanotechnology, which gels at a more biocompatible temperature of 37 °C and is cost-effective. This hydrogel then incorporates tetrahedral Framework Nucleic Acid (tFNA) to enhance osteogenic mineralization. Furthermore, considering the modifiability of tFNA, we modified its chains with Aptamer02 (Apt02), an aptamer known to foster angiogenesis. This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells (BMSCs) and angiogenesis in human umbilical vein endothelial cells (HUVECs), with cell sequencing confirming their targeting efficacy, respectively. In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation. This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction, marking a significant advancement in tissue engineering and regenerative medicine.

2.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38399465

RESUMO

Hydroxyapatite (HAP) has garnered considerable interest in biomedical engineering for its diverse applications. Yet, the synthesis of HAP integrated with functional natural organic components remains an area ripe for exploration. This study innovatively utilizes the versatile properties of tea polyphenol (TP) to synthesize HAP nanomaterials with superior crystallinity and distinct morphologies, notably rod-like structures, via a chemical deposition process in a nitrogen atmosphere. This method ensures an enhanced integration of TP, as confirmed by thermogravimetric (TGA) analysis and a variety of microscopy techniques, which also reveal the dependence of TP content and crystallinity on the synthesis method employed. The research significantly impacts the field by demonstrating how synthesis conditions can alter material properties. It leads the way in employing TP-modified nano-HAP particles for biomedical applications. The findings of this study are crucial as they open avenues for the future development of tailored HAP nanomaterials, aiming at specific medical applications and advancements in nanotechnology.

3.
Mater Horiz ; 11(6): 1465-1483, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38221872

RESUMO

Osteoarthritis (OA) is a common joint disease known for cartilage degeneration, leading to a substantial burden on individuals and society due to its high disability rate. However, current clinical treatments for cartilage defects remain unsatisfactory due to the unclear mechanisms underlying cartilage regeneration. Tissue engineering hydrogels have emerged as an attractive approach in cartilage repair. Recent research studies have indicated that stem cells can sense the mechanical strength of hydrogels, thereby regulating their differentiation fate. In this study, we present the groundbreaking construction of dual-network DNA-silk fibroin (SF) hydrogels with controllable surface rigidity. The supramolecular networks, formed through DNA base-pairing, induce the development of ß-sheet structures by constraining and aggregating SF molecules. Subsequently, SF was cross-linked via horseradish peroxidase (HRP)-mediated enzyme reactions to form the second network. Experimental results demonstrated a positive correlation between the surface rigidity of dual-network DNA-SF hydrogels and the DNA content. Interestingly, it was observed that dual-network DNA-SF hydrogels with moderate surface rigidity exhibited the highest effectiveness in facilitating the migration of bone marrow mesenchymal stem cells (BMSCs) and their chondrogenic differentiation. Transcriptome sequencing further confirmed that dual-network DNA-SF hydrogels primarily enhanced chondrogenic differentiation of BMSCs by upregulating the Wnt and TGF-ß signaling pathways while accelerating collagen II synthesis. Furthermore, in vivo studies revealed that dual-network DNA-SF hydrogels with moderate surface rigidity significantly accelerated cartilage regeneration. In summary, the dual-network DNA-SF hydrogels represent a promising and novel therapeutic strategy for cartilage regeneration.


Assuntos
Doenças das Cartilagens , Fibroínas , Humanos , Fibroínas/química , Hidrogéis , Cartilagem/fisiologia , Engenharia Tecidual/métodos , Diferenciação Celular/genética
4.
Front Bioeng Biotechnol ; 9: 820468, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35087811

RESUMO

Reactive oxygen species (ROS) are the key signaling molecules in many physiological signs of progress and are associated with almost all diseases, such as atherosclerosis, aging, and cancer. Bone is a specific connective tissue consisting of cells, fibers, and mineralized extracellular components, and its quality changes with aging and disease. Growing evidence indicated that overproduced ROS accumulation may disrupt cellular homeostasis in the progress of bone modeling and remodeling, leading to bone metabolic disease. Thus, ROS-responsive biomaterials have attracted great interest from many researchers as promising strategies to realize drug release or targeted therapy for bone-related diseases. Herein, we endeavor to introduce the role of ROS in the bone microenvironment, summarize the mechanism and development of ROS-responsive biomaterials, and their completion and potential for future therapy of bone-related diseases.

5.
Biomater Sci ; 8(19): 5390-5401, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32996951

RESUMO

Targeted delivery of anticancer drugs is one of the most promising methods for cancer therapy. However, barriers including complicated procedures, costly preparation, and toxic side effects have restricted the development of nuclear-targeted nanocarriers. Natural polysaccharides as extracellular matrix constituents or analogs play an important role in biomineralization. Herein, a simple, polysaccharide-intervened preparation of hydroxyapatite (HA) hybrid nanoparticles (NPs) with low crystallinity was used as a bio-safe carrier for targeting the delivery of doxorubicin (DOX) for efficient anticancer therapy. The poorly crystallized hybrid HA NPs were specifically taken up by cancer cells (HeLa cells), and subsequently, the abrupt degradation of HA nanoparticles would cause a change in the osmotic pressure, leading to the explosive death of cancer cells. Furthermore, the hybrid HA NPs were size changeable and capable of directly delivering the anti-cancer drug into the nucleus of cancer cells, thereby efficiently killing cancer cells. In addition, the HA/ALG NPs reduce the toxicity of DOX to L929 cells and cause little negative effect on normal tissue cells. The in vitro and in vivo experiments confirmed that the size-changeable HA-ALG/DOX could be a promising nuclear-targeted delivery nanocarrier for efficient cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Doxorrubicina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Durapatita/uso terapêutico , Células HeLa , Humanos , Ácido Hialurônico/uso terapêutico , Neoplasias/tratamento farmacológico , Polissacarídeos/uso terapêutico
6.
ACS Appl Mater Interfaces ; 12(31): 34610-34619, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32633488

RESUMO

Photothermal nanoparticles locally release heat when irradiated by near-infrared (NIR). Clinical applications initially involved tumor treatment, but currently extend toward bacterial infection control. Applications toward much smaller, micrometer-sized bacterial infections, however, bear the risk of collateral damage by dissipating heat into tissues surrounding an infection site. This can become a complication when photothermal nanoparticle coatings are clinically applied on biomaterial surfaces requiring tissue integration, such as titanium-made, bone-anchored dental implants. Dental implants can fail due to infection in the pocket formed between the implant screw and the surrounding soft tissue ("peri-implantitis"). We address the hitherto neglected potential complication of collateral tissue damage by evaluating photothermal, polydopamine nanoparticle (PDA-NP) coatings on titanium surfaces in different coculture models. NIR irradiation of PDA-NP-coated (200 µg/cm2) titanium surfaces with adhering Staphylococcus aureus killed staphylococci within an irradiation time window of around 3 min. Alternatively, when covered with human gingival fibroblasts, this irradiation time window maintained surface coverage by fibroblasts. Contaminating staphylococci on PDA-NP-coated titanium surfaces, as can be per-operatively introduced, reduced surface coverage by fibroblasts, and this could be prevented by NIR irradiation for 5 min or longer prior to allowing fibroblasts to adhere and grow. Negative impacts of early postoperative staphylococcal challenges to an existing fibroblast layer covering a coated surface were maximally prevented by 3 min NIR irradiation. Longer irradiation times caused collateral fibroblast damage. Late postoperative staphylococcal challenges to a protective keratinocyte layer covering a fibroblast layer required 10 min NIR irradiation for adverting a staphylococcal challenge. This is longer than foreseen from monoculture studies because of additional heat uptake by the keratinocyte layer. Summarizing, photothermal treatment of biomaterial-associated infection requires precise timing of NIR irradiation to prevent collateral damage to tissues surrounding the infection site.


Assuntos
Antibacterianos/farmacologia , Indóis/farmacologia , Nanopartículas/química , Polímeros/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Temperatura , Titânio/farmacologia , Antibacterianos/química , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/microbiologia , Humanos , Indóis/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Processos Fotoquímicos , Polímeros/química , Propriedades de Superfície , Titânio/química
7.
Nanoscale ; 10(25): 12109-12122, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29915821

RESUMO

The development of safe and effective nano-drug delivery systems to deliver anticancer drugs to targeted cells and organs is crucial to enhance the therapeutic efficacy and overcome unwanted side effects of chemotherapy. Herein, we prepared CD44-targeted dual-stimuli responsive human hair keratin and hyaluronic acid nanogels (KHA-NGs) through a simple crosslinking method. KHA-NGs, which consisted of spheres 50 nm in diameter, were used as carriers to load the anticancer drug doxorubicin hydrochloride (DOX). The drug release, cellular uptake, cytotoxicity, and targeting ability of DOX-loaded KHA-NGs (DOX@KHA-NGs) were assessed in vitro and the anticancer effects were further evaluated in vivo. The DOX@KHA-NGs had a super-high drug loading capacity (54.1%, w/w) and were stable under physiological conditions (10 µM glutathione (GSH)), with the drug being rapidly released under a tumor cell microenvironment of trypsin and 10 mM GSH. Cellular uptake and in vitro cytotoxicity results indicated that DOX@KHA-NGs specifically targeted cancer cells and effectively inhibited their growth. Furthermore, KHA-NGs were capable of improving intracellular nitric oxide levels, which sensitizes the cells and enhances the anticancer efficacy of chemotherapeutic drugs. In vivo experiments showed that DOX@KHA-NGs had a better anti-tumor effect and lower side effects compared to free DOX. These results suggest that the bio-responsive KHA-NGs have potential applications for targeted cancer therapy.


Assuntos
Portadores de Fármacos/química , Ácido Hialurônico/química , Queratinas/química , Nanopartículas/química , Neoplasias Experimentais/tratamento farmacológico , Óxido Nítrico/química , Animais , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Feminino , Géis/química , Humanos , Melanoma Experimental , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Microambiente Tumoral
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