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1.
Stem Cell Res Ther ; 15(1): 135, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715130

RESUMO

BACKGROUND: Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects. METHODS: The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane's potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining. RESULTS: The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone. CONCLUSIONS: The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering.


Assuntos
Regeneração Óssea , Regeneração Óssea/efeitos dos fármacos , Animais , Osteogênese/efeitos dos fármacos , Engenharia Tecidual/métodos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Camundongos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Membranas Artificiais , Regeneração Tecidual Guiada/métodos , Alicerces Teciduais/química , Poliésteres/química , Poliésteres/farmacologia , Ratos
2.
J Nanobiotechnology ; 22(1): 244, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735969

RESUMO

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.


Assuntos
Macrófagos , Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Poliuretanos , Ratos Sprague-Dawley , Células de Schwann , Animais , Regeneração Nervosa/efeitos dos fármacos , Poliuretanos/química , Ratos , Macrófagos/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Nanofibras/química , Nervo Isquiático/efeitos dos fármacos , Regeneração Tecidual Guiada/métodos , Masculino , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Alicerces Teciduais/química , Camundongos , Células RAW 264.7
3.
Front Immunol ; 15: 1396486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694497

RESUMO

Bone marrow failure (BMF) has become one of the most studied autoimmune disorders, particularly due to its prevalence both as an inherited disease, but also as a result of chemotherapies. BMF is associated with severe symptoms such as bleeding episodes and susceptibility to infections, and often has underlying characteristics, such as anemia, thrombocytopenia, and neutropenia. The current treatment landscape for BMF requires stem cell transplantation or chemotherapies to induce immune suppression. However, there is limited donor cell availability or dose related toxicity associated with these treatments. Optimizing these treatments has become a necessity. Polymer-based materials have become increasingly popular, as current research efforts are focused on synthesizing novel cell matrices for stem cell expansion to solve limited donor cell availability, as well as applying polymer delivery vehicles to intracellularly deliver cargo that can aid in immunosuppression. Here, we discuss the importance and impact of polymer materials to enhance therapeutics in the context of BMF.


Assuntos
Polímeros , Humanos , Polímeros/química , Animais , Doenças da Medula Óssea/induzido quimicamente , Doenças da Medula Óssea/terapia , Transtornos da Insuficiência da Medula Óssea/terapia , Materiais Biocompatíveis
4.
Adv Tech Stand Neurosurg ; 49: 307-326, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38700690

RESUMO

Cranial repair in children deserves particular attention since many issues are still controversial. Furthermore, literature data offer a confused picture of outcome of cranioplasty, in terms of results and complication rates, with studies showing inadequate follow-up and including populations that are not homogeneous by age of the patients, etiology, and size of the bone defect.Indeed, age has merged in the last years as a risk factor for resorption of autologous bone flap that is still the most frequent complication in cranial repair after decompressive craniectomy.Age-related factors play a role also when alloplastic materials are used. In fact, the implantation of alloplastic materials is limited by skull growth under 7 years of age and is contraindicated in the first years if life. Thus, the absence of an ideal material for cranioplasty is even more evident in children with a steady risk of complications through the entire life of the patient that is usually much longer than surgical follow-up.As a result, specific techniques should be adopted according to the age of the patient and etiology of the defect, aiming to repair the skull and respect its residual growth.Thus, autologous bone still represents the best option for cranial repair, though limitations exist. As an alternative, biomimetic materials should ideally warrant the possibility to overcome the limits of other inert alloplastic materials by favoring osteointegration or osteoinduction or both.On these grounds, this paper aims to offer a thorough overview of techniques, materials, and peculiar issues of cranial repair in children.


Assuntos
Crânio , Humanos , Criança , Crânio/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Transplante Ósseo/métodos , Craniectomia Descompressiva/métodos , Materiais Biocompatíveis
5.
ACS Nano ; 18(19): 12210-12224, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38695533

RESUMO

Accurate postoperative assessment of varying mechanical properties is crucial for customizing patient-specific treatments and optimizing rehabilitation strategies following Achilles tendon (AT) rupture and reconstruction surgery. This study introduces a wireless, chip-less, and immune-tolerant in vivo strain-sensing suture designed to continuously monitor mechanical stiffness variations in the reconstructed AT throughout the healing process. This innovative sensing suture integrates a standard medical suturing thread with a wireless fiber strain-sensing system, which incorporates a fiber strain sensor and a double-layered inductive coil for wireless readout. The winding design of Au nanoparticle-based fiber electrodes and a hollow core contribute to the fiber strain sensor's high sensitivity (factor of 6.2 and 15.1 pF for revised sensitivity), negligible hysteresis, and durability over 10,000 stretching cycles. To ensure biocompatibility and immune tolerance during extended in vivo periods, an antibiofouling lubricant layer was applied to the sensing suture. Using this sensing system, we successfully monitored the strain responses of the reconstructed AT in an in vivo porcine model. This facilitated the postoperative assessment of mechanical stiffness variations through a well-established analytical model during the healing period.


Assuntos
Materiais Biocompatíveis , Suturas , Tecnologia sem Fio , Tecnologia sem Fio/instrumentação , Animais , Suínos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Tendão do Calcâneo , Ouro/química , Nanopartículas Metálicas/química
6.
ACS Nano ; 18(19): 12341-12354, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38695772

RESUMO

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.


Assuntos
Nanofibras , Animais , Ratos , Nanofibras/química , Cicatrização/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Aderências Teciduais/prevenção & controle , Ratos Sprague-Dawley , Adesão Celular/efeitos dos fármacos , Cério/química , Cério/farmacologia , Propriedades de Superfície , Camundongos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia
7.
ACS Nano ; 18(19): 12477-12488, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38699877

RESUMO

Progress in the design and synthesis of nanostructured self-assembling systems has facilitated the realization of numerous nanoscale geometries, including fibers, ribbons, and sheets. A key challenge has been achieving control across multiple length scales and creating macroscopic structures with nanoscale organization. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical macrostructures. Further, we demonstrate the ability to tune the nanostructure of macroscopic hydrogels through modulating phosphate buffer concentration during peptide self-assembly. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an extracellular matrix-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to decouple nanostructure from macrostructure and generate a gradient of anisotropic nanofibrous hydrogels. We anticipate that control of architecture at multiple length scales will be critical for a variety of applications, including the bottom-up tissue engineering explored here.


Assuntos
Hidrogéis , Nanofibras , Peptídeos , Nanofibras/química , Peptídeos/química , Hidrogéis/química , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Anisotropia , Animais
8.
Carbohydr Polym ; 338: 122204, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763712

RESUMO

This study presents the development and characterization of a novel double-network self-healing hydrogel based on N-carboxyethyl chitosan (CEC) and oxidized dextran (OD) with the incorporation of crosslinked collagen (CEC-OD/COL-GP) to enhance its biological and physicochemical properties. The hydrogel formed via dynamic imine bond formation exhibited efficient self-healing within 30 min, and a compressive modulus recovery of 92 % within 2 h. In addition to its self-healing ability, CEC-OD/COL-GP possesses unique physicochemical characteristics including transparency, injectability, and adhesiveness to various substrates and tissues. Cell encapsulation studies confirmed the biocompatibility and suitability of the hydrogel as a cell-culture scaffold, with the presence of a collagen network that enhances cell adhesion, spreading, long-term cell viability, and proliferation. Leveraging their unique properties, we engineered assemblies of self-healing hydrogel modules for controlled spatiotemporal drug delivery and constructed co-culture models that simulate angiogenesis in tumor microenvironments. Overall, the CEC-OD/COL-GP hydrogel is a versatile and promising material for biomedical applications, offering a bottom-up approach for constructing complex structures with self-healing capabilities, controlled drug release, and support for diverse cell types in 3D environments. This hydrogel platform has considerable potential for advancements in tissue engineering and therapeutic interventions.


Assuntos
Adesão Celular , Quitosana , Dextranos , Hidrogéis , Hidrogéis/química , Hidrogéis/farmacologia , Quitosana/química , Dextranos/química , Humanos , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno/química , Animais , Liberação Controlada de Fármacos , Proliferação de Células/efeitos dos fármacos , Encapsulamento de Células/métodos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Camundongos , Biomimética/métodos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Alicerces Teciduais/química
9.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731871

RESUMO

Implanted medical devices are widely used across various medical specialties for numerous applications, ranging from cardiovascular supports to orthopedic prostheses and cosmetic enhancements. However, recent observations have raised concerns about the potential of these implants to induce malignancies in the tissues surrounding them. There have been several case reports documenting the occurrence of cancers adjacent to these devices, prompting a closer examination of their safety. This review delves into the epidemiology, clinical presentations, pathological findings, and hypothesized mechanisms of carcinogenesis related to implanted devices. It also explores how the surgical domain and the intrinsic properties and biocompatibility of the implants might influence the development of these rare but serious malignancies. Understanding these associations is crucial for assessing the risks associated with the use of medical implants, and for developing strategies to mitigate potential adverse outcomes.


Assuntos
Materiais Biocompatíveis , Neoplasias , Próteses e Implantes , Humanos , Materiais Biocompatíveis/efeitos adversos , Próteses e Implantes/efeitos adversos , Neoplasias/etiologia , Animais
10.
J Nanobiotechnology ; 22(1): 217, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725012

RESUMO

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.


Assuntos
Antioxidantes , Bandagens , Quitosana , Hidrogéis , Plasma Rico em Plaquetas , Povidona , Cicatrização , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Cicatrização/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Povidona/química , Povidona/análogos & derivados , Hidrogéis/química , Hidrogéis/farmacologia , Plasma Rico em Plaquetas/química , Animais , Camundongos , Masculino , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Humanos
11.
ACS Appl Mater Interfaces ; 16(19): 24248-24260, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38693878

RESUMO

Biomedical devices are vulnerable to infections and biofilm formation, leading to extended hospital stays, high expenditure, and increased mortality. Infections are clinically treated via the administration of systemic antibiotics, leading to the development of antibiotic resistance. A multimechanistic strategy is needed to design an effective biomaterial with broad-spectrum antibacterial potential. Recent approaches have investigated the fabrication of innately antimicrobial biomedical device surfaces in the hope of making the antibiotic treatment obsolete. Herein, we report a novel fabrication strategy combining antibacterial nitric oxide (NO) with an antibiofilm agent N-acetyl cysteine (NAC) on a polyvinyl chloride surface using polycationic polyethylenimine (PEI) as a linker. The designed biomaterial could release NO for at least 7 days with minimal NO donor leaching under physiological conditions. The proposed surface technology significantly reduced the viability of Gram-negative Escherichia coli (>97%) and Gram-positive Staphylococcus aureus (>99%) bacteria in both adhered and planktonic forms in a 24 h antibacterial assay. The composites also exhibited a significant reduction in biomass and extra polymeric substance accumulation in a dynamic environment over 72 h. Overall, these results indicate that the proposed combination of the NO donor with mucolytic NAC on a polymer surface efficiently resists microbial adhesion and can be used to prevent device-associated biofilm formation.


Assuntos
Acetilcisteína , Antibacterianos , Biofilmes , Escherichia coli , Óxido Nítrico , Staphylococcus aureus , Acetilcisteína/química , Acetilcisteína/farmacologia , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Polietilenoimina/química , Polietilenoimina/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Testes de Sensibilidade Microbiana , Cloreto de Polivinila/química , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia
12.
ACS Appl Mater Interfaces ; 16(19): 24261-24273, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38709741

RESUMO

In this work, bioactive glass (BG) particles obtained by three different methods (melt-quenching, sol-gel, and sol-gel-EISA) were used as modifiers of polyphenol-loaded PCL-based composites. The composites were loaded with polyphenolic compounds (PPh) extracted from sage (Salvia officinalis L.). It was hypothesized that BG particles, due to their different textural properties (porosity, surface area) and surface chemistry (content of silanol groups), would act as an agent to control the release of polyphenols from PCL/BG composite films and other significant properties associated with and affected by the presence of PPh. The polyphenols improved the hydrophilicity, apatite-forming ability, and mechanical properties of the composites and provided antioxidant and anticancer activity. As the BG particles had different polyphenol-binding capacities, they modulated the kinetics of polyphenol release from the composites and the aforementioned properties to a great extent. Importantly, the PPh-loaded materials exhibited multifaceted and selective anticancer activity, including ROS-mediated cell cycle arrest and apoptosis of osteosarcoma (OS) cells (Saos-2) via Cdk2-, GADD45G-, and caspase-3/7-dependent pathways. The materials showed a cytotoxic and antiproliferative effect on cancerous osteoblasts but not on normal human osteoblasts. These results suggest that the composites have great potential as biomaterials for treating bone defects, particularly following surgical removal of OS tumors.


Assuntos
Antineoplásicos , Vidro , Polifenóis , Polifenóis/química , Polifenóis/farmacologia , Humanos , Vidro/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Poliésteres/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia
13.
Biomed Mater ; 19(4)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38729172

RESUMO

The sensitivity and diagnostic accuracy of magnetic resonance imaging mainly depend on the relaxation capacity of contrast agents (CAs) and their accumulated amount at the pathological region. Due to the better biocompatibility and high-spin capacity, Fe-complexes have been studied widely as an alternative to replace popular Gd-based CAs associated with potential biotoxicity. Compared with a variety of Fe complex-based CAs, such as small molecular, macrocyclic, multinuclear complexes, the form of nanoparticle exhibits outstanding longitudinal relaxation, but the clinical transformation was still limited by the inconspicuous difference of contrast between tumor and normal tissue. The enhanced effect of contrast is a positive relation as relaxation of CAs and their concentration in desired region. To specifically improve the amount of CAs accumulated in the tumor, pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) was modified on melanin, a ubiquitous natural pigment providing much active sites for chelating with Fe(III). The Fe(III)-Mel-PEOz we prepared could raise the tumor cell endocytosis efficiency via switching surface charge from anion to cation with the stimuli of the decreasing pH of tumor microenvironment. The change of pH has negligible effect on ther1of Fe(III)-Mel-PEOz, which is always maintained at around 1.0 mM-1s-1at 0.5 T. Moreover, Fe(III)-Mel-PEOz exhibited low cytotoxicity, and satisfactory enhancement of positive contrast effectin vivo. The excellent biocompatibility and stable relaxation demonstrate the high potential of Fe(III)-Mel-PEOz in the diagnosis of tumor.


Assuntos
Materiais Biocompatíveis , Meios de Contraste , Ferro , Imageamento por Ressonância Magnética , Melaninas , Melaninas/química , Concentração de Íons de Hidrogênio , Imageamento por Ressonância Magnética/métodos , Meios de Contraste/química , Animais , Materiais Biocompatíveis/química , Humanos , Ferro/química , Camundongos , Linhagem Celular Tumoral , Poliaminas/química , Nanopartículas/química , Microambiente Tumoral
14.
Invest Ophthalmol Vis Sci ; 65(5): 24, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38748430

RESUMO

Purpose: Hydrogels derived from decellularized tissues are promising biomaterials in tissue engineering, but their rapid biodegradation can hinder in vitro cultivation. This study aimed to retard biodegradation of a hydrogel derived from porcine decellularized lacrimal glands (dLG-HG) by crosslinking with genipin to increase the mechanical stability without affecting the function and viability of lacrimal gland (LG)-associated cells. Methods: The effect of different genipin concentrations on dLG-HG stiffness was measured rheologically. Cell-dependent biodegradation was quantified over 10 days, and the impact on matrix metalloproteinase (MMP) activity was quantified by gelatin and collagen zymography. The viability of LG epithelial cells (EpCs), mesenchymal stem cells (MSCs), and endothelial cells (ECs) cultured on genipin-crosslinked dLG-HG was assessed after 10 days, and EpC secretory activity was analyzed by ß-hexosaminidase assay. Results: The 0.5-mM genipin increased the stiffness of dLG-HG by about 46%, and concentrations > 0.25 mM caused delayed cell-dependent biodegradation and reduced MMP activity. The viability of EpCs, MSCs, and ECs was not affected by genipin concentrations of up to 0.5 mM after 10 days. Moreover, up to 0.5-mM genipin did not negatively affect EpC secretory activity compared to control groups. Conclusions: A concentration of 0.5-mM genipin increased dLG-HG stiffness, and 0.25-mM genipin was sufficient to prevent MMP-dependent degradation. Importantly, concentrations of up to 0.5-mM genipin did not compromise the viability of LG-associated cells or the secretory activity of EpCs. Thus, crosslinking with genipin improves the properties of dLG-HG for use as a substrate in LG tissue engineering.


Assuntos
Sobrevivência Celular , Reagentes de Ligações Cruzadas , Hidrogéis , Iridoides , Engenharia Tecidual , Animais , Iridoides/farmacologia , Iridoides/metabolismo , Suínos , Engenharia Tecidual/métodos , Reagentes de Ligações Cruzadas/farmacologia , Células Cultivadas , Células-Tronco Mesenquimais/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Materiais Biocompatíveis
15.
Sci Adv ; 10(20): eadl0479, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38748805

RESUMO

Reactive oxygen species (ROS) play an important role in regulating the immune system by affecting pathogens, cancer cells, and immune cells. Recent advances in biomaterials have leveraged this mechanism to precisely modulate ROS levels in target tissues for improving the effectiveness of immunotherapies in infectious diseases, cancer, and autoimmune diseases. Moreover, ROS-responsive biomaterials can trigger the release of immunotherapeutics and provide tunable release kinetics, which can further boost their efficacy. This review will discuss the latest biomaterial-based approaches for both precise modulation of ROS levels and using ROS as a stimulus to control the release kinetics of immunotherapeutics. Finally, we will discuss the existing challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches for immunotherapy, and provide an outlook for future research.


Assuntos
Imunoterapia , Espécies Reativas de Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Imunoterapia/métodos , Animais , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/metabolismo , Materiais Biocompatíveis/química
16.
J Nanobiotechnology ; 22(1): 250, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750519

RESUMO

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.


Assuntos
Regeneração Óssea , Fosfatos de Cálcio , Osteogênese , Osteossarcoma , Alicerces Teciduais , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Animais , Regeneração Óssea/efeitos dos fármacos , Alicerces Teciduais/química , Coelhos , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Osteogênese/efeitos dos fármacos , Poliésteres/química , Humanos , Diferenciação Celular/efeitos dos fármacos , Neoplasias Ósseas/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Células de Schwann/efeitos dos fármacos , Nanofibras/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Selênio/química , Selênio/farmacologia
17.
ACS Appl Bio Mater ; 7(5): 3316-3329, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38691017

RESUMO

Basic fibroblast growth factor (bFGF) plays an important role in active wound repair. However, the existing dosage forms in clinical applications are mainly sprays and freeze-dried powders, which are prone to inactivation and cannot achieve a controlled release. In this study, a bioactive wound dressing named bFGF-ATP-Zn/polycaprolactone (PCL) nanodressing with a "core-shell" structure was fabricated by emulsion electrospinning, enabling the sustained release of bFGF. Based on the coordination and electrostatic interactions among bFGF, ATP, and Zn2+, as well as their synergistic effect on promoting wound healing, a bFGF-ATP-Zn ternary combination system was prepared with higher cell proliferation activity and used as the water phase for emulsion electrospinning. The bFGF-ATP-Zn/PCL nanodressing demonstrated improved mechanical properties, sustained release of bFGF, cytocompatibility, and hemocompatibility. It increased the proliferation activity of human dermal fibroblasts (HDFs) and enhanced collagen secretion by 1.39 and 3.45 times, respectively, while reducing the hemolysis rate to 3.13%. The application of the bFGF-ATP-Zn/PCL nanodressing in mouse full-thickness skin defect repair showed its ability to accelerate wound healing and reduce wound scarring within 14 days. These results provide a research basis for the development and application of this bioactive wound dressing product.


Assuntos
Trifosfato de Adenosina , Materiais Biocompatíveis , Proliferação de Células , Emulsões , Fator 2 de Crescimento de Fibroblastos , Teste de Materiais , Cicatrização , Zinco , Cicatrização/efeitos dos fármacos , Emulsões/química , Animais , Zinco/química , Zinco/farmacologia , Humanos , Fator 2 de Crescimento de Fibroblastos/química , Fator 2 de Crescimento de Fibroblastos/farmacologia , Camundongos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Tamanho da Partícula , Fibroblastos/efeitos dos fármacos , Poliésteres/química , Poliésteres/farmacologia , Bandagens
18.
ACS Appl Bio Mater ; 7(5): 3375-3387, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38693867

RESUMO

Encapsulation of natural polymer pectin (Pec) into a zeolitic imidazolate framework-12 (ZIF-12) matrix via a simple chemical method toward anticancer agent gallic acid (GA) detection is reported in this work. GA, a natural phenol found in many food sources, has gained attention by its biological effects on the human body, such as an antioxidant and anti-inflammatory. Therefore, it is crucial to accurately and rapidly determine the GA level in humans. The encapsulation of Pec inside the ZIF-12 has been successfully confirmed from the physiochemical studies such as XRD, Raman, FTIR, and XPS spectroscopy along with morphological FESEM, BET, and HRTEM characterization. Under optimized conditions, the Pec@ZIF-12 composite exhibits wide linear range of 20 nM-250 µM with a detection limit of 2.2 nM; also, it showed excellent selectivity, stability, and reproducibility. Furthermore, the real sample analysis of food samples including tea, coffee, grape, and pomegranate samples shows exceptional recovery percentage in an unspiked manner. So far, there is little literature for encapsulating proteins, enzymes, metals, etc., that have been reported; here, we successfully encapsulated a natural polymer Pec inside the ZIF-12 cage. This encapsulation significantly enhanced the composite electrochemical performance, which could be seen from the overall results. All of these strongly suggest that the proposed Pec@ZIF-12 composite could be used for miniaturized device fabrication for the evaluation of GA in both home and industrial applications.


Assuntos
Antineoplásicos , Técnicas Eletroquímicas , Imidazóis , Zeolitas , Zeolitas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Imidazóis/química , Teste de Materiais , Ácido Gálico/química , Tamanho da Partícula , Materiais Biocompatíveis/química , Polímeros/química , Pectinas/química , Estruturas Metalorgânicas/química , Humanos
19.
ACS Appl Bio Mater ; 7(5): 3154-3163, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38695332

RESUMO

ß-Galactosidase (ß-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor ß-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine ß-Gala activity effectively. Via the sensing performance, the catalytic activity of ß-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-ß-d-galactopyranoside (KOßDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing ß-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of ß-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.


Assuntos
Neoplasias da Mama , Quempferóis , Teste de Materiais , Nanopartículas , Silício , beta-Galactosidase , Humanos , beta-Galactosidase/metabolismo , Silício/química , Células MCF-7 , Nanopartículas/química , Quempferóis/química , Quempferóis/farmacologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Tamanho da Partícula , Colorimetria , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Feminino , Estrutura Molecular
20.
ACS Appl Bio Mater ; 7(5): 3506-3514, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38696441

RESUMO

Horseradish peroxidase (HRP)-mediated hydrogelation, caused by the cross-linking of phenolic groups in polymers in the presence of hydrogen peroxide (H2O2), is an effective route for bioink solidification in 3D bioprinting. Sugar beet pectin (SBP) naturally has cross-linkable phenols through the enzymatic reaction. Therefore, chemical modifications are not required, unlike the various polymers that have been used in the enzymatic cross-linking system. In this study, we report the application of SBP in extrusion-based bioprinting including HRP-mediated bioink solidification. In this system, H2O2 necessary for the solidification of inks is supplied in the gas phase. Cell-laden liver lobule-like constructs could be fabricated using bioinks consisting of 10 U/mL HRP, 4.0 and 6.0 w/v% SBP, and 6.0 × 106 cells/mL human hepatoblastoma (HepG2) cells exposed to air containing 16 ppm of H2O2 concurrently during printing and 10 min postprinting. The HepG2 cells enclosed in the printed constructs maintained their viability, metabolic activity, and hepatic functions from day 1 to day 7 of the culture, which indicates the cytocompatibility of this system. Taken together, this result demonstrates the potential of SBP and HRP cross-linking systems for 3D bioprinting, which can be applied in tissue engineering applications.


Assuntos
Beta vulgaris , Materiais Biocompatíveis , Bioimpressão , Peroxidase do Rábano Silvestre , Teste de Materiais , Pectinas , Impressão Tridimensional , Peroxidase do Rábano Silvestre/metabolismo , Peroxidase do Rábano Silvestre/química , Beta vulgaris/química , Humanos , Pectinas/química , Células Hep G2 , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Peróxido de Hidrogênio/química , Tamanho da Partícula , Sobrevivência Celular/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/síntese química , Engenharia Tecidual
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