RESUMEN

In this study, multifunctional injectable mineralized antibacterial nanocomposite hydrogels were prepared by a homogenous distribution of high content of (up to 60 wt%) Sr-substituted hydroxyapatite (Sr-HAp) nanoparticles into covalently cross-linked ɛ-polylysine (ɛ-PL) and hyaluronic acid (HA) hydrogel network. The developed bone-targeted nanocomposite hydrogels were to synergistically combine the functional properties of bioactive Sr-HAp nanoparticles and antibacterial ɛ-PL-HA hydrogels for bone tissue regeneration. Viscoelasticity, injectability, structural parameters, degradation, antibacterial activity, and in vitro biocompatibility of the fabricated nanocomposite hydrogels were characterized. Physical performances of the ɛ-PL-HA hydrogels can be tailored by altering the mass ratio of Sr-HAp. The nanocomposite hydrogels revealed good stability against enzymatic degradation, which increased from 5 to 19 weeks with increasing the mass ratio of Sr-HAp from 40 % to 60 %. The loading of the Sr-HAp at relatively high mass ratios did not suppress the fast-acting and long-term antibacterial activity of the ɛ-PL-HA hydrogels against S. aureus and E. coli. The cell studies confirmed the cytocompatibility and pre-collagen I synthesis-promoting activity of the fabricated nanocomposite hydrogels.

RESUMEN

Chronic wound healing is a common clinical challenge, characterized by bacterial infection, protracted inflammatory response, oxidative stress, and insufficient neovascularization. Nanozymes have emerged as a promising solution for treating skin wounds due to their antioxidant, antibacterial, and angiogenic properties. In recent years, combining nanozymes with hydrogels to jointly promote wound healing has attracted increasing research interest. However, most of the current nanocomposite hydrogels are still not effective in simultaneously controlling inflammatory, oxidative stress and bacterial invasion in wound healing. Improving the therapeutic functional diversity and efficacy of nanocomposite hydrogels remains a problem that needs to be addressed. In this study, we prepared nanocomposite hydrogels (GelMD-Cur@ZHMCe) by combining methylacrylated gelatin modified with dopamine (GelMD) with Zinc-doped hollow mesoporous cerium oxide nanoparticles loaded with curcumin (Cur@ZHMCe). The resulting hydrogels exhibited excellent water absorption, adhesion, and biocompatibility. In vitro and in vivo studies have demonstrated that GelMD-Cur@ZHMCe has excellent antioxidant, antibacterial, anti-inflammatory and vasculature-promoting properties, which enable it to rapidly promote wound repair. The wound healing rate of the rat total skin defect infection model treated with GelMD-Cur@ZHMCe reached 98.5±4.9 % after 14 days of treatment. It was demonstrated that this multifunctional nanocomposite hydrogel provides a promising therapeutic strategy for skin repair.

Asunto(s)

Antibacterianos , Antioxidantes , Cerio , Curcumina , Dopamina , Gelatina , Hidrogeles , Nanocompuestos , Ratas Sprague-Dawley , Cicatrización de Heridas , Zinc , Hidrogeles/química , Hidrogeles/administración & dosificación , Cerio/química , Cerio/administración & dosificación , Cerio/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Gelatina/química , Curcumina/administración & dosificación , Curcumina/química , Curcumina/farmacología , Nanocompuestos/química , Nanocompuestos/administración & dosificación , Dopamina/química , Dopamina/administración & dosificación , Zinc/química , Zinc/administración & dosificación , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/química , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Antioxidantes/química , Masculino , Ratas , Ratones , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Piel/efectos de los fármacos , Piel/metabolismo , Humanos

RESUMEN

Traditional granular hydrogels showed excellent injectivity, thermal integrity, and efficient remediation of heterogeneous reservoirs. However, granular hydrogels have demonstrated their inability to adapt to fractures due to the lack of sufficient interactions. Herein, we present new nanocomposite hydrogels consisting of cationic nanogelators and anionic granular hydrogels that can chemically in situ reform bulk hydrogels in the fractures. Interestingly, our granular hydrogels showed recross-linking independence on carrying fluids, contrary to prior reported fluid-dependent recross-linking granular hydrogels. The recross-linking of nanogelators and granular hydrogels can be accomplished from room temperature to 130 °C. The nanocomposite hydrogels displayed increased shear elastic moduli compared to pristine anionic granular hydrogels, probably due to the increased covalent cross-links formed by the homogeneous regenerative approach. We found that the granular hydrogels had high salinity tolerance even in the presence of 1000 ppm divalent ions of calcium (Ca2+) since Ca2+ ions often act as the cross-linker for partially hydrolyzed acrylamide-based hydrogels. Overall, we obtained new regenerative nanocomposite hydrogels based on cationic nanogelators and anionic granular hydrogels for fracture treatments.

RESUMEN

Oral diseases encompassing conditions such as oral cancer, periodontitis, and endodontic infections pose significant challenges due to the oral cavity's susceptibility to pathogenic bacteria and infectious agents. Saliva, a key component of the oral environment, can compromise drug efficacy during oral disease treatment by diluting drug formulations and reducing drug-site interactions. Thus, it is imperative to develop effective drug delivery methods. Stimuli-responsive nanocomposite hydrogels offer a promising solution by adapting to changes in environmental conditions during disease states, thereby enabling targeted drug delivery. These smart drug delivery systems have the potential to enhance drug efficacy, minimize adverse reactions, reduce administration frequency, and improve patient compliance, thus facilitating a faster recovery. This review explores various types of stimuli-responsive nanocomposite hydrogels tailored for smart drug delivery, with a specific focus on their applications in managing oral diseases.

RESUMEN

Despite critical advances in regenerative medicine, the generation of definitive, reliable treatments for musculoskeletal diseases remains challenging. Gene therapy based on the delivery of therapeutic genetic sequences has strong value to offer effective, durable options to decisively manage such disorders. Furthermore, scaffold-mediated gene therapy provides powerful alternatives to overcome hurdles associated with classical gene therapy, allowing for the spatiotemporal delivery of candidate genes to sites of injury. Among the many scaffolds for musculoskeletal research, hydrogels raised increasing attention in addition to other potent systems (solid, hybrid scaffolds) due to their versatility and competence as drug and cell carriers in tissue engineering and wound dressing. Attractive functionalities of hydrogels for musculoskeletal therapy include their injectability, stimuli-responsiveness, self-healing, and nanocomposition that may further allow to upgrade of them as "intelligently" efficient and mechanically strong platforms, rather than as just inert vehicles. Such functionalized hydrogels may also be tuned to successfully transfer therapeutic genes in a minimally invasive manner in order to protect their cargos and allow for their long-term effects. In light of such features, this review focuses on functionalized hydrogels and demonstrates their competence for the treatment of musculoskeletal disorders using gene therapy procedures, from gene therapy principles to hydrogel functionalization methods and applications of hydrogel-mediated gene therapy for musculoskeletal disorders, while remaining challenges are being discussed in the perspective of translation in patients. STATEMENT OF SIGNIFICANCE: Despite advances in regenerative medicine, the generation of definitive, reliable treatments for musculoskeletal diseases remains challenging. Gene therapy has strong value in offering effective, durable options to decisively manage such disorders. Scaffold-mediated gene therapy provides powerful alternatives to overcome hurdles associated with classical gene therapy. Among many scaffolds for musculoskeletal research, hydrogels raised increasing attention. Functionalities including injectability, stimuli-responsiveness, and self-healing, tune them as "intelligently" efficient and mechanically strong platforms, rather than as just inert vehicles. This review introduces functionalized hydrogels for musculoskeletal disorder treatment using gene therapy procedures, from gene therapy principles to functionalized hydrogels and applications of hydrogel-mediated gene therapy for musculoskeletal disorders, while remaining challenges are discussed from the perspective of translation in patients.

Asunto(s)

Técnicas de Transferencia de Gen , Terapia Genética , Hidrogeles , Enfermedades Musculoesqueléticas , Hidrogeles/química , Humanos , Enfermedades Musculoesqueléticas/terapia , Enfermedades Musculoesqueléticas/genética , Terapia Genética/métodos , Animales , Ingeniería de Tejidos/métodos

RESUMEN

The ability of bone biomaterials to promote osteogenic differentiation is crucial for the repair and regeneration of osseous tissue. The development of a temporary bone substitute is of major importance in enhancing the growth and differentiation of human-derived stem cells into an osteogenic lineage. In this study, nanocomposite hydrogels composed of gelatin methacryloyl (GelMA), bioactive glass (BG), and multiwall carbon nanotubes (MWCNT) were developed to create a bone biomaterial that mimics the structural and electrically conductive nature of bone that can promote the differentiation of human-derived stem cells. GelMA-BG-MWCNT nanocomposite hydrogels supported mesenchymal stem cells derived from human induced pluripotent stem cells, hereinafter named iMSCs. Cell adhesion was improved upon coating nanocomposite hydrogels with fibronectin and was further enhanced when seeding pre-differentiated iMSCs. Osteogenic differentiation and mature mineralization were promoted in GelMA-BG-MWCNT nanocomposite hydrogels and were most evidently observed in the 70-30-2 hydrogels, which could be due to the stiff topography characteristic from the addition of MWCNT. Overall, the results of this study showed that GelMA-BG-MWCNT nanocomposite hydrogels coated with fibronectin possessed a favorable environment in which pre-differentiated iMSCs could better attach, proliferate, and further mature into an osteogenic lineage, which was crucial for the repair and regeneration of bone.

RESUMEN

Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle-hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 °C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol-gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe-needle systems with acceptable force (2.2-13.4 N) and work (49.5-317.7 N·mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 °C and underwent rapid gelation at 37 °C. However, their sterilized counterparts gelled at 1-2 °C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery.

RESUMEN

The limited mechanical properties of biopolymer-based hydrogels have hindered their widespread applications in biomedicine and tissue engineering. In recent years, researchers have shown significant interest in developing novel approaches to enhance the mechanical performance of hydrogels. This review focuses on key strategies for enhancing mechanical properties of hydrogels, including dual-crosslinking, double networks, and nanocomposite hydrogels, with a comprehensive analysis of their underlying mechanisms, benefits, and limitations. It also introduces the classic application scenarios of biopolymer-based hydrogels and the direction of future research efforts, including wound dressings and tissue engineering based on 3D bioprinting. This review is expected to deepen the understanding of the structure-mechanical performance-function relationship of hydrogels and guide the further study of their biomedical applications.

Asunto(s)

Hidrogeles , Ingeniería de Tejidos , Hidrogeles/química , Biopolímeros/química , Ingeniería de Tejidos/métodos , Humanos , Fenómenos Mecánicos , Nanocompuestos/química , Materiales Biocompatibles/química , Animales , Impresión Tridimensional , Bioimpresión/métodos

RESUMEN

Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene-based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force-tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high-efficient movement, pre-orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high-orientation MXene-rich layer (orientation degree, f = 0.83) and a polymer-rich layer. The authors demonstrate that MXene-based nanocomposite hydrogels leverage their high-orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super-low MXene of 0.3 wt%, surpassing most hydrogels-based electromagnetic shielding materials. This versatile supergravity-steered strategy can be further extended to arbitrary nanosheets including MoS2, GO, and C3N4, offering a paradigm in the development of oriented nanocomposites.

RESUMEN

In this study, nanochitosan dots (ChiDs) were synthesized using gamma rays and encapsulated in bacterial cellulose (BC) polymer matrix for antibiofilm potential in photodynamic therapy. The composites were analyzed for structural changes using SEM, AFM, FTIR, XRD, EPR, and porosity measurements. Additionally, ChiD release was assessed. The results showed that the chemical composition remained unaltered, but ChiD agglomerates embedded in BC changed shape (1.5-2.5 µm). Bacterial cellulose fibers became deformed and interconnected, with increased surface roughness and porosity and decreased crystallinity. No singlet oxygen formation was observed, and the total amount of released ChiD was up to 16.10%. Antibiofilm activity was higher under green light, with reductions ranging from 48 to 57% under blue light and 78 to 85% under green light. Methicillin-resistant Staphylococcus aureus was the most sensitive strain. The new photoactive composite hydrogels show promising potential for combating biofilm-related infections.

RESUMEN

The interactive flexible device, which monitors the human motion in optical and electrical synergistic modes, has attracted growing attention recently. The incorporation of information attribute within the optical signal is deemed advantageous for improving the interactive efficiency. Therefore, the development of wearable optical information-electronic strain sensors holds substantial promise, but integrating and synergizing various functions and realizing strain-mediated information transformation keep challenging. Herein, an amylopectin (AP) modified nanoclay/polyacrylamide-based nanocomposite (NC) hydrogel and an aggregation-induced-emission-active ink are fabricated. Through the fluorescence-transfer printing of the ink onto the hydrogel film in different strains with nested multiple symbolic information, a wearable interactive fluorescent information-electronic strain sensor is developed. In the sensor, the nanoclay plays a synergistic "one-stone-three-birds" role, contributing to "lightening" fluorescence (≈80 times emission intensity enhancement), ionic conductivity, and excellent stretchability (>1000%). The sensor has high biocompatibility, resilience (elastic recovery ratio: 97.8%), and strain sensitivity (gauge factor (GF): 10.9). Additionally, the AP endows the sensor with skin adhesiveness. The sensor can achieve electrical monitoring of human joint movements while displaying interactive fluorescent information transformation. This research poses an efficient strategy to develop multifunctional materials and provides a general platform for achieving next-generation interactive devices with prospective applications in wearable devices, human-machine interfaces, and artificial intelligence.

Asunto(s)

Conductividad Eléctrica , Hidrogeles , Nanocompuestos , Dispositivos Electrónicos Vestibles , Hidrogeles/química , Nanocompuestos/química , Humanos , Fluorescencia , Resinas Acrílicas/química , Adhesivos/química , Impresión

RESUMEN

Complex wound repair due to tumor recurrence and infection following tumor resection presents significant clinical challenges. In this study, a bifunctional nanocomposite immune hydrogel dressing, SerMA-LJC, is developed to address the issues associated with repairing infected damaged tissues and preventing tumor recurrence. Specifically, the immune dressing is composed of methacrylic anhydride-modified sericin (SerMA) and self-assembled nanoparticles (LJC) containing lonidamine (Lon), JQ1, and chlorine e6 (Ce6). In vitro and in vivo experiments demonstrate that the nanocomposite hydrogel dressing can trigger immunogenic cell death (ICD) and has a potent anti-tumor effect. Moreover, this dressing can mitigate the acidic microenvironment of tumor cells and suppress the overexpression of PD-L1 on the tumor cell surface, thereby altering the immunosuppressive tumor microenvironment and augmenting the anti-tumor immune response. Further, the RNA sequencing analysis revealed that the hydrogel dressing significantly impacts pathways associated with positive regulation of immune response, apoptotic process, and other relevant pathways, thus triggering a potent anti-tumor immune response. More importantly, the dressing generates a substantial amount of reactive oxygen species (ROS), which can effectively kill Staphylococcus aureus and promote infectious wound healing. In conclusion, this dual-function nanocomposite immune hydrogel dressing exhibits promise in preventing tumor recurrence and promoting infectious wound healing.

Asunto(s)

Nanocompuestos , Nanocompuestos/química , Animales , Recurrencia Local de Neoplasia/prevención & control , Ratones , Hidrogeles/química , Vendajes , Melanoma/patología , Línea Celular Tumoral , Staphylococcus aureus/efectos de los fármacos , Humanos , Inyecciones , Microambiente Tumoral/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Due to the severity and high prevalence of cancer, as well as its complex pathological condition, new strategies for cancer treatment and diagnostics are required. As such, it is important to design a toolbox that integrates multiple functions on a single smart platform. Theranostic hydrogels offer an innovative and personalized method to tackle cancer while also considering patient comfort, thereby facilitating future implementation and translation to the clinic. In terms of theranostic systems used in cancer therapy, nanoparticles are widely used as diagnostic and therapeutic tools. Nanoparticles can achieve systemic circulation, evade host defenses, and deliver drugs and signaling agents at the targeted site, to diagnose and treat the disease at a cellular and molecular level. In this context, hydrogel microneedles have a high potential for multifunctional operation in medical devices, while avoiding the complications associated with the systemic delivery of therapeutics. Compared with oral administration and subcutaneous injection, microneedles offer advantages such as better patient compliance, faster onset of action, and improved permeability and efficacy. In addition, they comprise highly biocompatible polymers with excellent degradability and tunable properties. Nanoparticles and microneedles thus offer the possibility to expand the theranostic potential through combined synergistic use of their respective features. We review herein recent advances concerning processing methods and material requirements within the realm of hydrogel microneedles as theranostic platforms, various approaches toward cancer therapy, and the incorporation of nanoparticles for added functionality.

Asunto(s)

Hidrogeles , Nanocompuestos , Agujas , Medicina de Precisión , Nanomedicina Teranóstica , Humanos , Hidrogeles/administración & dosificación , Hidrogeles/química , Nanomedicina Teranóstica/métodos , Animales , Nanocompuestos/administración & dosificación , Nanocompuestos/química , Sistemas de Liberación de Medicamentos/instrumentación , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/terapia , Microinyecciones/instrumentación

RESUMEN

Lanthanide-containing nanomaterials have gained significant popularity for their utilization in polymeric networks, enabling the creation of luminescent nanocomposites for advanced applications. In this study, we developed a new type of lanthanide-containing nanocomposite hydrogels by incorporating terbium-containing laponite (Tb3+@Lap) into the networks of polyethyleneimine-modified gelatin/polydextran aldehyde (PG/PDA) through dynamic bonds. The structures and properties of the Tb3+@Lap-containing nanocomposite double-network (ncDN) hydrogels were comprehensively investigated in comparison with the DN hydrogels with a pure polymeric network and the Lap-containing ncDN hydrogels. The PG/PDA/Tb3+@Lap ncDN hydrogels with multiple dynamic bonds (i.e., imine bonds, coordination bonds, hydrogen bonds, and electrostatic interactions) exhibited remarkable characteristics of shear-thinning and self-healing, making them suitable for the construction of hydrogel scaffolds on a macroscale using fabrication techniques such as electrospinning and 3D printing. Moreover, the PG/PDA/Tb3+@Lap ncDN hydrogels have been demonstrated to act as sensitive and selective luminescent sensors for detecting copper ions. Taken together, a versatile lanthanide-containing ncDN hydrogel platform capable of dynamic features is developed for processing and sensing applications.

Asunto(s)

Elementos de la Serie de los Lantanoides , Nanocompuestos , Silicatos , Gelatina/química , Hidrogeles/química , Nanocompuestos/química , Polímeros

RESUMEN

Nanotechnology has emerged as the eminent focus of today's research to overcome challenges related to conventional drug delivery systems. A wide spectrum of novel delivery systems has been investigated to improve the therapeutic outcomes of drugs. The polymer-based nanocomposite hydrogels (NCHs) that have evolved as efficient carriers for controlled drug delivery are of particular interest in this regard. Nanocomposites amalgamate the properties of both nanoparticles (NPs) as well as hydrogels, exhibiting superior functionalities over conventional hydrogels. This multiple functionality is based upon advanced mechanical, electrical, optical as well as magnetic properties. Here is a brief overview of the various types of nanocomposites, such as NCHs based on Carbon-bearing nanomaterials, polymeric nanoparticles, inorganic nanoparticles, and metal and metal-oxide NPs. Accordingly, this article will review numerous ways of preparing these NCHs with particular emphasis on the vast biomedical applications displayed by them in numerous fields such as tissue engineering, drug delivery, wound healing, bioprinting, biosensing, imaging and gene silencing, cancer therapy, antibacterial therapy, etc. Moreover, various features can be tuned, based on the final application, by controlling the chemical composition of hydrogel network, which may also influence the released conduct. Subsequently, the recent work and future prospects of this newly emerging class of drug delivery system have been enlisted.

Asunto(s)

Sistemas de Liberación de Medicamentos , Polímeros , Humanos , Nanogeles , Disponibilidad Biológica , Polímeros/química , Hidrogeles/química

RESUMEN

In osteosarcoma, immunotherapy often faces hurdles posed by cancer-associated fibroblasts (CAFs) that secrete dense extracellular matrix components and cytokines. Directly removing CAFs may prove ineffective and even promote tumor metastasis. To address this challenge, a sequential nanocomposite hydrogel that reshapes CAF behavior is developed, enhancing tumor-infiltrating T-cells in osteosarcoma. The approach utilizes an injectable blend of carboxymethyl chitosan and tetrabasic polyethylene glycol, forming a hydrogel for controlled release of a potent CAF suppressor (Nox4 inhibitor, Nox4i) and liposomal Doxorubicin (L-Dox) to induce immunogenic cell death (ICD) upon in situ administration. Nox4i effectively counters CAF activation, overcoming T-cell exclusion mechanisms, followed by programmed L-Dox release for ICD induction in stroma-rich osteosarcoma models. Combining the co-delivery gel with αPD-1 checkpoint inhibitor further enhances its effectiveness in an orthotopic osteosarcoma model. Immunophenotyping data underscore a significant boost in tumor T-cell infiltration and favorable anti-tumor immunity at the whole-animal level.

Asunto(s)

Neoplasias Óseas , Fibroblastos Asociados al Cáncer , Doxorrubicina/análogos & derivados , Osteosarcoma , Animales , Nanogeles , Fibroblastos Asociados al Cáncer/patología , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Hidrogeles/farmacología , Neoplasias Óseas/tratamiento farmacológico , Inmunoterapia , Línea Celular Tumoral , Microambiente Tumoral , Polietilenglicoles

RESUMEN

Hydrogels are three-dimensional (3D) water-swellable polymeric matrices that are used extensively in tissue engineering and drug delivery. Hydrogels can be conformed into any desirable shape using 3D bio-printing, making them suitable for personalized treatment. Among the different 3D bio-printing techniques, digital light processing (DLP)-based printing offers the advantage of quickly fabricating high resolution structures, reducing the chances of cell damage during the printing process. Here, we have used DLP to 3D bio-print biocompatible gelatin methacrylate (GelMA) scaffolds intended for bone repair. GelMA is biocompatible, biodegradable, has integrin binding motifs that promote cell adhesion, and can be crosslinked easily to form hydrogels. However, GelMA on its own is incapable of promoting bone repair and must be supplemented with pharmaceutical molecules or growth factors, which can be toxic or expensive. To overcome this limitation, we introduced zinc-based metal-organic framework (MOF) nanoparticles into GelMA that can promote osteogenic differentiation, providing safer and more affordable alternatives to traditional methods. Incorporation of this nanoparticle into GelMA hydrogel has demonstrated significant improvement across multiple aspects, including bio-printability, and favorable mechanical properties (showing a significant increase in the compressive modulus from 52.14 ± 19.42 kPa to 128.13 ± 19.46 kPa with the addition of ZIF-8 nanoparticles). The designed nanocomposite hydrogels can also sustain drug (vancomycin) release (maximum 87.52 ± 1.6% cumulative amount) and exhibit a remarkable ability to differentiate human adipose-derived mesenchymal stem cells toward the osteogenic lineage. Furthermore, the formulated MOF-integrated nanocomposite hydrogel offers the unique capability to coat metallic implants intended for bone healing. Overall, the remarkable printability and coating ability displayed by the nanocomposite hydrogel presents itself as a promising candidate for drug delivery, cell delivery and bone tissue engineering applications.

RESUMEN

Hydrogels can be considered as mimics of the extracellular matrix (ECM). Through integrins, the cytoskeleton is connected to the ECM, and cytoskeleton tension depends on ECM stiffness. A number of age-related diseases depend on cellular processes related to cytoskeleton function. Some examples of cancer initiation and progression and heart disease in relation to ECM stiffness have been analyzed. The incorporation of rigid particles into the ECM can increase ECM stiffness and promote the formation of internal residual stresses. Water migration, changes in water binding energy to biomactomolecules, and changes in the state of water from tightly bound water to free and loosely bound water lead to changes in the stiffness of the ECM. Cardiac tissue engineering, ECM stiffness and cancer, the equivalence of ECM stiffness, oxidative stress, inflammation, multi-layer polyelectrolyte complex hydrogels and bioprinting, residual internal stresses, viscoelastic hydrogels, hydrogel nanocomposites, and the effect of water have been reported. Special attention has been paid to the role of bound water and internal stresses in ECM stiffness. The risks related to rigid particle incorporation into the ECM have been discussed. The potential effect of polyphenols, chitosan, and chitosan oligosaccharide on ECM stiffness and the potential for anti-TNF-α and anti-NF-κB therapies have been discussed.

RESUMEN

Hydrogels with great biocompatibility, biodegradability, and mechanical properties, combined with osteoconductivity, osteoinductivity, and osteointegration as biomaterials for bone regeneration without adding exogenous growth factors and cells are highly appealing but challenging. Here, inspired by organic-inorganic analogues of natural bone tissue and the adhesion chemistry of mussels, nanocomposite hydrogels with self-healing, injectable, adhesive, antioxidant, and osteoinductive properties (termed GO-PHA-CPs) were constructed by Schiff base cross-linking between dopamine-modified gelatin (Gel-DA) and oxidized dextran (ODex). Furthermore, the hydrogel network was enhanced by the introduction of polydopamine-functionalized nanohydroxyapatite (PHA) by improving the interfacial compatibility between the rigid inorganic particles and the flexible hydrogel matrix. Bioactive cod peptides (CPs) with osteogenic activity from Atlantic cod were further incorporated into the nanocomposite hydrogel. As a result, the multicomponent nanocomposite hydrogel favored the adhesion and spreading of MC3T3-E1 cells. The increased ALP activity suggested that GO-PHA-CPs hydrogels contributed to the osteogenic differentiation of MC3T3-E1 cells. The suitability of GO-PHA-CPs hydrogels for enhancing bone regeneration in vivo was further confirmed by the rat femoral defect model. Our results indicate that the multifunctional GO-PHA-CPs nanocomposite hydrogels without growth factors are a promising and effective candidate material for bone regeneration.

RESUMEN

Flexible intelligent actuators with the characteristics of flexibility, safety and scalability, are highly promising in industrial production, biomedical fields, environmental monitoring, and soft robots. Nanocomposite hydrogels are attractive candidates for soft actuators due to their high pliability, intelligent responsiveness, and capability to execute large-scale rapid reversible deformations under external stimuli. Here, the recent advances of nanocomposite hydrogels as soft actuators are reviewed and focus is on the construction of elaborate and programmable structures by the assembly of nano-objects in the hydrogel matrix. With the help of inducing the gradient or oriented distributions of the nanounits during the gelation process by the external forces or molecular interactions, nanocomposite hydrogels with ordered structures are achieved, which can perform bending, spiraling, patterned deformations, and biomimetic complex shape changes. Given great advantages of these intricate yet programmable shape-morphing, nanocomposite hydrogel actuators have presented high potentials in the fields of moving robots, energy collectors, and biomedicines. In the end, the challenges and future perspectives of this emerging field of nanocomposite hydrogel actuators are proposed.