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 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the primary challenges in extrusion-based 3D bioprinting is the ability to print self-supported multilayered constructs with biocompatible hydrogels. The bioinks should have sufficient post-printing mechanical stability for soft tissue and organ regeneration. Here, we report on the synthesis, characterization and 3D printability of hyaluronic acid (HA)-carboxymethylcellulose (CMC) hydrogels cross-linked through N-acyl-hydrazone bonding. The hydrogel's hydrolytic stability was acquired by the effects of both the prevention of the oxidation of the six-membered rings of HA, and the stabilization of acyl-hydrazone bonds. The shear-thinning and self-healing properties of the hydrogel allowed us to print different 3D constructs (lattice, cubic and tube) of up to 50 layers with superior precision and high post-printing stability without support materials or post-processing depending on their compositions (H7:C3, H5:C5 and H3:C7). Morphological analyses of different zones of the 3D-printed constructs were undertaken for verification of the interconnection of pores. Texture profile analysis (TPA) (hardness (strength), elastic recovery, etc) and cyclic compression studies of the 3D-printed constructs demonstrated exceptional elastic properties and fast recovery after 50% strain, respectively, which have been attributed to the addition of CMC into HA. A model drug quercetin was released in a sustained manner from hydrogels and 3D constructs. In vitro cytotoxicity studies confirmed the excellent cyto-compatibility of these gels. In vivo mice studies prove that these biocompatible hydrogels enhance angiogenesis. The results indicate that controlling the key properties (e.g. self-crosslinking capacity, composition) can lead to the generation of multilayered constructs from 3D-bioprintable HA-CMC hydrogels capable of being leveraged for soft tissue engineering applications.
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PMID:Self-crosslinking hyaluronic acid-carboxymethylcellulose hydrogel enhances multilayered 3D-printed construct shape integrity and mechanical stability for soft tissue engineering. 3262 38

In this study, we developed an injectable antibacterial hydrogel based on hyaluronic acid (HA) and chlorhexidine (CHX) for cardiovascular implantable electronic device (CIED) infection treatment. To balance stability and moldability, the HA scaffold was pre-crosslinked by 1,4-butanediol diglycidyl ether (BDDE) and then ground to form an HA microgel (CHA). Then, the antibacterial agent CHX was further crosslinked in the CHA microgel through electrostatic interactions between CHA and CHX to obtain hybrid crosslinked hydrogels (CHA/CHX). These hydrogels exhibited shear-thinning/self-recovery behavior, allowing easy injection into the CIED pocket and good matching with the pocket shape without extra space requirements, which represents an improvement on previously reported methods. In vitro and in vivo antibacterial tests showed that the CHA/CHX hydrogels had both good biocompatibility and very effective antibacterial action. The above results indicated that the CHA/CHX hydrogels would be an excellent candidate for CIED pocket infection treatment.
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PMID:Hyaluronic acid-based antibacterial hydrogels constructed by a hybrid crosslinking strategy for pacemaker pocket infection prevention. 3271 29

The rapid development of additive manufacturing techniques in the field of tissue regeneration offers unprecedented success for artificial tissue and organ fabrication. However, some limitations still remain for current bioinks, such as the compromised cell viability after printing, the low cross-linking efficiency leading to poor printing resolution and speed due to the relatively slow gelation rate, and the requirement of external stimuli for gelation. To address these problems, herein, a biocompatible and printable instant gelation hydrogel system has been developed based on a designed hyperbranched poly(ethylene glycol) (PEG)-based multihydrazide macro-cross-linker (HB-PEG-HDZ) and an aldehyde-functionalized hyaluronic acid (HA-CHO). HB-PEG-HDZ is prepared by the postfunctionalization of hyperbranched PEG-based multivinyl macromer via thiol-ene chemistry. Owing to the high functional group density of HB-PEG-HDZ, the hydrogel can be formed instantly upon mixing the solutions of two components. The reversible cross-linking mechanism between the hydrazide and aldehyde groups endows the hydrogel with shear-thinning and self-healing properties. The minimally toxic components and cross-linking chemistry allow the resulting hydrogel to be a biocompatible niche. Moreover, the fast sol-to-gel transition of the hydrogel, combining all of the advanced characteristics of this platform, protects the cells during the printing procedure, avoids their damage during extrusion, and improves the transplanted cell survival.
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PMID:Instant Gelation System as Self-Healable and Printable 3D Cell Culture Bioink Based on Dynamic Covalent Chemistry. 3280 52

Shear-thinning, self-healing hydrogels are promising vehicles for therapeutic cargo delivery due to their ability to be injected using minimally invasive surgical procedures. We present an injectable hydrogel using a novel combination of dynamic covalent crosslinking with thermoresponsive engineered proteins. Ex situ at room temperature, rapid gelation occurs through dynamic covalent hydrazone bonds by simply mixing two components: hydrazine-modified elastin-like protein (ELP) and aldehyde-modified hyaluronic acid. This hydrogel provides significant mechanical protection to encapsulated human mesenchymal stem cells during syringe needle injection and rapidly recovers after injection to retain the cells homogeneously within a 3D environment. In situ, the ELP undergoes a thermal phase transition, as confirmed by Coherent anti-Stokes Raman scattering microscopy observation of dense ELP thermal aggregates. The formation of the secondary network reinforces the hydrogel and results in a 10-fold slower erosion rate compared to a control hydrogel without secondary thermal crosslinking. This improved structural integrity enables cell culture for three weeks post injection, and encapsulated cells maintain their ability to differentiate into multiple lineages, including chondrogenic, adipogenic, and osteogenic cell types. Together, these data demonstrate the promising potential of ELP-HA hydrogels for injectable stem cell transplantation and tissue regeneration.
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PMID:Covalently adaptable elastin-like protein - hyaluronic acid (ELP - HA) hybrid hydrogels with secondary thermoresponsive crosslinking for injectable stem cell delivery. 3304 40

Towards the repair of damaged tissues, numerous scaffolds have been fabricated to recreate the complex extracellular matrix (ECM) environment to support desired cell behaviors; however, it is often challenging to design scaffolds with the requisite cell-anchorage sites, mechanical stability, and tailorable physicochemical properties necessary for many applications. To address this and to improve on the properties of hyaluronic acid (HA) hydrogels, we combined photocrosslinkable norbornene-modified HA (NorHA) with human platelet lysate (PL). These PL-NorHA hybrid hydrogels supported the adhesion of cells when compared to NorHA hydrogels without PL, exhibited tailorable physicochemical properties based on the concentration of individual components, and released proteins over time. Using microfluidic techniques with on-chip mixing of NorHA and PL and subsequent photocrosslinking, spherical PL-NorHA microgels with a hierarchical fibrillar network were fabricated that exhibited the sustained delivery of PL proteins. Microgels could be jammed into granular hydrogels that exhibited shear-thinning and self-healing properties, enabling ejection from syringes and the fabrication of stable 3D constructs with 3D printing. Again, the inclusion of PL enhanced cellular interactions with the microgel structures. Overall, the combination of biomolecules and fibrin self-assembly arising from the enriched milieu of PL-derived proteins improved the bioactivity of HA-based hydrogels, enabling the formation of dynamic systems with modular design. The granular systems can be engineered to meet the complex demands of functional tissue repair using versatile processing techniques, such as with 3D printing.
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PMID:Injectable hyaluronic acid and platelet lysate-derived granular hydrogels for biomedical applications. 3313 Mar 9

While drug-loaded microparticles (MPs) can serve as drug reservoirs for sustained drug release and therapeutic effects, needle clogging by MPs poses a challenge for ocular drug delivery via injection. Two polymers commonly used in ophthalmic procedures-hyaluronic acid (HA) and methylcellulose (MC)-have been tested for their applicability for ocular injections. HA and MC were physically blended with sunitinib malate (SUN)-loaded PLGA MPs for subconjunctival (SCT) injection into rat eyes. The HA and MC viscous solutions facilitated injection through fine-gauged needles due to their shear-thinning properties as shown by rheological characterizations. The diffusion barrier presented by HA and MC reduced burst drug release and extended overall release from MPs. The significant level of MP retention in the conjunctiva tissue post-operation confirmed the minimal leakage of MPs following injection. The safety of HA and MC for ocular applications was demonstrated histologically.
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PMID:Shear-Thinning Viscous Materials for Subconjunctival Injection of Microparticles. 3324 86


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