1,721,003 research outputs found
New biodegradable dextran-based hydrogels for protein delivery: Synthesis and characterization
No full textA new derivative of dextran grafted with polyethylene glycol methacrylate through a carbonate bond (DEX–PEG–MA) has been synthesized and characterized. The photo-crosslinking reaction of DEX–PEG–MA allowed the obtainment of biodegradable networks tested for their mechanical and release properties. The new hydrogels were compared with those made of dextran methacrylate (DEX–MA), often employed as drug delivery systems of small molecules. The inclusion of PEG as a spacer created additional interactions among the polymeric chains improving the extreme fragility and lack of hardness typical of gels made of DEX–MA. Moreover, the different behavior in terms of swelling and degradability of the networks was able to affectthe release of a model macromolecule over time, laking DEX–PEG–MA matrices suitable candidates for the delivery of high molecular weight peptides. Interestingly, the combination of the two dextran derivatives showed intermediate ability to modulate the release of high molecular weight macromolecules
Self-healing DNA-based injectable hydrogels with reversible covalent linkages for controlled drug delivery
No full textInjectable hydrogels represent a valuable tool for the delivery of therapeutic molecules aimed to restore the functionality of damaged tissues. In this study, we report the design of a nanocomposite DNA-based hydrogel crosslinked with oxidized alginate (OA) via the formation of reversible imine linkages. The formulated hydrogel functioned as an injectable carrier for the sustained delivery of a small molecule drug, simvastatin. The degree of oxidation of alginate and the concentration of silicate-based nanoparticles (nSi) were varied to modulate the rheological properties of the hydrogels. Specifically, the formulations consisting of OA with higher degree of oxidation displayed the highest value of storage moduli, yield stress, yield strain, and rapid recovery after removal of cyclic stress. The hydrogel formulations exhibited self-healing and shear-thinning properties due to the reversible nature of the covalent imine bonds formed between the aldehyde groups of OA and the amine groups present in the DNA nucleotides. Moreover, the incorporation of charged nSi further enhanced the shear strength of the formulated hydrogels by establishing electrostatic interactions with the phosphate groups of the DNA network. The optimized hydrogel was able to promote the sustained release of simvastatin for more than a week. The bioactivity of the released drug was confirmed by testing its ability to induce osteogenic differentiation and migration of human adipose-derived stem cells in vitro. Overall, the results obtained from this study demonstrate that DNA could be used as a natural biopolymer to fabricate self-healing injectable hydrogels with sustained release properties for minimally invasive therapeutic approaches.Statement of significanceDynamic covalent chemistry, especially Schiff base reactions have emerged as a promising route for the formation of injectable hydrogels. Our study demonstrated the development of a DNA-based self-healing hydrogel formed via Schiff base reaction occurring at physiological conditions. The hydrogels functioned as sustained delivery vehicles for the hydrophobic drug simvastatin, which requires a polymeric carrier for controlled delivery of therapeutic concentrations of the drug without exhibiting cytotoxic effects. Presently available hydrogel-based drug delivery systems encounter major challenges for the delivery of hydrophobic drugs due to the hydrophilic nature of the base matrix. Our strategy presents a platform technology for the design of minimally invasive approaches for the sustained delivery of hydrophobic drugs similar to simvastatin. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved
Nucleic Acid-Based Dual Cross-Linked Hydrogels for in Situ Tissue Repair via Directional Stem Cell Migration
No full textIn situ tissue repair holds great potential as a cell-free regenerative strategy. A critical aspect of this approach is the selection of cell instructive materials that can efficiently regulate the defect microenvironment via the release of chemoattractant factors to mobilize and recruit endogenous stem cells toward the site of implantation. Here we report the design of a DNA-based hydrogel as a drug delivery platform for the sustained release of a promising chemoattractant, SDF-1 alpha. The hydrogel is composed of chemically cross-linked DNA strands, which are bridged via silicate nanodisks (nSi). Silicate nanodisks electrostatically interact with the negatively charged DNA backbone resulting in the formation of a dual cross-linked nanocomposite hydrogel with a combination of chemical and physical cross-link points. The formulated nanocomposites display enhanced elasticity and mechanical toughness as compared to their nonsilicate containing counterparts. Moreover, the electrostatic interaction between nSi and SDF-1 alpha leads to sustained release of the chemokine from the hydrogels. The in vitro bioactivity assays confirm the retention of chemotactic properties of the protein after its release. Overall, the dual cross-linked DNA-based hydrogel platform could be potentially used as a cell-instructive material for the recruitment of host stem cells to guide the process of in situ tissue repair
Multifunctional nanodiamonds in regenerative medicine: recent advances and future directions
No full textWith recent advances in the field of nanomedicine, many new strategies have emerged for diagnosing and treating diseases. At the forefront of this multidisciplinary research, carbon nanomaterials have demonstrated unprecedented potential for a variety of regenerative medicine applications including novel drug delivery platforms that facilitate the localized and sustained release of therapeutics. Nanodiamonds (NDs) are a unique class of carbon nanoparticles that are gaining increasing attention for their biocompatibility, highly functional surfaces, optical properties, and robust physical properties. Their remarkable features have established NDs as an invaluable regenerative medicine platform, with a broad range of clinically relevant applications ranging from targeted delivery systems for insoluble drugs, bioactive substrates for stem cells, and fluorescent probes for long-term tracking of cells and biomolecules in vitro and in vivo. This review introduces the synthesis techniques and the various routes of surface functionalization that allow for precise control over the properties of NDs. It also provides an in-depth overview of the current progress made toward the use of NDs in the fields of drug delivery, tissue engineering, and bioimaging. Their future outlook in regenerative medicine including the current clinical significance of NDs, as well as the challenges that must be overcome to successfully translate the reviewed technologies from research platforms to clinical therapies will also be discussed. © 2017 Elsevier B.V
Bioactive Hydrogel Platforms for Spatiotemporal Delivery of Baculoviruses in Biomedical Applications
No full textBaculoviruses offer a multitude of advantages over other gene carriers due to their non-pathogenicity and inability to replicate in mammalian cells, ease of production, and high transduction efficiencies. To expand their functionality in vivo, baculoviruses containing mammalian transcription promoters (BacMam) can be physically entrapped within biocompatible hydrogels to modulate their release and transduction efficiency. The present work demonstrates several techniques in which BacMam viruses can be encapsulated and delivered in fibrin gel, an FDA-approved sealant and adhesive with numerous clinical applications, to provide spatiotemporal control over the delivery of BacMam viruses to mammalian cells. Fibrin is shown to be an effective biomaterial carrier for the delivery of BacMam viruses to mammalian cells growing in 2D culture, 3D culture, and in the co-delivery of stem cells and baculoviruses in the aerosolized delivery of fibrin films. Overall, the results of this work provide a valuable insight on the therapeutic potential of fibrin gels for in vivo BacMam-mediated gene delivery in regenerative medicine
Musculoskeletal Tissue Engineering: Tendon, Ligament, and Skeletal Muscle Replacement and Repair
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