Injectable Self-Oxygenating Cardio-Protective and Tissue Adhesive Silk-Based Hydrogel for Alleviating Ischemia After Mi Injury.

Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.

Injectable and self-healing dual crosslinked gelatin/kappa-carrageenan methacryloyl hybrid hydrogels via host-guest supramolecular interaction for wound healing.

Injectable hydrogels based on natural polymers have shown great potential for various tissue engineering applications, such as wound healing. However, poor mechanical properties and weak self-healing ability are still major challenges. In this work, we introduce a host-guest (HG) supramolecular interaction between acrylate-ß-cyclodextrin (Ac-ß-CD) conjugated on methacrylated kappa-carrageenan (MA-κ-CA) and aromatic residues on gelatin to provide self-healing characteristics. We synthesize an MA-κ-CA to conjugate Ac-ß-CD and fabricate dual crosslinked hybrid hydrogels with gelatin to mimic the native extracellular matrix (ECM). The dual crosslinking occurs on the MA-κ-CA backbone through the addition of KCl and photocrosslinking process, which enhances mechanical strength and stability. The hybrid hydrogels exhibit shear-thinning, self-healing, and injectable behavior, which apply easily under a minimally invasive manner and contribute to shear stress during the injection. In-vitro studies indicate enhanced cell viability. Furthermore, scratch assays are performed to examine cell migration and cell-cell interaction. It is envisioned that the combination of self-healing and injectable dual crosslinked hybrid hydrogels with HG interactions display a promising and functional biomaterial platform for wound healing applications.

Immunomodulating Hydrogels as Stealth Platform for Drug Delivery Applications.

Non-targeted persistent immune activation or suppression by different drug delivery platforms can cause adverse and chronic physiological effects including cancer and arthritis. Therefore, non-toxic materials that do not trigger an immunogenic response during delivery are crucial for safe and effective in vivo treatment. Hydrogels are excellent candidates that can be engineered to control immune responses by modulating biomolecule release/adsorption, improving regeneration of lymphoid tissues, and enhancing function during antigen presentation. This review discusses the aspects of hydrogel-based systems used as drug delivery platforms for various diseases. A detailed investigation on different immunomodulation strategies for various delivery options and deliberate upon the outlook of such drug delivery platforms are conducted.