A Visible Light Cross-Linked Underwater Hydrogel Adhesive with Biodegradation and Hemostatic Ability.

Hydrogel adhesives with integrated functionalities are still required to match their ever-expanding practical applications in the field of tissue repair and regeneration. A simple and effective safety strategy is reported, involving an in situ injectable polymer precursor and visible light-induced cross-linking. This strategy enables the preparation of a hydrogel adhesive in a physiological environment, offering wet adhesion to tissue surfaces, molecular flexibility, biodegradability, biocompatibility, efficient hemostatic performance, and the ability to facilitate liver injury repair. The proposed one-step preparation process of this polymer precursor involves the mixing of gelatin methacryloyl (GelMA), poly(thioctic acid) [P(TA)], poly(acrylic acid)/amorphous calcium phosphate (PAAc/ACP, PA) and FDA-approved photoinitiator solution, and a subsequent visible light irradiation after in situ injection into target tissues that resulted in a chemically-physically cross-linked hybrid hydrogel adhesive. Such a combined strategy shows promise for medical scenarios, such as uncontrollable post-traumatic bleeding.

Sprayable and injectable visible-light Kappa-carrageenan hydrogel for in-situ soft tissue engineering.

The aim of this study was to develop injectable and sprayable visible-light crosslinked Kappa-carrageenan (κCA) hydrogel and to investigate the role of polymer concentration (2, 4 and 6 wt%) and degree of methacrylation (6 and 12%) on its properties. It was found that, the average pore sizes, water content and swelling ratio of hydrogel were tunable by changing the methacrylate κCA (KaMA) concentration and methacrylation degree. Furthermore, the mechanical properties of KaMA could be noticeably modulated, depending on the formulation of hydrogel. Tensile and comprehensive modules were enhanced from 68 to 357 kPa and from 213 to 357 kPa, respectively, by increasing KaMA concentration from 2 to 6 wt% and methacrylation degree from 6 to 12%. Furthermore, with increasing methacrylation degree and polymer content, the absorbed energy and energy loss were increased. Moreover, recovery significantly enhanced from 27.3% to 74.4% with increasing polymer content from 2 to 6 wt%. Finally, visible-light crosslinked KaMA hydrogels not only was biocompatible, but also could promote HaLa cell and fibloblasts function. The visible-light crosslinked KaMA is thought to be an exclusive biomaterial as a sprayable hydrogel being able to cover skin injuries or to inject as a bio-printing material to in situ heal soft tissue damages.

Three-Dimensional Printing of a Tyramine Hyaluronan Derivative with Double Gelation Mechanism for Independent Tuning of Shear Thinning and Postprinting Curing.

Biofabrication via three-dimensional printing (3DP) is expanding our capabilities of producing tissue engineering constructs for regenerative medicine, personalized medicine, and engineered tissue models of disease and diagnostics. Hydrogel-based materials for extrusion-based printing have been introduced; nevertheless, it is still challenging to combine into a single biomaterial all the requirements of an ink. These inks need to flow for extrusion under low shear, yet have immediate shape retention after deposition, provide a biochemical environment similar to that of physiological extracellular matrix, and a curing mechanism avoiding cell damage. This work introduces a simple and versatile tyramine-modified hyaluronan material (HA-Tyr) for extrusion-based printing, featured by (i) single component yet two distinct cross-linking mechanisms, allowing (ii) shear-thinning tuning independently of the postprinting curing; (iii) no rheological additives or sacrificial components; (iv) curing with visible light for shape stability; (v) possibility to postfunctionalize; and (vi) preservation of hyaluronan structure owing to low modification degree. The ink is based on a hydroxyphenol hyaluronan derivative, where the shear thinning properties are determined by the enzymatic cross-linking, while the final shape fixation is achieved with visible light in the presence of Eosin Y as photosensitizer. The two cross-linking mechanisms are totally independent. A universal rheologically measurable parameter giving a quantitative measure of the "printability" was introduced and employed for identifying best printability range within the parameter space in a quantitative manner. 3DP constructs were postfunctionalized, and cell-laden constructs were produced. Due to its simplicity and versatility, HA-Tyr can be used for producing a wide variety of 3D printing constructs for tissue engineering applications.

Anticancer Therapeutic Alginate-Based Tissue Sealants for Lung Repair.

Injury to the connective tissue that lines the lung, the pleura, or the lung itself can occur from many causes including trauma or surgery, as well as lung diseases or cancers. To address current limitations for patching lung injuries, to stop air or fluid leaks, an adherent hydrogel sealant patch system was developed, based on methacrylated alginate (AMA) and AMA dialdehyde (AMA-DA) blends, which is capable of sealing damaged tissues and sustaining physiological pressures. Methacrylation of alginate hydroxyl groups rendered the polysaccharide capable of photo-cross-linking when mixed with an eosin Y-based photoinitiator system and exposed to visible green light. Oxidation of alginate yields functional aldehyde groups capable of imine bond formation with proteins found in many tissues. The alginate-based patch system was rigorously tested on a custom burst pressure testing device. Blending of nonoxidized material with oxidized (aldehyde modified) alginates yielded patches with improved burst pressure performance and decreased delamination as compared with pure AMA. Human mesothelial cell (MeT-5A) viability and cytotoxicity were retained when cultured with the hydrogel patches. The release and bioactivity of doxorubicin-encapsulated submicrospheres enabled the fabrication of drug-eluting adhesive patches and were effective in decreasing human lung cancer cell (A549) viability.

Dual-Cross-Linked Methacrylated Alginate Sub-Microspheres for Intracellular Chemotherapeutic Delivery.

Intracellular delivery vehicles comprised of methacrylated alginate (Alg-MA) were developed for the internalization and release of doxorubicin hydrochloride (DOX). Alg-MA was synthesized via an anhydrous reaction, and a mixture of Alg-MA and DOX was formed into sub-microspheres using a water/oil emulsion. Covalently cross-linked sub-microspheres were formed via exposure to green light, in order to investigate effects of cross-linking on drug release and cell internalization, compared to traditional techniques, such as ultraviolet (UV) light irradiation. Cross-linking was performed using light exposure alone or in combination with ionic cross-linking using calcium chloride (CaCl2). Alg-MA sub-microsphere diameters were between 88 and 617 nm, and ζ-potentials were between -20 and -37 mV. Using human lung epithelial carcinoma cells (A549) as a model, cellular internalization was confirmed using flow cytometry; different sub-microsphere formulations varied the efficiency of internalization, with UV-cross-linked sub-microspheres achieving the highest internalization percentages. While blank (nonloaded) Alg-MA submicrospheres were noncytotoxic to A549 cells, DOX-loaded sub-microspheres significantly reduced mitochondrial activity after 5 days of culture. Photo-cross-linked Alg-MA sub-microspheres may be a potential chemotherapeutic delivery system for cancer treatment.