Tuning gelatin-based hydrogel towards bioadhesive ocular tissue engineering applications.

Gelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility, easy processability, transparency, non-toxicity, and reasonable mechanical properties to mimic the extracellular matrix (ECM). Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application. We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor, utilizing epoxide ring-opening reactions and visible light-crosslinking. This chemical modification allows the obtaining of an elastic protein-based hydrogel (GELGYM) with excellent biomimetic properties, approaching those of the native tissue. GELGYM can be modulated to be stretched up to 4 times its initial length and withstand high tensile stresses up to 1.95 MPa with compressive strains as high as 80% compared to Gelatin-methacryloyl (GeIMA), the most studied derivative of gelatin used as a bioadhesive. GELGYM is also highly biocompatible and supports cellular adhesion, proliferation, and migration in both 2 and 3-dimensional cell-cultures. These characteristics along with its super adhesion to biological tissues such as cornea, aorta, heart, muscle, kidney, liver, and spleen suggest widespread applications of this hydrogel in many biomedical areas such as transplantation, tissue adhesive, wound dressing, bioprinting, and drug and cell delivery.

Photo-cross-linked Gelatin Glycidyl Methacrylate/N-Vinylpyrrolidone Copolymeric Hydrogel with Tunable Mechanical Properties for Ocular Tissue Engineering Applications.

Corneal transplantation is currently the primary treatment for corneal blindness. However, severe global scarcity of donor corneas is driving the scientific community to find novel solutions. One potential solution is to replace the damaged tissue with a biocompatible artificial cornea. Here, gelatin glycidyl methacrylate (GM) and N-vinylpyrrolidone (VP) were cocrosslinked to afford a hybrid bicomponent copolymeric hydrogel with excellent mechanical, structural, and biological properties. Our studies showed that the GM/VP ratio can be adjusted to generate a construct with high tensile modulus and strength of 1.6 and 1.0 MPa, respectively, compared to 14 and 7.5 MPa for human cornea. The construct can tolerate up to 22.4 kPa pressure before retention sutures can tear through it. Due to the presence of a synthetic component, it has a significantly higher stability against collagenase induced degradation, yet it is biocompatible and promotes cellular adhesion, proliferation, and migration under in vitro settings.

Palladium catalyzed C-N bond formation in the synthesis of 7-amino-substituted tetracyclines.

A facile synthesis of 7-alkylamino- and 7-cycloalkylaminotetracycline derivatives has been accomplished using an in situ generated aminostannane precursor. This procedure is advantageous in that it allows the concise synthesis of a number of unreported tetracycline derivatives that are cumbersome to prepare through traditional methods. These compounds are crucial to understanding structure activity relationships in the D-ring of tetracycline-type antibiotics and the acquired efflux resistance mechanism to this class of antibiotics.

Synthesis and biological evaluation of 9-substituted tetracycline derivatives.

The synthesis of 9-substituted tetracycline derivatives has been accomplished by the reaction of C9 diazonium tetrafluoroborate tetracycline salts with organotin reagents under modified Stille coupling conditions. Several of these unreported derivatives show promising in vitro biological activity against tetracycline resistant and antibiotic resistant bacteria.