Purpose
Poly(ethylene glycol) hydrogels have been widely applied as biomaterials, however solely chain end-reactivity of PEG precursors limit the physiochemical properties and diversity of such hydrogels. Conventional PEG hydrogels are not injectable as is essential for use in most ophthalmic applications.
Methods
Injectable, in situ-gelling poly(oligoethylene glycol) methacrylate (POEGMA) hydrogels are designed using hydrazone chemistry. Hydrazide (POxHy) and aldehyde (POxAy) functionalized POEGMA precursors are synthesized from free-radical polymerization of oligo(ethylene glycol) methacrylate monomers of varying ethylene oxide chain length (n), offering flexibility of (i) degree of reactive functionality (y), (ii) incorporation of additional functionalities (anionic, hydrophobic), (iii) polymer architecture (linear, branched), (iv) molecular weight and v) (if desired) lower-critical solution temperature (LCST) (x). Double barrel syringe extrusion rapidly forms hydrogels in situ.
Results
Precursor concentration and/or functionality (y) is varied to prepare hydrogels exhibiting ranges of elastic moduli (0.2 to 8.0 kPa). Hydrogel swelling properties can be controlled by polymer composition. Specifically, POEGMA hydrogels with x=55 and y=30 are transparent (< 90% transmission at λ>400 nm)(Fig.1) and do not swell in physiological buffer, allowing safe back of the eye injection without inducing glaucoma or vision loss. Low protein adsorption and negligible adhesion of 3T3 fibroblasts is observed. In vivo subcutaneous injections in BALB-c mice show mild inflammatory responses at acute (3 days) and chronic time points (28 days). Protein release kinetics (for bovine serum albumin) are controlled by precursor mixing (x=10 and x=100), resulting in minimal burst release and prolonged sustained release (Fig. 2).
Conclusions
The injectability, transparency, tunable mechanics, inert biological response, and protein release capacity of hydrazone cross-linked POEGMA hydrogels makes them attractive for ophthalmic drug delivery and vitreal replacement applications.
Keywords: 561 injection •
764 vitreous substitutes •
608 nanomedicine