Fabrication and evaluation of Maillard reaction crosslinked alginate-albumin scaffolds loaded with fenofibrate for retinal applications

​Retinal diseases including age-related macular degeneration and diabetic retinopathy are the major cause of irreversible blindness. Available treatment options are only effective for managing the early stages of retinal disorders by slowing down the disease progression. Three-dimensional (3D) polymeric scaffolds have recently emerged as promising alternatives to repair retinal degeneration and recover vision. These scaffolds are designed to mimic the native extracellular matrix by providing structural support and promoting cell activities. 3D scaffolds can be also formulated to deliver therapeutic agents to the retina, potentially overcoming current treatment limitations for retinal diseases.

​This thesis reports the fabrication and development of implantable retinal scaffolds crosslinked by the Maillard reaction. Initial experiments examined the occurrence of the Maillard reaction between alginate (ALG) and bovine serum albumin (BSA) in deionised water. The 3D scaffolds, made up of ALG and BSA, were produced using the freeze-drying method. Incorporating BSA into the formulations enhanced the overall porosity of the scaffold due to its foamability, and the Maillard reaction increased the thickness of pore walls, resulting in a stiffer scaffold with Young’s modulus of 13.08 kPa suitable for retinal regeneration.

​The potential use of the scaffolds as a drug delivery system was investigated. Fenofibrate, a neuroprotective agent, was loaded into ALG-based formulations and quantified using HPLC analysis. The presence of BSA in the formulations significantly increased the loading capacity of ALG scaffolds from about 40% to 80%. Compared with ALG and nontreated ALG-BSA scaffolds, ALG-BSA conjugated scaffolds exhibited less swelling in aqueous media and slower release of FNB in a simulated vitreous fluid. Moreover, the ARPE-19 cells cultured on the scaffolds demonstrated that the Maillard reaction enhanced cell viability and cell distribution within 14 days. The results presented in this thesis strongly suggest the potential of the Maillard reaction scaffold for retinal regenerative medicine.