title: Design and application of bio-absorbable scaffolds for tissue-engineering and retinal degeneration therapeutics
Creators: name: Behtaj, Sanaz
Publisher: name: Griffith University
Year: 2021
Subjects: subject: Glaucoma
subject: retinal ganglion cells
subject: RGC
subject: stem cell-based RGC replacement therapy
subject: tissue-engineered scaffolds
subject: materials

description: Glaucoma, a characteristic type of optic nerve degeneration in the posterior pole of the eye, is a common cause of irreversible vision loss and the second leading cause of blindness worldwide. As an optic neuropathy, glaucoma is identified by increasing degeneration of retinal ganglion cells (RGCs), with consequential vision loss. Current treatments only postpone the development of retinal degeneration, and there are as yet no treatments available for this disability. Recent findings in ocular regeneration have opened promising avenues to apply stem cell-based modalities to restore vision in progressive optic neuropathies. As such, the stem cell-based RGC replacement therapy, as a promising treatment of glaucoma, could be facilitated by using tissue-engineered scaffolds that provide a supportive structure. An appropriate selection of materials is a fundamental consideration in fabricating these scaffolds. My study investigates the structure, composition and properties of three most commonly used biopolymer materials blended with [polycaprolactone] (PCL) at 2:1 (wt.%) ratio, namely, poly(glycerol sebacate) (PGS)/PCL, polylactic-co-glycolic acid (PLGA)/PCL, poly-l-lactide (PLLA)/PCL and pure PCL as carrier vehicles for human embryonic stem cell derived retinal progenitor cell (hESC-RPC) attachment and proliferation. The physicochemical properties of PGS/PCL, PLLA/PCL, PLGA/PCL and pure PCL fibrous scaffolds, fabricated under the identical electrospinning conditions, were analysed employing scanning electron microscopy, contact angle analysis, Raman spectroscopy, electrical and ionic conductivity measurements, and supplemented by an in-vitro hESC-RPC adhesion and proliferation studies. My findings have shown that PGS/PCL scaffolds promote hESC-RPC attachment and growth more favourably compared to other polymeric blends and pure PCL, owing to a combination of advantageous surface and bulk properties, overall demonstrating a potential for PGS/PCL blend to become a suitable vehicle for hESC-RPC delivery in a possible future clinical therapy for the treatment of retinal degenerative disorders. Also, the study investigated a mean to differentiate hESC-RPCs into RGCs and developed a novel and a straightforward approach for hESC-RPC-to-RGC differentiation on PCL/PGS fibrous scaffolds, which displayed the most advantageous properties for hESC-RPC attachment and proliferation. My results revealed that PCL/PGS scaffolds have indeed effectively promoted the differentiation of hESC-RPCs into RGCs and supported the orientated elongation of RGCs' neurites, further validating the PGS/PCL scaffold as an appropriate supportive vehicle for RGC proliferation. We trust that my study aids to the knowledge on the selection of biomaterials according to their physicochemical properties and structural characteristics for hESC-RPC cultivation and also provides valuable practical knowledge on the application of the tissue-engineered biomaterial structures for RGC cultivation as a part of clinical therapy in possible future successful treatments of glaucoma.