Implantable anti-angiogenic scaffolds for treatment of neovascular ocular pathologies

Abstract

The retinal physiology can accrue oxidative damage and inflammatory insults due to age and metabolic irregularities. Two notable diseases that involve retinal and choroidal neovascularization are proliferative diabetic retinopathy and wet age-related macular degeneration. Currently, these diseases are mainly treated with anti-VEGF drugs (VEGF = vascular endothelial growth factor), generally on a monthly dosage scheme. We discuss recent developments for the treatment of these diseases, including bioactive tissue-engineered materials, which may reduce frequency of dosage and propose a path forward for improving patient outcomes.

Injectable Peptide Hydrogels Loaded with Murine Embryonic Stem Cells Relieve Ischemia In Vivo after Myocardial Infarction

“…Angiogenic SLan is composed of a self-assembling domain, a glycine spacer, and a mimic of VEGF-A QK: KLTWQELYQLKYKGI) and has previously been extensively characterized for material and ultrastructural properties. ,,− ,, This 15-amino-acid-long peptide mimic, QK, has been utilized in a number of previous studies for therapeutic revascularization in peripheral limb, cranial, ocular, and dental pulp tissues; outperforming the other angiogenic mimic self-assembling peptides and/or whole growth factor delivery in comparative studies. ,,,, Complementarily, the literature , suggests that a cell source and a vascularizing scaffold may synergistically promote ischemic tissue regeneration. To show the robust viability of our approach, we used a murine embryonic stem cells (mESCs) line (a generous gift from Dr. Yibing Qyang at Yale University), and we both synthesized and contract-manufactured the angiogenic peptide containing the QK sequence (SLan: K­(SL) 6 K-G-KLTWQELYQLKYKGI) for these studies.…”

“…All scaffolds showed high G ′ at low strain (1%) and inversion with G ″ at high strain (100%). Scaffolds recovered ∼90–95% of their G ′ within 10 s of high strain relief, suggesting that these scaffolds can rapidly assemble into gels in situ after needle (high shear) delivery (Figure B–E). ,− ,− ,,− A notable feature worth exploring, subsequent to loading aqueous solution peptide hydrogel scaffolds with cells, is whether the cells interfere with the shear thinning or recovery process. To evaluate this aspect, we utilized the therapeutic dosing of mESCs used herein (1 M cells/mL) (Figure F) and loaded a mouse myoblast cell line (due to availability, cost, and species relevance) over 3 orders of magnitude (0.1, 1, and 10 M cells/mL).…”

iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel

“…Including the VEGF-motif in the hydrogel monomer sequence is a promising strategy [ [26] , [27] , [28] ]. Further work from our group has shown the facile modifiability of this platform to promote DPSC proliferation, neurogenesis, inflammation modulation, and others [ [76] , [77] , [78] , [79] ]. Recently, stromal cell-derived factor 1 alpha (SDF-1α) was shown to enhance angiogenesis remarkably when overexpressed together with VEGF in DPSCs [ 80 ].…”

Exploration: Nanoparticles in the Diagnosis and Treatment of Retinal Diseases

“…The broad category of retinal neovascularization includes diabetic retinopathy (DR), retinal vascular obstruction (RVO), exudative agerelated macular degeneration (AMD), and even choroidal neovascularization (CNV) [38]. The aberrant angiogenesis that results in bleeding and exudation in the retina or subretina is a common hallmark of these conditions [39]. When it comes to neovascular diseases, it is inevitable to discuss vascular endothelial growth factor (VEGF).…”