Self-Assembly of an Antiangiogenic Nanofibrous Peptide Hydrogel

Abstract

Pathological neovascularization may cause or worsen intraocular posterior segment diseases such as diabetic retinopathy. Prevention of aberrant vascularization is thus an important clinical target. Therapeutic antiangiogenic agents are generally used in diffusible monomeric formulation (e.g., injection of anti-VEGF monoclonal antibodies into the vitreous humor). Here, we report the attachment of a therapeutic antiangiogenic motif to a fibrillizing peptide backbone that undergoes nanofibrous self-assembly into an injectable hydrogel. The peptide can persist for extended periods in a target site, prolonging the therapeutic time frame. The injectability of the hydrogel was investigated through rheometric characterization. Biophysical characterization was complemented by in vitro assays to test the antiangiogenic capability of the scaffold. We also tested persistence and biocompatibility of the hydrogel through in vivo implantation. This injectable hydrogel therapy may unlock potential clinical routes for treating neovascular diseases.

A 3D Bioprinted Material That Recapitulates the Perivascular Bone Marrow Structure for Sustained Hematopoietic and Cancer Models

“…Their composition have the ability to control shape fidelity and shear thinning when incorporated in bioinks [ 70 ]. In designing the composition reported in this report, we incorporated technical outcome with respect to mechanical and functional properties of hydrogels with injectability [ 47 , 48 , 49 ]. Thus, we report on the method used to develop a scaffold with MC and alginate.…”

“…Although hydrogels are often used to mimic soft tissues, it is challenging to bioprint self-supporting mechanically stable hydrogels with an elastic modulus below 1 kPa [ 45 , 46 ]. Technical considerations related to mechanical and functional properties of hydrogels, including but not limited to injectability and permeability, can be critical to the development of bioinks as well as hydrogels for clinical injectables and other applications [ 47 , 48 , 49 ]. Shear thinning and recovery allow materials to be injected to an in vivo or in vitro destination and restore their structure, enabling improved retention of encapsulated factors (e.g., drugs, signaling molecules, cells) upon injection.…”

Design of Bio-Conjugated Hydrogels for Regenerative Medicine Applications: From Polymer Scaffold to Biomolecule Choice

“…Thus, instead of promoting cell growth and regeneration, mAB are used to actively deplete the growth of a tissue, for instance to fight the formation of excessive blood vessels in the retina, which leads to eyesight loss. These mAB were encoded within in a synthetic self-assembled peptide gel, and depending on the amount of gel present, the degree of vascularization could be inhibited accordingly ( Figure 7 ) [ 257 ].…”

“… Histology of a self-assembled peptide hydrogel with mMA encoded within after 3 days ( A , C ) and after 7 days ( B , D ). ( C ) and ( D ) show close to no cellular growth within the gel matrix [ 257 ]. …”

Challenges in Translating from Bench to Bed-Side: Pro-Angiogenic Peptides for Ischemia Treatment

“…A number of strategies have been investigated for the presentation of VEGF signaling in scaffolds; self-assembling peptide hydrogels presenting high density of epitopes mimicking VEGF and other growth factors have been developed [37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61]. Using mimics of VEGF, large macromolecules can be functionalized.…”