Defined Polymer–Peptide Conjugates to Form Cell‐Instructive starPEG–Heparin Matrices In Situ

Abstract

Poly(ethylene glycol)-peptide- and glycosaminoglycan-peptide conjugates obtained by a regio-selective amino acid protection strategy are converted into cell-instructive hydrogel matrices capable of inducing morphogenesis in embedded human vascular endothelial cells and dorsal root ganglia.

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

“…[128][129][130][131] Maleimides are typically incorporated into polymer chains via carbodiimide-mediated reactions of polymer-bound acid groups with nucleophilic maleimide precursors or by nucleophlic attack of polymer-bound amines to N -hydroxysuccinimide activated esters functionalized with maleimide groups, such as succinimidyl 4-( N -maleimidomethyl)cyclohexane-1-carboxylate (SMCC). [ 132 ] Thiol-maleimide cross-linking offers the advantage of increased speed of reaction over acrylates and methacrylates; [ 131 ] furthermore, maleimides do not readily undergo free radical polymerizations, which increases the simplicity of the synthetic steps required to generated maleimide-functionalized polymers.…”

Neurotropic growth factors and glycosaminoglycan based matrices to induce dopaminergic tissue formation

“…Building on the options of a recently introduced PEGglycosaminoglycan matrix platform [33] this study aimed at exploring specific triggers for the engineering of dopaminergic tissue suitable for the future reconstruction of the nigro-striatal dopaminergic pathway in PD patients. Material parameters of biohybrid PEG-glycosaminoglycan gels (storage modulus of G 0 z2e2.5 kPa and a RGD density of 2 mol RGD/mol heparin) which were previously identified to support adhesion, survival and maturation of murine midbrain progenitor neural cells were used as a starting point for the further functionalization of the matrices with selected neurotropic factors [32].…”

“…For that purpose, we have recently reported a biohybrid hydrogel platform based on covalently cross-linked heparin and star-shaped poly(ethylene glycols) (star-PEG) in which network characteristics can be gradually varied while heparin contents remain constant [32,33]. The materials were shown to allow for the tailored covalent attachment of cell adhesion mediating peptides and the reversible, non-covalent binding of growth factors in ways resembling the presentation of factors in naturally occurring extracellular matrices.…”

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

“…Semi-synthetic biomaterial scaffolds can be produced by combining these natural biopolymers with synthetic polymers such as PEG, with the aim of representing or mimicking host tissue more closely [53,54], allowing cellular attachment [24], introducing enzyme cleavability [55], or improving the binding of growth factors [56]. These semi-synthetic materials are often designed in such a way that a functionalized PEG molecule (often branched) is used to crosslink the biopolymer either via an intrinsically present amine [57], via EDC/NHS activated carboxyl groups [58], or via a previously added functional group [59].…”

“…A group with much experience in star-PEG-heparin biomaterials has recently shown a versatile approach to incorporate two peptides (one MMP cleavable, and one laminin-derived adhesion peptide) into a hydrogel structure [59]. Prior functionalization of maleimide terminated star-PEG firstly with a cell adhesion peptide (Seq: SIKVAVGWCG), then a MMP cleavable domain with a protected second cysteine group (Seq: GCGGPQGIWGQGGCG) allows a peptide functionalized molecule that can crosslink maleimide functionalized heparin in situ via Michael addition (cysteine to maleimide) (see Fig.…”