Self-assembly of trifunctional tripeptides to form neural scaffolds

Abstract

Peptide self-assembly has been exploited to generate a multitude of biomaterials that exhibit biocompatibility due to their similarity to naturally occurring proteins. Previously, we have shown β-tripeptides self-assemble despite containing...

Esterase-Mediated Sustained Release of Peptide-Based Therapeutics from a Self-Assembled Injectable Hydrogel

“…Depolarization induced an increase in cytoplasmic calcium in DRG neurons treated with either BDNF mimetics or NGF (Figure G–I). Similarly, glial cells exposed to these treatments responded strongly to ATP . Calcium mobilization was not seen in either cell type incubated with the inert hydrogel or medium alone (Figure F,J), indicating that the sustained release of BDNF mimetics was responsible for the survival of functional neurons and satellite glial cells.…”

“…Similarly, glial cells exposed to these treatments responded strongly to ATP. 39 Calcium mobilization was not seen in either cell type incubated with the inert hydrogel or medium alone (Figure 6F,J), indicating that the sustained release of BDNF mimetics was responsible for the survival of functional neurons and satellite glial cells. These increases were quantified and demonstrate neuron and glial viability and the efficacy of the hydrogel-delivered peptide therapeutics (Figure 7).…”

“…To synthesize the prerequisite β 3 -amino acid, the backbone acid of ( R )- N -Fmoc α-aspartic acid β- tert -butyl ester was converted to propargyl ester 1 , followed by the cleavage of tert -butyl ester from the side chain to afford ( R )- N -Fmoc α-aspartic acid propargyl ester β-carboxylic acid 2 . N -Acetyl α-aspartic acid was similarly appended with an (Fmoc)­aminoethylamide spacer to give the N -acetyl α-aspartic acid (Fmoc)­aminoethylamide β-carboxylic acid, as previously synthesized, which was then introduced as the N-terminal β 3 -amino acid residue via solid-phase peptide synthesis for subsequent lipidation of the β 3 -tripeptide. The versatility, orthogonality, and chemoselectivity of copper-catalyzed click chemistry have been well documented for the ligation of small molecules, oligonucleotides, and peptide cargos to complex peptides via a convergent synthetic strategy. − This method was thus utilized to conjugate the azido derivatives of BDNF mimetics or lactose azide with the alkyne-linked derivative of lipidated β 3 -tripeptide 3 to afford the bioconjugates of lipidated β 3 -tripeptide 4–6 (Scheme ).…”

A comparison of fixation methods for SEM analysis of self-assembling peptide hydrogel nanoarchitecture

“…The optimisation of hydrogel nanoarchitecture, and specifically porosity, is critical due to the influence of these properties on cell biology, delivery of cell cargo such as exosomes, degradation, and cellular infiltration. [7][8][9] Previously we reported self-assembling β-peptide hydrogels for therapeutic molecule delivery and regenerative medicine, [10][11][12][13] and subsequently we aimed to control hydrogel nanoarchitecture to optimise this function. While scanning electron microscopy (SEM) is a widely used method to study hydrogel nanoarchitecture, it is well-established that the sample preparation methods required for SEM can alter the structure of hydrogels, 14,15 due to the difficulty in freezing or removing the water without disturbing the delicate structures.…”

Photothermal Sensitive 3D Printed Biodegradable Polyester Scaffolds with Polydopamine Coating for Bone Tissue Engineering

“…Developing a type of bone scaffold with excellent osteoinductivity and programmable pore structure is the current research focus [ 4 ]. Several advanced and efficient manufacturing methods are used to manufacture porous biomaterials, such as self-assembly [ 5 , 6 ] and electrospinning [ 7 ]. However, most methods for obtaining scaffolds suffer from disadvantages such as poor pore structure and interconnectivity, long subsequent processing steps, and difficulty in rapidly preparing patient-specific scaffolds [ 8 , 9 , 10 ].…”