Self-Sorting Microscale Compartmentalized Block Copolypeptide Hydrogels

Abstract

Multicomponent interpenetrating network hydrogels possessing enhanced mechanical stiffness compared to their individual components were prepared via physical mixing of diblock copolypeptides that assemble by either hydrophobic association or polyion complexation in aqueous media. Optical microscopy analysis of fluorescent probe labeled multicomponent hydrogels revealed that the diblock copolypeptide components rapidly and spontaneously self-sort to form distinct hydrogel networks that interpenetrate at micron length scales. These materials represent a class of microscale compartmentalized hydrogels composed of degradable, cell-compatible components, which possess rapid self-healing properties and independently tunable domains for downstream applications in biology and additive manufacturing. 1 Hydrogels can display a broad range of structural and functional properties, and are being developed for many applications including as cell scaffolds, depots for therapeutic delivery, contact lenses, and coatings. 1-3 For certain applications, it is desirable to introduce multiple network components into hydrogels to alter mechanical properties or to create distinct functional environments, as can be found in biological materials. 1-4 Examples include covalently crosslinked double network hydrogels possessing remarkable increased strength and toughness compared to their individual single network components, 5,6 as well as multicomponent hydrogels containing orthogonally self-assembled physical networks that can respond differently to various external stimuli, similar to cytoskeletal components found within cells. 7-11 Most of these hydrogels consist of networks that interpenetrate at molecular length scales, and there has been considerable recent effort to develop multicomponent hydrogels capable of possessing microscale compartmentalization akin to that found in cells and biological scaffolds. 12-14 Here, we report that mixtures of diblock copolypeptides are able to rapidly self-sort during assembly to spontaneously give dual compartment (DC) physical hydrogels containing distinct networks that interpenetrate at micrometer length scales. These DC hydrogels also possess significantly increased, and tunable, mechanical properties compared to their individual components (Figure 1).

Synthesis and Evaluation of Cytocompatible Alkyne-Containing Poly(β-amino ester)-Based Hydrogels Functionalized via Click Reaction

“…Polymeric hydrogels are beneficial for biomedical applications, − such as tissue engineering and drug/gene delivery systems, since the hydrolyzed microenvironments provide cells/tissues with adjustable physicochemical properties and structure similar to the extracellular matrix in a swollen state. Hydrogels are generally prepared by cross-linked polymers to form highly interpenetrating networks .…”

Self-sorting assembly of artificial building blocks

“…10a). 92 Polyanion (M O A) 155 E 55 co-assembled with (M O A) 155 K 55 due to the electrostatic attraction and sorted with neutral polymer (M O A) 200 L 30 which aggregated under hydrophobic interactions. The green fluorescent probe was labelled on (M O A) 155 E 55 and red on (M O A) 200 L 30 to observe the sorted hydrogels under CLSM (Fig.…”

Multifunctional Single‐Component Polypeptide Hydrogels: The Gelation Mechanism, Superior Biocompatibility, High Performance Hemostasis, and Scarless Wound Healing

“…[ 8 ] Deming et al. pioneered a novel class of diblock copolypeptide hydrogels with rapid‐recovering, self‐healing, and self‐sorting compartmentalization attributes, [ 9–11 ] which have been used for controlled cell delivery and antimicrobial wound dressings. [ 12–14 ] Thermosensitive polypeptide‐b‐poly(ethylene glycol) (PEG) block copolymers with sol‐gel transitions have been intensively studied for supramolecular hydrogels while they usually gel at high concentrations (>10 wt%) and disassociate into suspensions beyond a transition temperature.…”