Cell-Laden Supramolecular And Covalent Polymer Hydrogels For High-Shear Delivery: A Design Of Experiments Approach

Document Type

Article

Publication Date

3-10-2026

School

Polymer Science and Engineering

Abstract

Effective design of cell-delivery scaffolds is of key importance for regenerative medicine technologies to meet their full potential, especially when considering cell delivery to wounds of complex architecture or directly into the biological environment. Few studies, however, focus on a systematic approach to understanding the cell, polymer scaffold, and final biomaterial properties of this composite material. In this work, we report on the systematic analysis of a supramolecular hydrogel composed of ionically cross-linked peptide amphiphile (PA) nanofibers, optimized for high-shear delivery of therapeutic cells, and compare the performance of this biomaterial to a covalent polymer hydrogel of ionically cross-linked alginate. Using a full factorial design of experiments (DoE), we investigated the interplay between polymer concentration and cell loading to determine the impact on mechanical properties, structural integrity, substrate adhesion, and sprayability of the hydrogel. The shear-thinning and thixotropic nature of the supramolecular hydrogels enabled effective deposition through a spray nozzle, not possible with the alginate hydrogel, while preserving cell viability and hydrogel mechanical properties. The supramolecular backbone of the PA nanofibers enabled remarkable mechanical resilience and full recovery post-spray, even at cell loadings as high as 2 million cells/mL, while significant loss of gel integrity was observed with the alginate hydrogel at equivalent cell loadings. Our findings establish a robust structure–property relationship framework for the formulation of cell-laden supramolecular hydrogels capable of high-shear delivery, highlighting their potential as customizable platforms for regenerative medicine, advanced wound care, and 3D printing applications.

Publication Title

Chemistry of Materials

Volume

38

Issue

5

First Page

2357

Last Page

2371

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