# Cell-Laden Supramolecular and Covalent Polymer Hydrogels for High-Shear Delivery: A Design of Experiments Approach

## TL;DR

This paper introduces a new type of hydrogel that can deliver cells under high-shear conditions, making it useful for regenerative medicine and 3D printing.

## Contribution

A systematic design of experiments approach to optimize supramolecular hydrogels for high-shear cell delivery.

## Key findings

- Supramolecular hydrogels enabled effective high-shear cell delivery while preserving cell viability.
- Supramolecular hydrogels showed mechanical resilience and full recovery post-spray at high cell loadings.
- Alginate hydrogels showed significant loss of integrity at similar cell loadings.

## 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.