# Nanostructured Hydrogel Surfaces for Artificial Extracellular Matrix

> **NIH NIH R21** · PURDUE UNIVERSITY · 2022 · $183,990

## Abstract

PROJECT SUMMARY
Scaffolded stem cell transplantation has the potential to provide structured chemical and mechanical cues to
guide cell growth into functional tissues for regenerative medicine. However, significant challenges have limited
the clinical success of this approach. Cells implanted in large scaffolds often have limited viability due to
hypoxic conditions in the host, while cells injected individually or in small clusters often suffer from poor
retention at the site of injury. Hydrogels are commonly utilized as stem cell scaffold materials because they
confer substantial flexibility in terms of chemical composition and ligand integration. However, hydrogels are
also typically amorphous, limiting control over ligand presentation (important for adhesion and signaling), and
lacking structural cues such as fibers that are present in biological ECM, which impacts mechanical strength.
We have recently demonstrated that it is possible to generate stable, 1-nm-resolution functional patterns on
amorphous polyacrylamide and polydimethylsiloxane surfaces, using sub-nm-thick films of highly ordered
polydiacetylenes (PDAs) that are preassembled and covalently transferred to the hydrogel surface. Our
approach potentially addresses both chemical and mechanical challenges associated with hydrogel stem cell
scaffolds, enabling generation of cell-instructive hydrogel tapes that can be shaped to create 3D scaffolds.
However, to be useful in clinical settings, this strategy will need to be validated with: (1) commonly used
hydrogel stem cell scaffold materials, (2) hydrogel moduli matching the range commonly associated with
tissues, and (3) films thin enough for adequate perfusion to prevent hypoxia and enable normal secretome
interactions. Here, we develop a platform technology based on cell-instructive hydrogel tapes, benchmarking
their chemical and mechanical properties, and their impacts on human mesenchymal stem cells (hMSCs).
In Aim 1, we evaluate the hypothesis that PDA surface functionalization can improve chemical control over
surfaces of hydrogels common in regenerative medicine, orienting and spatially clustering ligand presentation,
to modify stem cell growth in a predictable fashion. We test this by culturing hMSCs on surfaces designed to
maintain stemness or to induce specified differentiation behavior (angiogenesis, adipogenesis,
chondrogenesis), benchmarking against common stochastic hydrogel modification strategies.
In Aim 2, we evaluate the hypothesis that our PDA surface-functionalization approach can improve the
mechanical and handling properties of thin, soft hydrogel films, enabling creation of cell-instructive hydrogel
tapes. We generate and test impacts of paired tapes as cell sandwich scaffolds and 3D constructs that provide
structured chemical surfaces and mechanical environments, while maximizing perfusion to and from cells.
Overall, this proposal develops a modular surface functionalization strategy that can be easily integrated...

## Key facts

- **NIH application ID:** 10373590
- **Project number:** 1R21EB031532-01A1
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Shelley Ann Claridge
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $183,990
- **Award type:** 1
- **Project period:** 2022-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373590

## Citation

> US National Institutes of Health, RePORTER application 10373590, Nanostructured Hydrogel Surfaces for Artificial Extracellular Matrix (1R21EB031532-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10373590. Licensed CC0.

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