# 3D Printed Engineered Living Materials for Drug Delivery

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2022 · $225,936

## Abstract

PROJECT SUMMARY
Traditional drug delivery platforms are limited by the amount of drug that can be loaded into the delivery system.
While drug loading capacity can reach 50% by weight for some polymeric systems, the time period over which
the delivery of the therapeutic can be sustained is often limited. In addition, the therapeutic efficacy of a local
drug delivery system is related to the local bioavailability of the active agent. Devices that bio-catalytically
produce the therapeutic in situ could thus provide more effective local delivery of the active drug and improve
therapeutic efficacy. The long-term vision for this program is to create the next-generation 3D printed in situ drug
production and delivery devices, including drug-eluting stents, microneedles, and patches, based on engineered
living materials (ELMs) for localized and sustained therapeutic delivery. ELMs are composites of microorganisms
incorporated within a polymeric matrix, wherein the cells maintain their viability and can be metabolically
engineered to produce a therapeutic compound. Despite the immense potential of ELMs for drug delivery
applications, the primary challenges to the deployment of ELMs as drug-eluting stents or patches to treat
intestinal diseases are that ELMs must (i) be processable into precise form factors (e.g., patient-specific stents)
with the requisite mechanical properties, (ii) biodegrade into non-cytotoxic components at predetermined rates,
and (iii) bio-catalytically produce and elute the therapeutic agent in situ for the lifetime of the device. The objective
of this proposal is to develop 3D printable resins that afford biodegradable hydrogel constructs with a tunable
stiffness, and to demonstrate the fabrication of a prototype ELM device for sustained delivery of a model
compound. In Aim 1, we will create aqueous resins with non-pathogenic E. coli Nissle 1917 (EcN) that can be
3D printed into hydrogel constructs using a commercially available 3D printer. We will formulate aqueous resins
comprised of soluble globular protein derivatives that can be co-polymerized with water-soluble acrylate
monomers upon photo-initiated polymerization. The mechanical properties of the ELM hydrogels (stiffness,
strength, and toughness) and rates of enzymatic degradation will be quantified for each resin formulation. In Aim
2, we will metabolically engineer non-pathogenic EcN to produce berberine as a model therapeutic compound.
We will further evaluate the cytotoxicity and epithelial integrity of Caco-2 cells in the presence of 3D printed
ELMs. As validation of these ELMs we will use an in vitro model to confirm the production and elution of berberine
from the 3D printed ELM by evaluating the Caco-2 response to proinflammatory stimulation. We envision these
3D printed ELMs to be used as devices for local drug delivery in the treatment of malignancies or inflammatory
diseases affecting the intestines. While our ELM platform is compatible with a broad array of micro...

## Key facts

- **NIH application ID:** 10370976
- **Project number:** 1R21EB031256-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Alshakim Nelson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $225,936
- **Award type:** 1
- **Project period:** 2022-04-05 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370976

## Citation

> US National Institutes of Health, RePORTER application 10370976, 3D Printed Engineered Living Materials for Drug Delivery (1R21EB031256-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10370976. Licensed CC0.

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