# Tunable Mechano-Activated Microcapsules for Therapeutic Delivery

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $342,781

## Abstract

Abstract
This project seeks to advance controlled drug delivery systems via the development of novel mechanically
activated microcapsules (MAMCs) for therapeutic delivery in response to mechanical load. While previous
strategies have established microcapsules with various triggered release mechanisms (e.g., pH, heat, osmotic
swelling) for drug delivery, most require external actuation, and physiological feedback plays little role in
release. This proposal takes the unique approach of using mechanically loaded environments (e.g., articulating
joints) to trigger and control release of therapeutics. Upon rupture, bioactive molecules released from
microcapsules (embedded within matrices), can stimulate anabolic processes leading to cell proliferation,
differentiation, matrix biosynthesis, or a host of other responses including control of inflammation. Given that
the timing of release is controlled by mechanical load, it is possible to tune the release of factors based on the
mechano-sensitivity of the microcapsules. For example, these MAMCs may be used in conjunction with
engineered tissues to foster regeneration under controlled loading during rehabilitation, or designed to actuate
in response to normal walking and exercise, so as to promote rapid local repair. In Aim 1 we will investigate
the structure-release properties of the MAMCs under physiologic loading scenarios by modifying key
fabrication parameters, including polymer composition, shell thickness-to-radius ratio, and shell
elasticity/plasticity. In Aim 2 we will characterize failure properties of MAMCs embedded in engineered
matrices analogous to native tissue as a function of fabrication parameters, adhesion to local environment, and
load. In Aim 3 we will evaluate the effect of therapeutic release from MAMCs embedded within engineered
cartilage for the purpose of stimulating growth in response to physiologic loading and promoting repair in
response to injurious loading. Finally, in Aim 4, we will assess the actuation of MAMCs in an in vivo load
bearing animal model of cartilage repair. Collectively these Aims will test the hypothesis that physiologically
relevant mechanical forces can temporally and spatially control the delivery of bioactive growth promoting
molecules that positively impact tissue formation and repair. Completion of these Aims will culminate with
validation of MAMCs in a clinically relevant animal model and support this as a novel drug delivery system with
broad applications in directing regeneration and repair in mechanically loaded tissues.

## Key facts

- **NIH application ID:** 10017663
- **Project number:** 5R01AR071340-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** George R. Dodge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,781
- **Award type:** 5
- **Project period:** 2017-09-21 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017663

## Citation

> US National Institutes of Health, RePORTER application 10017663, Tunable Mechano-Activated Microcapsules for Therapeutic Delivery (5R01AR071340-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017663. Licensed CC0.

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