2025-11-04 マサチューセッツ工科大学(MIT)
<関連情報>
- https://news.mit.edu/2025/new-patch-could-help-heal-heart-1104
- https://www.cell.com/cell-biomaterials/fulltext/S3050-5623(25)00240-5
TIMED: 微粒子カプセル化と送達による時間的介入 – 心筋梗塞後治療のためのプログラム放出システム TIMED: Temporal intervention with microparticle encapsulation and delivery—A programmed release system for post-myocardial infarction therapy
Erika Yan Wang ∙ Elizabeth A. Calle ∙ Binbin Ying ∙ … ∙ Yi Liu ∙ Robert Langer ∙ Ana Jaklenec
Cell Biomaterials Published:November 4, 2025
DOI:https://doi.org/10.1016/j.celbio.2025.100249
The bigger picture
Myocardial infarction (MI) remains one of the most pressing global health problems, leaving millions of patients with long-term cardiac dysfunction despite advances in acute surgical care. A major challenge is that the biological response to MI unfolds in distinct phases, yet most current therapies deliver drugs in a single burst, poorly aligned with these dynamic needs. This work introduces TIMED (temporal intervention with microparticle encapsulation and delivery), an implantable polymeric system. By combining spatially patterned microparticles within a hydrogel patch, TIMED achieves a programmable multi-phasic release profile. The system demonstrated strong mechanical performance and biocompatibility for surgical handling and long-term implantation and maintained stability during storage, showing potential for off-the-shelf clinical use.
First validated in human stem cell-derived cardiac tissues, our sequential treatment regimen delivered by TIMED enhanced survival and vascularization, while limiting fibrosis and supporting the biological logic of timed dosing. In a rodent MI model, TIMED treatment improved survival, reduced cardiac injury markers and infarct size, and restored heart function beyond what was achieved with equivalent dosing delivered by conventional intravenous therapy. These findings establish the first cardiac implantable polymeric platform with a programmable release profile, enabling advanced multi-dosing localized therapy. Beyond the demonstrated treatment regimen, the TIMED platform’s precise control over drug combinations and release timing provides a framework for sequential treatment across broad therapeutic contexts.
Highlights
- Programmable multi-phasic release via microparticles in a hydrogel patch
- Strong mechanics, biocompatibility, and storage stability for clinical use
- TIMED improves survival, restores function, and reduces injury in vitro and in vivo
- Modular, localized sequential therapy adaptable to broad clinical contexts
Summary
Myocardial infarction (MI) is a major global health challenge. Surgical interventions address the acute phase but often fail to support long-term recovery. Sequential post-operative drug delivery offers promise but is constrained by release methods. Here, we developed TIMED (temporal intervention with microparticle encapsulation and delivery), a polymeric device enabling programmed sequential release through spatially patterned microparticles in a tough hydrogel matrix. TIMED demonstrated excellent mechanical performance and biocompatibility for long-term implantation and retained strong stability after storage. A sequential dosing regimen aligned with the innate post-MI response was first validated in hiPSC-derived cardiac tissues, where it enhanced cell viability and vascularization while reducing collagen deposition. In vivo, delivery via the TIMED improved survival, reduced injury markers and infarct size, and enhanced cardiac output, outperforming equivalent i.v. dosing. This work establishes a first-of-its-kind cardiac implantable polymeric platform with modular sequential release and provides a framework for programmed multi-dosing across diverse applications.
