Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Tissue Engineering

Background:

• Pharmacological modulation of injury responses requires precise, multi-drug delivery over time.
• The foreign body response to implants is a dynamic process leading to implant failure.

Purpose of the Study:

• To develop and characterize a novel controlled delivery system with three compartments for sequential drug release.
• To demonstrate the system's utility in mitigating the foreign body response to implants.

Main Methods:

• Fabrication of a core-shell electrospun fiber and electrosprayed sphere system for multi-phasic drug release.
• In vitro evaluation of drug releasates on macrophage fusion, nuclear factor-κB (NF-κB) pathway, and fibroblast transforming growth factor-β (TGF-β) signaling.
• In vivo assessment of the drug-eluting constructs' efficacy in reducing macrophage fusion and fibrotic encapsulation.

Main Results:

• The system successfully released drugs sequentially over different timescales.
• In vitro studies confirmed modulation of NF-κB and TGF-β pathways.
• In vivo studies demonstrated dose-dependent reduction in macrophage fusion and fibrotic encapsulation, mitigating foreign body response.

Conclusions:

• The developed multi-compartment controlled delivery system enables spatiotemporal drug release for modulating dynamic biological processes.
• This technology holds potential for improving implant longevity and treating other conditions requiring sequential pharmacological intervention.