Table 1 Smart biomaterial strategies for spatiotemporal regulation of cardiac repair.

From: Spatiotemporal precision interventions for cardiac repair and regenerative therapy

Biomaterial category

Material platform

Injury-associated cue

Therapeutic function/mechanism

Biological context

Primary spatiotemporal role

Stimuli-responsive biomaterials

Reactive oxygen species (ROS)-responsive

ROS; ischemia/reperfusion injury; acute inflammation

Redox-sensitive degradation or intrinsic antioxidant activity enabling targeted cytoprotection

Acute phase; infarct core and early reperfused regions

Early-phase gating: aligns intervention with transient oxidative stress to preserve cardiomyocyte viability

 

pH-responsive

Local acidosis due to hypoxia and altered metabolism

Protonation-dependent destabilization or acid-labile release of sustained therapeutic cues

Inflammatory to early proliferative phases; infarct core and border zone

Sustained regional engagement: maintains responsiveness across extended injury territories

 

Matrix metalloproteinase (MMP)-responsive

MMP activity during extracellular matrix (ECM) remodeling

Protease-cleavable motifs enabling phase-selective activation and matrix-coupled delivery

Proliferative to remodeling phases; regions of active ECM turnover

Phase-selective access: targets remodeling niches while sparing mature scar tissue

Biomimetic and biointeractive materials

Decellularized ECM (dECM)

Native biochemical cues (ECM proteins, proteoglycans, GAGs)

Preservation of tissue-specific signaling that supports immune modulation and cellular plasticity

Peri-infarct border zone; reparative niche

Instructive scaffold: recapitulates developmental-like signaling environments

 

Synthetic ECM mimetics (for example, gelatin methacryloyl, polyethylene glycol, hyaluronic acid)

Altered tissue mechanics and wall stress

Tunable stiffness, degradation, and ligand presentation to modulate mechanotransduction

Evolving mechanical landscape during remodeling

Modular support: indirectly shapes remodeling trajectories by regulating mechanosensing

 

Conductive/biointeractive materials

Electromechanical uncoupling in fibrotic myocardium

Restoration of electrical conductivity and mechanoelectrical synchrony

Fibrotic and arrhythmogenic regions

Active regulation: integrates electrical and mechanical repair with local delivery

Programmable and sequential delivery

Hierarchical release systems

Overlapping biological phase transitions

Multicargo, staged release matched to inflammatory, proliferative, and remodeling phases

Whole infarct life cycle

Coordinated phase control: enables temporally ordered therapeutic engagement

 

Integrated multimodal platforms

Combined biochemical and mechanical cues

Coupling stimuli-responsiveness with biomimetic matrices for context-aware release

Dynamic post-infarction microenvironment

Synchronized modulation: moves beyond single-event intervention toward system-level control

  1. This table summarizes major classes of smart biomaterials used to achieve spatially and temporally controlled therapeutic engagement after myocardial infarction. Strategies are organized according to their dominant injury-associated cues, material platforms, and mechanisms of action, alongside the biological contexts in which they operate and their primary spatiotemporal roles during post-infarction healing. These approaches illustrate how endogenous signals, matrix interactions, and programmable release architectures can be leveraged to align therapeutic activity with phase-specific and region-specific demands of myocardial repair. GAG glycosaminoglycans.
Back to article page