Engineering therapeutic scaffolds: integrating drug delivery with tissue regeneration

Aug 21, 2025Journal of materials chemistry. B

Designing treatment frameworks that combine medicine release with tissue healing

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

Effective delivery of bioactive agents remains a challenge in tissue engineering due to their short half-lives and uncontrolled release kinetics.

Drug delivery systems embedded within tissue-engineered scaffolds could enhance regenerative outcomes through controlled release of therapeutic agents.
Bioactivated scaffolds may combine structural support with localized drug release to influence cellular behaviors such as growth and tissue production.
Bioactive agents can be classified by function and their incorporation methods can vary pre-, during-, or post-scaffold fabrication.
Key mechanisms of drug loading and release are critically evaluated, but challenges in scalability and regulatory approval persist.
Emerging trends include scaffolds with on-demand drug release and approaches combining biomaterials with stem cells.

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Tissue engineering (TE) has revolutionized regenerative medicine by integrating scaffolds, cells, and bioactive molecules to repair or replace damaged tissues; the core triad of TE are scaffolds, cells, and biochemical signals. Although advances in biomaterials development and scaffold fabrication techniques have led to significant progress in TE, the effective delivery of bioactive agents, such as growth factors (GFs), antibiotics, anti-inflammatories, and small molecules, remains a challenge due to their short half-lives and uncontrolled release kinetics. This study explores the synergistic potential of drug delivery systems (DDS) embedded within tissue-engineered scaffolds, emphasizing their role in enhancing regenerative outcomes through controlled spatiotemporal release of therapeutic agents. This review highlights drug-activated scaffolds as a transformative solution, combining structural support with localized, sustained drug release to modulate cellular behaviours (proliferation, differentiation, ECM production) and mitigate systemic side effects. We classify bioactive agents by function and analyse their incorporation methods, pre-, during-, or post-scaffold fabrication, to achieve precise release profiles tailored to specific tissues. Key mechanisms of drug loading and release are critically evaluated. Despite progress, challenges persist in scalability, regulatory approval, and mimicking natural healing cues. We discuss emerging trends, including innovative scaffolds with on-demand drug release and combinatorial approaches leveraging biomaterials and stem cells. By bridging gaps between DDS and TE, this paradigm promises to overcome limitations of conventional transplants and synthetic implants. Future directions include optimizing bioink formulations for 3D bioprinting, improving bioactive agent stability, and addressing translational barriers for clinical adoption. This comprehensive review underscores the potential of bioactivated scaffolds to redefine regenerative strategies, offering insights into design principles, therapeutic applications, and hurdles for next-generation TE solutions.

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Engineering therapeutic scaffolds: integrating drug delivery with tissue regeneration

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