What question did this study set out to answer?

The aim is to create a hydrogel that can control inflammation while promoting tendon regeneration through IGF-1R/AKT signaling.

May 11, 2026Open Access

An intelligent nano-engineered PLGA@IGF-1 hydrogel for programmed immune modulation and tendon regeneration via IGF-1R/AKT signaling

Key Points

The aim is to create a hydrogel that can control inflammation while promoting tendon regeneration through IGF-1R/AKT signaling.
Developed a nano-hydrogel (CAPP@IGF-1) using phenylborate ester crosslinking and IGF-1-loaded PLGA microspheres.
Evaluated hydrogel’s mechanical properties and self-healing behavior under dynamic conditions in a tendon repair model.
Assessed immune modulation and tendon regeneration in a rabbit tendon injury model for functional outcomes.
CAPP@IGF-1 significantly reduced peritendinous adhesion and improved mechanical recovery of repaired tendons.
Promoted macrophage transition from pro-inflammatory M1 to pro-reparative M2 state (p<0.05).
Enhanced collagen deposition and extracellular matrix remodeling compared to controls.

Abstract

Tendon repair remains a major clinical challenge, largely because current strategies often fail to simultaneously achieve early inflammatory control and subsequent matrix remodeling. To address this problem, we developed a dynamically responsive nano-hydrogel, CAPP@IGF-1, composed of 3-carboxyphenylboronic acid-modified chitosan, polyvinyl alcohol, and IGF-1-loaded PLGA microspheres, which were integrated through phenylborate ester crosslinking. The hydrogel exhibited favorable self-healing behavior together with enhanced mechanical properties, with an elastic modulus of 4.5 MPa and a toughness of 15.3 MJ/m³, enabling it to maintain local structural stability under the complex dynamic conditions of tendon repair. Under the acidic inflammatory microenvironment, CAPP@IGF-1 enabled controlled local release of IGF-1 and activated the IGF-1R/AKT signaling pathway, thereby markedly promoting macrophage reprogramming from the pro-inflammatory M1 state to the pro-reparative M2 state. This was accompanied by suppression of IL-6, IL-2, and TNF-α and upregulation of IL-10, leading to the establishment of a local immune microenvironment favorable for repair. On this basis, the hydrogel further promoted tendon stem/progenitor cell migration, proliferation, extracellular matrix remodeling, and more ordered collagen deposition. In a rabbit tendon injury model, CAPP@IGF-1 notably reduced peritendinous adhesion, and enhanced the mechanical recovery of repaired tendons. Collectively, CAPP@IGF-1 achieves stage-specific intervention during tendon healing through the combined effects of a dynamically crosslinked network, enhanced mechanical properties, and intelligent IGF-1 release. This study demonstrates the feasibility of using materials design to connect inflammatory microenvironment regulation with tissue regeneration and provides a new strategic basis for the precise repair of complex tendon injuries.

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Cite This Study

Yan et al. (Sat,) studied this question.

synapsesocial.com/papers/6a0171ed3a9f334c28271f2e https://doi.org/https://doi.org/10.1186/s12951-026-04493-0

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