Versatile tissue-injectable hydrogels capable of the extended hydrolytic release of bioactive protein therapeutics

Bioeng Transl Med, 2024 · DOI: 10.1002/btm2.10668 · Published: May 1, 2024

Simple Explanation

The study addresses challenges in clinical hydrogels related to inconsistent therapeutic exposure and difficulties in polymer insertion. Injectable, biocompatible hydrogels were engineered as a local therapeutic depot. The hydrogel solutions polymerize in situ in a temperature-sensitive manner, persist in tissue, and facilitate the delivery of bioactive therapeutics in subsurface locations.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Anti-CD47 monoclonal antibodies incorporated into subsurface-injected hydrogel solutions exhibited cytotoxic activity against infiltrative high-grade glioma xenografts in the rodent brain.
2
Hydrogel-generated gradients of murine CXCL10 resulted in significant recruitment of CD8+ T-cells and the attenuation of tumor growth in a “cold” syngeneic melanoma model.
3
This study highlights a highly customizable, hydrogel-based delivery system for local protein therapeutic administration to meet diverse clinical needs.

Research Summary

The study developed injectable hydrogels for local, controlled release of protein therapeutics into tissue. The hydrogel, featuring slowly hydrolyzing linkers, prolongs the therapeutic effect, minimizing the requirement for repeated surgeries. Designed for subsurface injection, our hydrogel provides a customizable range of release profiles, lasting from days to over a month as needed.

Practical Implications

Targeted Immunotherapy

The hydrogel can deliver potent immunotherapies with severe systemic toxicities directly to the tumor site, reducing systemic side effects.

Extended Therapeutic Effect

Slowly hydrolyzing linkers in the hydrogel prolong the therapeutic effect, reducing the need for repeated surgeries.

Versatile Clinical Solutions

The customizable range of release profiles and compatibility with various proteins provides clinicians with versatile solutions for diverse clinical circumstances.

Study Limitations

1
Foreign body response to the nondegradable hydrogel
2
Potential for immune cell over-activation and cytokine release syndrome with uncontrolled chemokine administration
3
Adjusting the diffusion rate of protein payloads, may only extend release rates on the scale of hours

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