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Microengineering 3D Collagen Hydrogels with Long-Range Fiber Alignment
Published on: September 7, 2022
Tunable hydrogel-microsphere composites that modulate local inflammation and collagen bulking
Elena Tous1, Heather M Weber, Myung Han Lee
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Acta Biomaterialia
|June 5, 2012
Summary
This study developed a tunable hyaluronic acid (HA) and poly(lactide-co-glycolide) (PLGA) microsphere composite for tissue bulking. The injectable biomaterial system demonstrated potential in cardiac applications by limiting adverse remodeling after infarction.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Injectable biomaterials can modulate local tissue responses, influencing inflammation and matrix production.
- Existing volumizing agents, like dermal fillers, stimulate collagen production.
- There is a need for versatile biomaterial systems with tunable properties for diverse tissue applications.
Purpose of the Study:
- To formulate and assess a tunable composite system of hyaluronic acid (HA) hydrogels and poly(lactide-co-glycolide) (PLGA) microspheres.
- To investigate the impact of hydrogel degradation rate and microsphere concentration on tissue interactions.
- To evaluate the efficacy of this composite system for cardiac tissue bulking and post-infarction stabilization.
Main Methods:
- Developed injectable, degradable hydrogels using HA functionalized with hydroxyethyl methacrylate (HeMA).
- Incorporated PLGA microspheres (~50 μm diameter) into the HA hydrogels, varying degradation (20 or 70 days) and microsphere content (0-300 mg/mL).
- Assessed subcutaneous tissue responses and cardiac tissue bulking in a sheep model of myocardial infarction.
Main Results:
- In subcutaneous implants, faster HA hydrogel degradation and higher PLGA microsphere concentrations (e.g., 75 mg/mL) promoted increased cellular interactions and macrophage response.
- In infarcted ovine hearts, fast-degrading HeMA-HA hydrogels with 75 mg/mL microspheres limited left ventricular dilation.
- These cardiac injections increased myocardial wall thickness (~35%) and vascularization (~60%) in the infarct zone, reducing adverse remodeling compared to controls.
Conclusions:
- Material design is crucial for expanding the applications of tissue bulking composites.
- The tunable HA-PLGA microsphere system offers potential for various biomedical applications, including cardiac repair.
- This composite system demonstrates promise for modulating tissue response and providing structural support in regenerative medicine.

