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Recellularization and Integration of Dense Extracellular Matrix by Percolation of Tissue Microparticles
Jeanne E Barthold1, Brittany M Martin1, Shankar Lalitha Sridhar1
1Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO.
Advanced Functional Materials
|November 29, 2021
Summary
We developed "tissue clay," a novel biomaterial from extracellular matrix microparticles and hydrogel, that can be molded for tissue repair. This material supports cell migration and tissue regeneration, showing promise for various tissue engineering applications.
Area of Science:
- Biomaterials Engineering
- Tissue Engineering
- Regenerative Medicine
Background:
- Engineered biomaterials using decellularized extracellular matrix (ECM) are crucial for tissue repair.
- Dense ECM biomaterials often lack formability and hinder cell migration, limiting tissue regeneration.
- There is a need for versatile biomaterials that mimic native tissue architecture and support cellular integration.
Purpose of the Study:
- To develop a novel, formable biomaterial composite for tissue regeneration.
- To investigate the mechanical properties and cellular response of the engineered material.
- To demonstrate the broad applicability of the material for various musculoskeletal and connective tissues.
Main Methods:
- Created a composite material termed "tissue clay" using hyaluronic acid-based hydrogels and acellular articular cartilage microparticles (~125-250 microns).
- Determined a percolation threshold (0.57 v/v) for achieving a compressive modulus >300kPa.
- Assessed chondrocyte recellularization, migration (chemotaxis), gene expression, and in vivo performance in a mouse model.
Main Results:
- Tissue clay demonstrated moldability and crosslinking capabilities, mimicking native tissue architecture.
- A percolation threshold was identified, enabling tunable mechanical properties (compressive modulus >300kPa).
- Primary chondrocytes recellularized particles within 48 hours, showing distributed cellularity and expressing cartilage repair genes. Muscle, skin, and cartilage composites persisted in vivo.
Conclusions:
- The developed tissue clay composite balances mechanical properties with cellular integration and tissue regeneration.
- Material architecture and particle packing are key to achieving desired biomaterial performance.
- This technique offers a versatile platform for engineering various dense musculoskeletal and connective tissues.
