Percolation of Microparticle Matrix Promotes Cell Migration and Integration while Supporting Native Tissue Architecture

Abstract

Cells embedded in the extracellular matrix of tissues play a critical role in maintaining homeostasis while promoting integration and regeneration following damage or disease. Emerging engineered biomaterials utilize decellularized extracellular matrix as a tissue-specific support structure; however, many dense, structured biomaterials unfortunately demonstrate limited formability, fail to promote cell migration, and result in limited tissue repair. Here, we developed a reinforced composite material of densely packed acellular extracellular matrix microparticles in a hydrogel, termed tissue clay, that can be molded and crosslinked to mimic native tissue architecture. We utilized hyaluronic acid-based hydrogels, amorphously packed with acellular articular cartilage tissue particulated to ~125-250 microns in diameter and defined a percolation threshold of 0.57 (v/v) beyond which the compressive modulus exceeded 300kPa. Remarkably, primary chondrocytes recellularized particles within 48 hours, a process driven by chemotaxis, exhibited distributed cellularity in large engineered composites, and expressed genes consistent with native cartilage repair. We additionally demonstrated broad utility of tissue clays through recellularization and persistence of muscle, skin, and cartilage composites in a subcutaneous in vivo mouse model. Our findings suggest optimal strategies and material architectures to balance concurrent demands for large-scale mechanical properties while also supporting integration of dense musculoskeletal and connective tissues.

An update on a technical method of cartilage decellularization: (a physical-based protocol)

“…Finally, the peak at 1003 cm −1 was assigned to phenylalanine, an amino acid that is a component of many proteins. 32,33 These peaks were demonstrated in both groups of tissues. A peak at 548 cm −1 was sharper in intact samples compared to DC samples, which were candidates for cholesterol.…”

Multiscale Computational Framework to Investigate Integrin Mechanosensing and Cell Adhesion

“…Key components that have previously been modeled such as the cell membrane, integrin's transmembrane domain, and integrin clustering and diffusion 28,34,[45][46][47] were omitted from our model for simplicity, but could be added as new multiscale mechanobiological questions are posed regarding their mechanics. Lastly, our multiscale framework could be broadened to reveal the nano-and micro-mechanics within nascent engineered tissues and organ-chips that apply controllable biophysical loads at the cell membrane [48][49][50][51][52][53] .…”

“…Lastly, our multiscale framework could be broadened to reveal the nano-and micro-mechanics within nascent engineered tissues and organ-chips that apply controllable biophysical loads at the cell membrane [48][49][50][51][52][53] .…”