Rapid Fabrication of Living Tissue Models by Collagen Plastic Compression: Understanding Three-Dimensional Cell Matrix Repair In Vitro

Abstract

Objective: To produce biomimetic collagen scaffolds for tissue modeling and as tissue-engineered implants. Approach: Control of collagen fibril material parameters in collagen hydrogel scaffolds by using plastic compression (PC), resulting in direct control of cell proliferation, cell migration, and cell-cell interaction. Results: We were able to control the density of collagen in such scaffolds from between 0.2% and 30%, and controllably layer the fibrils in the Z-plane. Cell migration was observed in gels where a gradient of collagen density was present. In these gels, cells preferentially migrated toward the collagen-dense areas. Cell proliferation rates were measurably higher in dense collagen gels. Innovation: The use of PC to control material properties of collagen hydrogels results in collagen scaffolds that are biomimetic. These collagen gels reproduce the relevant matrix-mechanical environment in which behavior is more representative of that found in vivo. Conclusion: The material properties of native collagen type I gels can be engineered to match those found in tissues in vivo to elicit more biomimetic cell behavior.

Mechanisms and Microenvironment Investigation of Cellularized High Density Gradient Collagen Matrices via Densification

“…Additionally, this work adds to the current literature of compressed collagen matrices, examining the unique gradient features induced by the compression modality. This work shows similar effects of collagen matrix compression utilizing controlled strain rates [5] . Induced gradient matrices are mechanically robust and their ability to encapsulate cells allows for unique investigation of cellular response to specific and controlled microenvironments of various properties.…”

“…Collagen is the primary structural material of connective tissues, giving rise to much of the structural integrity of the tissue, and is a primary matrix component with which cells physically and chemically interact. Moreover, recent research has shown that collagen matrices can be formed into 3D matrices with near tissue-like properties [5, 6] . Integrin binding sequences in the collagen structure act as signaling mechanisms, driving gene and protein expression similar to native physiology [7] .…”

An in vitro investigation into the effects of 10 Hz cyclic loading on tenocyte metabolism

“…The tenocyte suspension and neutralized collagen solution were mixed 1:9 (0.4 mg/mL collagen, 0.1 × 10 6 cells/mL final density), and 5 mL was pipetted into a rectangular mold and allowed to incubate at room temperature for 30 minutes to solidify. The resulting highly hydrated gels were placed between pieces of absorbent filter paper, and a 120 g weight placed on top for 5 minutes to exude water and leave the gels as a 100‐ to 200‐μm‐thick collagen sheet in a process coined “plastic compression” …”

Electroactive biomimetic collagen-silver nanowire composite scaffolds

“…Plastic compression of collagen, a technique for making collagen meshes, utilizes fibril reassembly to make tissue-like constructs mimicking the in vivo extracellular matrix (ECM). 18,19 Collagen on its own in not conductive, and has consequently limited capabilities in electrical stimulation of cells. The introduction of conductive components to a collagen system would hence allow for a biomimetic material that could improve stimulation, regeneration and remodeling of tissues relying on electrical stimulation.…”