Micropatterning Decellularized ECM as a Bioactive Surface to Guide Cell Alignment, Proliferation, and Migration

Abstract

Bioactive surfaces and materials have displayed great potential in a variety of tissue engineering applications but often struggle to completely emulate complex bodily systems. The extracellular matrix (ECM) is a crucial, bioactive component in all tissues and has recently been identified as a potential solution to be utilized in combination with biomaterials. In tissue engineering, the ECM can be utilized in a variety of applications by employing the biochemical and biomechanical cues that are crucial to regenerative processes. However, viable solutions for maintaining the dimensionality, spatial orientation, and protein composition of a naturally cell-secreted ECM remain challenging in tissue engineering. Therefore, this work used soft lithography to create micropatterned polydimethylsiloxane (PDMS) substrates of a three-dimensional nature to control cell adhesion and alignment. Cells aligned on the micropatterned PDMS, secreted and assembled an ECM, and were decellularized to produce an aligned matrix biomaterial. The cells seeded onto the decellularized, patterned ECM showed a high degree of alignment and migration along the patterns compared to controls. This work begins to lay the groundwork for elucidating the immense potential of a natural, cell-secreted ECM for directing cell function and offers further guidance for the incorporation of natural, bioactive components for emerging tissue engineering technologies.

Robust Topographical Micro-Patterning of Nanofibrillar Collagen Gel by In Situ Photochemical Crosslinking-Assisted Collagen Embossing

“…The investigation of the in vitro NIH 3T3 cell culture described in the paper confirmed the practical applicability of the proposed IPC-CE construct for biomedical applications, as well as its structural robustness and the topographical effect of the micro-ridge patterns. Many previous studies have shown that the NIH 3T3 cells tend to be elongated and oriented along anisotropic topographies, as a result of contact guidance by nanoscale patterns or geometrical confinement by microscale patterns (>10 μm) [ 6 , 33 , 34 , 35 ]. Our results showed that the micro-ridge patterns on the IPC-CE construct favorably promoted both the elongation and orientation of cells along the micro-ridges by geometrical confinement, which stably maintained their structure during the cell culture period, whereas the conventional constructs lost their topographical effect following rehydration.…”

Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases

“…To control cell shape and area by micropatterning, PDMS stamps with square/rectangular or line patterns were prepared by standard photolithography using photoresist SU-8 2010 (Microchem Corp, Newton, MA, USA), which is detailed elsewhere [ 14 , 91 ]. The patterned side of the PDMS stamp was incubated with 50 µg/mL laminin solution for 1 h before bringing it into conformal contact with the cell culture substrate for 5 min.…”

A Unification of Nanotopography and Extracellular Matrix in Electrospun Scaffolds for Bioengineered Hepatic Models

“…Another feature of these platforms is their composition; in healthy tissue, ECM plays a vital role in supporting cell growth and behavior by providing structural, mechanical, and bioactive cues . In recent years, single and multiple ECM proteins have been incorporated into polymer scaffolds to improve their biocompatibility and function. − However, a single protein cannot mimic all functions attributed to whole ECM. , Whole-organ decellularized ECM incorporated into artificial scaffolds has shown advantages such as affecting hydrophilicity, cell adhesion, proliferation, and behavior. ,− This has also been seen with hepatocytes, with studies showing that rat and human liver dECM can impact cell survival and proliferation. ,,, …”

“…To date, the focus on scaffold topography and dECM combinations has mainly been investigated on the macroscale. ,− However, limited attention has been devoted to the synergistic effects of topographical and biochemical cues on hepatocytes for liver tissue engineering. We have therefore developed a new protocol to incorporate the perfusion of whole-organ decellularized rat liver ECM into electrospun fibers with surface depressions to explore the combined effect on human hepatic carcinoma cells (HepG2).…”