Tissue assembly guided via substrate biophysics: applications to hepatocellular engineering

Area of Science:

• Biomaterials Science
• Cell Biology
• Tissue Engineering

Background:

• The cellular microenvironment's biophysical and biochemical properties significantly influence multicellular development (morphogenesis) and cell function.
• Hepatocellular (liver cell) morphology is closely linked to its functional output, making it crucial for designing supportive materials.

Purpose of the Study:

• To review how biophysical factors regulate hepatocellular morphogenesis and function.
• To explore how biochemical cues enhance cellular responsiveness to biophysical stimuli.
• To highlight strategies for controlling liver cell assembly and function in tissue engineering.

Main Methods:

• Examined substrate microtopography (e.g., pore size in collagen sponges and PGLA foams) to observe its effect on cellular organization.
• Investigated substrate mechanical compliance (e.g., crosslinking of Matrigel and polyacrylamide gels) to assess its impact on cellular reorganization.
• Analyzed the interplay between biophysical parameters and biochemical cues (e.g., extracellular matrix ligands, growth factors).

Main Results:

• Substrate microtopography influenced whether cells formed 2-D structures or 3-D assemblies, correlating with cell function.
• Substrate mechanical compliance directed cells towards 2-D (rigid) or 3-D (malleable) reorganization.
• Both biophysical and biochemical factors, including extracellular matrix and growth factors, were critical in governing morphogenesis and cell function.

Conclusions:

• Substrate biophysics, including microtopography and mechanical properties, can effectively control hepatocellular morphogenesis.
• Biochemical cues can significantly enhance the effects of biophysical stimuli on liver cell development and function.
• Rational manipulation of these factors offers novel strategies for hepatic tissue engineering and controlling liver-specific functions.