A computational model to describe the collagen orientation in statically cultured engineered tissues
A L F Soares1, C W J Oomens, F P T Baaijens
1a Department of Biomedical Engineering , Eindhoven University of Technology , Eindhoven , The Netherlands.
Summary
Cellular contractile stresses, not just mechanical loading, are key to orienting collagen in cardiovascular tissue engineering. This finding helps understand how engineered tissues develop their essential structural integrity.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Cardiovascular Research
Background:
- Collagen provides essential mechanical strength to cardiovascular tissues, enabling them to withstand hemodynamic loads.
- Replicating a well-oriented collagen network is crucial for the functional success of tissue-engineered (TE) cardiovascular constructs.
- Current understanding primarily links collagen remodeling and orientation to mechanical loading, but orientation also occurs in static culture.
Purpose of the Study:
- To investigate the mechanism underlying collagen orientation in tissue-engineered cardiovascular constructs under static culture conditions.
- To test the hypothesis that cellular contractile stresses, rather than external mechanical loading, drive collagen orientation.
- To develop and validate a computational model integrating cellular mechanics and collagen fiber behavior.
Main Methods:
- Integrated a computational model of cellular alpha-actin turnover and stress generation.
- Coupled this cellular model with a structural constitutive model for collagen fiber mechanical behavior.
- Simulated tissue compaction, stress generation, and collagen arrangement within engineered constructs.
Main Results:
- The integrated model successfully captured the observed sample compaction in tissue-engineered constructs.
- The model demonstrated the generation of significant tissue stress originating from cellular contractile forces.
- Results indicated that cellular contractile stresses are a primary driver for the heterogeneous collagen arrangement observed.
Conclusions:
- Cellular contractile stresses, mediated by alpha-actin fibers, play a critical role in orienting collagen within tissue-engineered cardiovascular samples.
- This mechanism is significant even under static culture conditions, challenging the sole reliance on mechanical loading as the driver for collagen orientation.
- The developed model provides a valuable tool for understanding and predicting collagen organization in tissue engineering applications.
