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Revealing Early Spatial Patterns of Cellular Responsivity in Fiber-Reinforced Microenvironments
Saitheja A Pucha1,2, Maddie Hasson1,2, Hanna Solomon1,2
1Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.
Tissue Engineering. Part A
|March 22, 2024
Summary
Engineered tissue scaffolds using fiber reinforcement show early cell patterning influenced by fiber orientation and material properties. Understanding these microscale cell-fiber interactions guides macroscale tissue regeneration strategies.
Area of Science:
- Biomaterials Engineering
- Tissue Engineering
- Cellular Mechanics
Background:
- Fiber-reinforced scaffolds are crucial for replacing damaged tissues, aiming to mimic native anisotropic properties.
- Current research often overlooks microscale cell-biomaterial interactions, which are vital for tissue remodeling and organization.
- Early cellular responses to fiber-reinforced microenvironments significantly impact the success of regenerative therapies.
Purpose of the Study:
- To investigate the influence of spatial orientation, substrate stiffness, and matrix remodeling on early cell-fiber interactions in engineered constructs.
- To elucidate how these microenvironmental factors guide cellular behavior and extracellular matrix organization.
- To identify trends in cellular patterning within fiber-reinforced biomaterials for optimized tissue engineering.
Main Methods:
- Cultured bovine mesenchymal stromal cells (MSCs) in fibrin gels reinforced with polyglycolide-co-caprolactone fibers.
- Modulated gel stiffness and remodeling capacity via fibrinogen concentration and aprotinin treatment.
- Utilized machine learning (PCA and hierarchical clustering) to analyze cell morphology, YAP localization, and spatial features relative to fibers.
Main Results:
- Cellular morphology and YAP localization showed weak correlations with distance from fibers, indicating heterogeneity.
- Machine learning identified three distinct cell clusters (high, medium, low response) based on morpho-mechanoresponse.
- High-response cells were predominantly near fibers, while low-response cells were further away, with stiffness and remodeling capacity differentially affecting their distribution and response.
Conclusions:
- Early cell-fiber interactions in reinforced biomaterials are complex and heterogeneous.
- Spatial orientation, substrate stiffness, and remodeling capacity significantly influence cellular mechanoresponses and patterning.
- These findings provide a foundation for designing microscale scaffold architectures to enhance macroscale tissue assembly and regeneration.
