# Integration of Fibroblast-Populated Collagen Lattices and Perfusable Micro-Physiological Systems: A Mechanobiologically Unified Framework for Living Devices

**Authors:** Kawmini Appuhami, Aya Nakamura-Norimoto, Yasuyuki S. Kida

PMC · DOI: 10.3390/mi17020171 · Micromachines · 2026-01-28

## TL;DR

This paper proposes a new framework that unifies fibroblast tension and vascular flow to better model tissue mechanics in living devices.

## Contribution

The paper introduces a mechanobiological framework that unifies stromal tension and vascular shear as a novel axis for tissue modeling.

## Key findings

- FPCLs generate tension and remodel matrices relevant to disease modeling.
- MPSs emphasize vascular dynamics and shear stress in tissue function.
- A crosstalk paradigm unifies stromal and vascular forces in tissue physiology.

## Abstract

This review proposes mechanical crosstalk between stromal tension and vascular shear/flow as a unifying principle for integrating fibroblast-populated collagen lattices (FPCLs) with perfusable micro-physiological systems (MPSs). We argue that current in vitro platforms either emphasize fibroblast-driven matrix contraction (as with FPCLs) or flow-mediated vascular dynamics (as with MPSs) but rarely consider the reciprocity between these forces. By defining a mechanobiological framework that couples cellular contractility, extracellular matrix (ECM) remodeling, and shear-dependent endothelial responses, we reframe FPCL–MPS hybrids as “living devices” capable of capturing mechano-transduction across stromal and vascular compartments. This review (1) delineates the mechanobiology of FPCLs, highlighting their tension generation, matrix remodeling, and disease relevance; (2) surveys perfusable MPS design principles, focusing on shear stress, barrier function, and multicellular integration; (3) formulates a crosstalk paradigm in which stromal tension and vascular shear coregulate tissue physiology; (4) synthesizes engineering strategies for integrating FPCLs into MPSs; and (5) outlines challenges and future directions involving multiscale measurements, multi-omics, artificial intelligence, and regulatory standardization. To our knowledge, this review is among the first to explicitly frame stromal tension and vascular shear as a unified mechanobiological axis.

## Full-text entities

- **Genes:** ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, NOS3 (nitric oxide synthase 3) [NCBI Gene 4846] {aka EC-NOS, ECNOS, MYMY8, NOSIII, cNOS, eNOS}, MYH14 (myosin heavy chain 14) [NCBI Gene 79784] {aka DFNA4, DFNA4A, FP17425, MHC16, MYH17, NMHC II-C}, KLF2 (KLF transcription factor 2) [NCBI Gene 10365] {aka LKLF}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, PIEZO1 (piezo type mechanosensitive ion channel component 1 (Er blood group)) [NCBI Gene 9780] {aka DHS, ER, FAM38A, LMPH3, LMPHM6, Mib}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, MAPK7 (mitogen-activated protein kinase 7) [NCBI Gene 5598] {aka BMK1, ERK4, ERK5, PRKM7}
- **Diseases:** toxicity (MESH:D064420), metastasis (MESH:D009362), FPCL (MESH:D003095), cancer (MESH:D009369), pancreatic cancer (MESH:D010190), PDAC (MESH:C537768), injury to (MESH:D014947), Pancreatic Ductal Adenocarcinoma (MESH:D021441), cardiac fibrosis (MESH:D005355), fibrotic disorders (MESH:D009358), burn (MESH:D002056), MPS (MESH:C536681), hypoxic (MESH:D002534)
- **Chemicals:** etoposide (MESH:D005047), silicon-nitride (MESH:C032734), BioRender (-), DMSO (MESH:D004121), glucose (MESH:D005947), polymers (MESH:D011108), poly (ethylene glycol) (MESH:D011092), oxygen (MESH:D010100), daunorubicin (MESH:D003630)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** Capan-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0237)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943255/full.md

## References

68 references — full list in the complete paper: https://tomesphere.com/paper/PMC12943255/full.md

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Source: https://tomesphere.com/paper/PMC12943255