Decoding Cell–Microenvironment Crosstalk in Development, Regeneration, and Disease: Elucidating the molecular, biochemical and biomechanical pathways that drive tissue fate across life and pathology

Tissue development, regeneration, and disease progression are orchestrated through intricate crosstalk between cells and their surrounding microenvironment. This dynamic interplay involves molecular signaling, mechanical forces, and structural remodeling that collectively guide morphogenesis, lineage specification, and repair. From embryogenesis to organogenesis, and from tissue engineering to pathological remodeling, understanding how cells interpret and respond to their niche remains a central challenge in developmental and regenerative biology.

The microenvironment—comprising extracellular matrix (ECM), soluble factors, biomechanical cues, and metabolic modulators—acts as both a scaffold and a signaling hub. Its composition and mechanics influence stem cell fate, epigenetic remodeling, and tissue patterning, while its dysregulation contributes to disease progression and impaired repair. Recent advances in organoid systems, bioengineered scaffolds, and spatial omics technologies now allow high-resolution mapping of these cell–niche interactions. However, translating these insights into therapeutic strategies remains a key frontier for the field.



The overarching goal of this Research Topic is to elucidate how developmental principles, cellular interfaces, and mechanobiological cues converge to regulate tissue regeneration, signaling pathways, cell fate decisions, and pathological processes. By integrating insights from molecular signaling, extracellular matrix biology, mechanobiology, biofabrication, and computational/AI modeling, this topic seeks to inspire translational strategies in regenerative medicine, oncology, neuroscience, and tissue engineering.

We invite researchers to contribute original research articles, reviews, and perspectives in the following areas:



Cell and developmental biology

Stem cell research and regenerative medicine

Cancer biology and neurobiology

Extracellular matrix biology and biomaterials science

Vascular, cartilage, and bone tissue engineering



This Research Topic aims to define and decode cell–microenvironment interactions across developmental, regenerative, and disease contexts. We invite original research articles, reviews, and perspectives that integrate cellular and developmental biology with regenerative medicine, biomaterials science, and disease modeling. Studies using vertebrates, invertebrates, organoids, and synthetic constructs are encouraged to ensure conceptual breadth and translational relevance.



Specifically, we welcome manuscripts that address:



- Mechanisms underlying stem cell–ECM interactions that regulate cell fate decisions, morphogenesis, and regenerative potential.

- Interplay between developmental signaling and epigenetic regulation including how morphogen gradients, transcriptional networks, and histone mutation–driven chromatin dynamics shape morphogenesis and lineage specification.

- Dynamics of ECM remodeling across physiological and pathological contexts, with a focus on matrix turnover in development, cancer, and neurodegeneration.

- Roles of microenvironmental and epigenetic modulators- such as reactive oxygen species (ROS), oxidative stress, apoptosis, and histone mutation–associated chromatin remodeling—in directing cell fate during tissue adaptation, regeneration, and disease progression.

- Biomaterial-based strategies for microenvironment engineering including polymer scaffolds and bioinspired constructs that emulate developmental niches or direct regeneration.

- Mechanobiology-driven frameworks that elucidate tissue formation and guide engineered regenerative processes in vitro.

- Computational and AI-enabled approaches that model or predict tissue formation and regeneration by integrating mechanobiological and molecular inputs, enabling in silico simulation of cell–matrix interactions, morphogenetic patterning, and dynamic ECM remodeling.



We also welcome manuscripts addressing other emerging or relevant themes within this broader scope.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Technology and Code

Keywords: Cell–microenvironment interactions, Extracellular matrix (ECM) biology, ECM dynamics, Stem cell fate, Morphogenesis, Regenerative biology, Mechanobiology, Epigenetic regulation, Chromatin remodeling, Reactive oxygen species (ROS), Oxidative stress, Apopto

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.