Arnaldo Rizzo, MD – Morphodynamic Cosmetic Surgery
Abstract
Recent discoveries in mechanobiology, particularly the work of Li et al. (2025), have revealed that direct cell-to-cell contact can induce fibroblast-to-myofibroblast transition independently of traditional biochemical or extracellular mechanical cues. This finding redefines fibrosis as a mechanical and communicative dysfunction, rather than merely an inflammatory or biochemical event. Understanding this mechanism provides new therapeutic strategies for preventing or reversing fibrotic tissue transformation through controlled mechanical modulation and morphodynamic rebalancing.
1. The New Mechanobiological Paradigm of Fibrosis
Fibrosis has long been attributed to TGF-β–driven biochemical cascades and extracellular matrix (ECM) stiffening. However, Li et al. demonstrated that fibroblasts can be activated by direct physical contact with neighboring cells.
This contact-dependent mechanosignaling activates β-catenin, YAP/TAZ, and cytoskeletal reorganization, leading to the expression of α-SMA and the acquisition of a contractile myofibroblast phenotype.
The process unfolds even in the absence of external strain or cytokines, showing that intercellular junctions themselves act as mechanosensors capable of translating proximity and compression into transcriptional responses.
2. Clinical Implications: From Static Compression to Dynamic Regulation
In tissue repair or after surgery, fibroblasts often accumulate and form dense cellular aggregates within confined mechanical environments. Excessive crowding increases junctional signaling, promoting persistent activation and ECM contraction.
Thus, fibrosis may arise not from inflammation alone but from local mechanical immobility—a loss of morphodynamic flexibility.
Restoring mobility through controlled mechanical stimuli can interrupt this self-perpetuating loop, promoting regenerative reorganization.
3. Mechanobiological Therapeutic Strategies
3.1 Soft Mechanical Stimulation (Hormetic Principle)
Gentle, periodic mechanical input—through fascial micromobilization, manual therapy, or morphodynamic massage—applies low-grade, adaptive stress that reactivates normal mechanotransduction without provoking inflammation (Rizzo 2023).
These hormetic stimuli reduce intercellular compression, down-regulate YAP/TAZ and α-SMA, and favor fibroblast reversion to a quiescent regenerative phenotype (Calabrese & Baldwin 2003; Mattson 2008).
3.2 Functional Micromovement and Controlled Stretching
Mild cyclic stretching reorganizes collagen fibers and stimulates nitric oxide release, which inhibits TGF-β1 and prevents pathological contracture (Ogawa 2011).
This reintroduces functional dynamism to the tissue—echoing the morphodynamic principle that form adapts to functional motion.
3.3 Low-Energy Physical Therapies
Subthermal radiofrequency, low-frequency vibration, and microcurrent biostimulation produce micro-oscillatory forces that disrupt excessive adhesion and re-establish viscoelastic balance without mechanical trauma (Martino et al. 2018).
3.4 Regenerative Biologic Synergy
PRP, PRF, or mechanically preconditioned exosomes modulate local cytokine balance and inhibit the fibroblast-to-myofibroblast transition (Kim et al. 2021; Trubiani et al. 2019).
When combined with morphodynamic mechanical cues, they enhance controlled collagen remodeling and functional tissue regeneration.
4. Mechanobiological Synthesis
| Mechanical Context | Cell Density / Contact | Mechanosignaling | Biological Outcome |
|---|---|---|---|
| Immobility / Chronic Compression | ↑ Cell proximity | ↑ β-catenin, YAP/TAZ | Fibrosis, stiffening |
| Gentle Dynamic Stimulation | ↓ Effective contact | ↓ α-SMA, ↓ TGF-β | Regeneration, flexibility |
| Excessive Force / Trauma | ↑ Damage, inflammation | ↑ ROS, cytokine surge | Pathologic scarring |
5. Toward Functional Morphodynamics
Therapeutically, reducing cellular density does not mean destroying cells but restoring space and motion at the microscale.
This can be achieved by soft mechanical decompression, fluidic mobility, and dynamic remodeling of the ECM.
Within the conceptual framework of Morphodynamic Cosmetic Surgery, fibrosis is thus interpreted as a loss of mechanical dialogue—a frozen pattern of tension that can be re-educated by controlled motion.
In this sense, mechanotherapy becomes morphotherapy:
Soft motion regenerates, stiffness scars.
Key References
- Li C., Wang Y., Zhang Y., et al. (2025). Physical contact drives fibroblast-to-myofibroblast transition independent of biochemical or mechanical cues. bioRxiv.
- Rizzo A. (2023) Chirurgia Cosmetica Morfodinamica. Available on line: https://www.chirurgiacosmeticamorfodinamica.it/2024/03/27/fibrosi/
- Ogawa R. (2011). Mechanobiology of scarring. Wound Repair Regen., 19(Suppl 1): S2–S9.
- Martino F., et al. (2018). Cellular mechanotransduction: From tension to function. Front Physiol., 9:824.
- Trubiani O., Marconi G.D., et al. (2019). Mechanobiology of human periodontal ligament stem cells: insights into exosome biogenesis and function. Front Physiol., 10:1509.
- Kim J., Kim H., Jeon J., et al. (2021). Exosomes and regenerative medicine: Mechanobiological implications in wound healing. Stem Cells Int., 2021:6697576.
- Calabrese E.J., Baldwin L.A. (2003). Hormesis: The dose–response revolution. Annu Rev Pharmacol Toxicol., 43:175–197.
- Mattson M.P. (2008). Hormesis defined. Aging Res Rev., 7(1):1–7.
