Myofibroblasts in Plastic Surgery

In 1971, Giulio Cesare Gabbiani first published the evidence of these cells in granulation tissue and named them ‘myofibroblast’. Fibroblasts differentiate into myofibroblast due to mechanical stress and soluble chemical factors like TGF-β1.

Myofibroblast- Definition

Myofibroblasts are specialized fibroblasts that have contractile properties like smooth muscles, remodel extra-cellular matrix (ECM), and mainly take part in wound & scar contraction, and fibrosis.

Explained in the video tutorial above are ➜ the origin, ultrastructure, evolution, mechanism of myofibroblast contraction and ECM remodelling, and its clinical relevance in relation to plastic surgery.

How are myofibroblasts different from fibroblasts?

• Shape– Myofibroblasts are stellate-shaped with long cytoplasmic extensions while fibroblasts are spindle-shaped.
• Ultrastructure (and function)– Unlike fibroblasts:

1. the cytoplasm of myofibroblasts has ‘stress fibres‘ α-smooth muscle actin (α-SMA) and cytoplasmic microfilament bundles ➜ contract like the smooth muscles;
2. the myofibroblasts have prominent rough endoplasmic retinaculum and exocytic vesicles ➜ produce a large amount of a myriad of ECM proteins: collagen types I, III, IV and VIII, glycoproteins such as fibronectin and tenascin, laminin, chondroitin sulfate, & matrix metalloproteinases (MMP)- 1, 2, and 3 ➜ ECM remodelling by Matrix straining and stiffening;
3. the myofibroblasts are strongly connected physically to their environment with transmembrane integrins called Fibronexus (FNX) adhesion complexes and cadherin-type ‘adherens junctions’ (AJ) ➜ anchor the intracytoplasmic contractile actin cytoskeleton to the surrounding ECM through ED-A (Extra Domain-A) fibronectin fibrils and to adjacent myofibroblast cells, respectively;
4. adjacent myofibroblasts have gap junctions ➜ they work as a syncytium.

Physiological effects of myofibroblast

With relevance to Plastic Surgery, here are some examples:

• All stages of Wound healing, esp. Wound contraction and remodelling, Scar contraction;
• Secondary contraction of skin grafts (Why it’s lesser for FTSG compared to SSG? ➜ see below);
• Healing after muscle, tendon, cartilage, muscle injuries, and even bony fractures- by Scar stabilization;
• Non-operative Facial Rejuvenation;
• Distraction osteogenesis.

Full-thickness skin graft- Lesser secondary contraction

Explanation: More the thickness of the dermal layer in a graft ➜ More the structurally intact dermal collagen (not dermal cells) ➜ Faster the evolution and apoptosis of myofibroblasts ➜ Lesser the secondary contraction of a graft.

Hence, full-thickness skin grafts (compared to split-skin grafts) trigger a faster decrease in the myofibroblast population, and wounds show minimal contraction. [Ref. 13,14,15]

Pathological effects of myofibroblast

Some of the conditions related to Plastic Surgery where myofibroblasts plays a role in pathogenesis are:

• Hypertrophic scar (eg. wounds healing with secondary intention, burn wounds);
• Contractures (eg. post-traumatic, post-burn, Dupuytren’s contracture);
• Joint stiffness (by peri-articular cells and synovial cell differentiation into myofibroblasts);
• Breast implant- capsular contracture;
• Neuroma formation;
• Scleroderma;
• Stromal reaction, invasion, and metastasis of various epithelial malignancies (eg. SCC).

You can help add to the above lists of ‘effects of myofibroblast’ by posting them in the comments section below.

Test Yourself!

Download slides

For further reading, please refer to:

1. Gabbiani G, Ryan GB, Majno G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia. 1971;27:549–50.
2. Ribatti D, Tamma R. Giulio Gabbiani and the discovery of myofibroblasts. Inflamm Res. 2019;68(3):241-245.
3. Tomasek, J., Gabbiani, G., Hinz, B. et al. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 3, 349–363 (2002).
4. Bochaton-piallat ML, Gabbiani G, Hinz B. The myofibroblast in wound healing and fibrosis: answered and unanswered questions. F1000Res. 2016;5.
5. Reilkoff RA, Bucala R, Herzog EL. Fibrocytes: emerging effector cells in chronic inflammation. Nat Rev Immunol. 2011;11(6):427-35.
6. Hinz B, Gabbiani G. Fibrosis: recent advances in myofibroblast biology and new therapeutic perspectives. F1000 Biol Rep. 2010;2:78.
7. Greenhalgh SN, Iredale JP, Henderson NC. Origins of fibrosis: pericytes take centre stage. F1000Prime Rep. 2013;5:37.
8. Bagalad BS, Mohan Kumar KP, Puneeth HK. Myofibroblasts: Master of disguise. J Oral Maxillofac Pathol. 2017;21(3):462-463.
9. Hinz B, Phan SH, Thannickal VJ, et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodelling. Am J Pathol. 2012;180(4):1340-55.
10. Kwan, P., Desmoulière, A., & Tredget, E. E. (2018). Molecular and Cellular Basis of Hypertrophic Scarring. Total Burn Care, 455–465.e4.
11. Klingberg F, Hinz B, White ES. The myofibroblast matrix: implications for tissue repair and fibrosis. J Pathol. 2013;229(2):298-309.
12. Montandon D, Gabbiani G, Ryan GB, Majno G: The contractile fibroblast: its relevance in plastic surgery. Plast Reconstr Surg 52:286, 1973.
13. Brown D, Garner W, Young VL: Skin grafting: dermal components in inhibition of wound contraction. South Med J 83:789, 1990.
14. Rudolph R, Suzuki M, Guber S, Woodward M: Control of contractile fibroblasts by skin grafts. Surg Forum 28:524, 1977.
15. Rudolph R: Inhibition of myofibroblasts by skin grafts. Plast Reconstr Surg 63:473, 1979. 155. 

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