# Topical Peptide Technology and the Scarring Spectrum: Linking Mechanistic Pathways to Internal Scarring (Fibrous Banding) and External Scarring (Incisional) and Outcomes in Postsurgical Healing

**Authors:** Alan D Widgerow, Laurie A Casas, Brannon Claytor, Kamakshi R Zeidler, Faiza Shafiq

PMC · DOI: 10.1093/asjof/ojaf169 · Aesthetic Surgery Journal. Open Forum · 2025-12-18

## TL;DR

This paper explores how a topical peptide formula affects both internal and external scarring after surgery, showing it improves healing outcomes.

## Contribution

The study links mechanistic pathways to both internal and external scarring, introducing a topical formulation as a new tool in surgical care.

## Key findings

- R&R significantly accelerated the resolution of internal fibrous banding compared to comparators.
- Ultrasound and histology confirmed ECM remodeling on the R&R-treated side.
- Subjective scar quality improved over time with R&R treatment.

## Abstract

Surgery results in external scars and internal scars (subcutaneous fibrous banding). Although external scarring is well understood, internal fibrous banding is less studied, despite its impact on comfort, mobility, and recovery in surgical patients. Alastin ReFORM & RePAIR COMPLEX with TriHex Technology (R&R) is a peptide-based formula that remodels the extracellular matrix (ECM). It has been tested in multiple clinical trials, showing it stimulates autophagy and macrophage repolarization. The aim was to outline the mechanistic and clinical evidence related to both internal and external scarring. They conducted a secondary analysis of 3 split-body clinical trials, with proposed mechanistic explanations extrapolated. Endpoints assessed included patient-reported outcome measures, blinded investigator ratings, ultrasound, histology, and photographic scar evaluations. Cellular secretome, interleukin-6 (IL-6) modulation, and autophagic clearance of lipid droplets and ECM remodeling provide a mechanistic explanation for the observed effects. In body contouring procedures, R&R significantly accelerated the resolution fibrous banding compared with comparators in split-body studies. Ultrasound confirmation and histology showed reconstituted ECM on the R&R-treated side. External scar assessment revealed improved subjective scar quality over time. These outcomes are mechanistically linked to the autophagic clearance of lipid droplets, ECM remodeling, and macrophage polarization, which are influenced by IL-6 and modulate the transition from inflammation to regeneration. R&R influences the spectrum of surgical scarring, affecting both internal and external scars. The scar spectrum broadens traditional views of postoperative healing, emphasizing internal fibrous banding as a measurable outcome and positioning a topical formulation as a credible additional tool in perisurgical care.

Level of Evidence: 2 (Therapeutic)

## Linked entities

- **Proteins:** IL6 (interleukin 6), MMRN1 (multimerin 1)

## Full-text entities

- **Genes:** CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, SMAD4 (SMAD family member 4) [NCBI Gene 4089] {aka DPC4, JIP, MADH4, MYHRS}, ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, SMAD7 (SMAD family member 7) [NCBI Gene 4092] {aka CRCS3, MADH7, MADH8}, TGFB3 (transforming growth factor beta 3) [NCBI Gene 7043] {aka ARVD, ARVD1, LDS5, RNHF, TGF-beta3}
- **Diseases:** limitation of movement (MESH:D045745), infection (MESH:D007239), tissue injury (MESH:D017695), discoloration (MESH:D014075), erythema (MESH:D004890), scarring (MESH:D002921), fibrosis (MESH:D005355), pigmentation (MESH:D010859), bruising (MESH:D003288), R&amp;R (MESH:C580424), Edema (MESH:D004487), trauma (MESH:D014947), scar hypertrophy (MESH:D006984), hypertrophic scarring (MESH:D017439), Pain (MESH:D010146), Ecchymosis (MESH:D004438), inflammation (MESH:D007249)
- **Chemicals:** mucopolysaccharide (MESH:D006025), Herovici (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12839518/full.md

## References

8 references — full list in the complete paper: https://tomesphere.com/paper/PMC12839518/full.md

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Source: https://tomesphere.com/paper/PMC12839518