# Local ADSC Delivery Methods Accelerate Healing of Large Unburned Full-Thickness Skin Defects by Promoting an Optimal Wound Microenvironment

**Authors:** Semra Gürünlüoğlu, Basri Satılmış, Mehmet Gül, Muhammed Dündar, Kubilay Gürünlüoğlu, Ezgi Karaaslan, Ahmet Koç, Mehmet Aslan, Sezai Yılmaz, Mehmet Demircan, Tevfik Tolga Şahin

PMC · DOI: 10.3390/biom16020320 · Biomolecules · 2026-02-18

## TL;DR

This study shows that delivering adipose-derived stem cells improves healing of large skin defects by creating a better wound environment.

## Contribution

The study introduces a new large skin defect model and compares two ADSC delivery methods for wound healing.

## Key findings

- ADSC-treated groups showed faster wound healing and better microenvironment conditions from day 14.
- Complete wound closure occurred by day 32 in the ADSC injection group, unlike other groups.
- Local ADSC application modulates the wound microenvironment to accelerate healing.

## Abstract

Background: This study introduces an experimental model of a large, full-thickness skin defect and evaluates how adipose-derived stem cells characterized by high self-renewal and differentiation capacity affect both wound healing and the wound microenvironment when delivered using two different local application methods. Materials and Methods: In this preclinical study, we established an excisional full-thickness skin defect model involving approximately 30% of the total body surface area (TBSA). Five experimental groups were formed, each containing equal numbers of male and female rats: (1) subdermal ADSC injection (ADSC-I) (n = 8), (2) application of an acellular dermal matrix (ADM) seeded with ADSCs (n = 8) (ADSC-ADM), (3) ADM alone (n = 8), (4) subdermal saline injection (n = 8) (SS-I), and (5) an untreated skin-defect sham group (n = 8). Wound healing and wound microenvironment parameters were assessed at regular intervals using macroscopic and microscopic evaluations, as well as various quantitative measurements. The study was terminated when complete wound closure was achieved in all animals of at least one experimental group. Results: The most favorable healing outcomes were observed in the two ADSC-treated groups. More favorable microenvironmental conditions in the stem cell groups were detected from day 14 onward. Complete closure of the dermal defects occurred by day 32 in the ADSC-I group, whereas none of the other groups achieved full wound closure within the study period. Conclusions: Local application of adipose-derived stem cells may accelerate wound healing by favorably modulating the wound microenvironment.

## Linked entities

- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Tert (telomerase reverse transcriptase) [NCBI Gene 301965], Cd44 (CD44 molecule) [NCBI Gene 25406] {aka CD44A, METAA, RHAMM}, Adm (adrenomedullin) [NCBI Gene 25026] {aka Ap, H39316, RATAP}, Rps6 (ribosomal protein S6) [NCBI Gene 29304], ADM (adrenomedullin) [NCBI Gene 133] {aka AM, PAMP}, Thy1 (Thy-1 cell surface antigen) [NCBI Gene 24832] {aka CD7}
- **Diseases:** erythema (MESH:D004890), Necrotic (MESH:D009336), Skin Defect (MESH:D012868), diabetic wounds (MESH:D003920), edema (MESH:D004487), fibrosis (MESH:D005355), injury to (MESH:D014947), inflammation (MESH:D007249), skin (MESH:D012871), skin injuries (MESH:D000069836), Burn injuries (MESH:D002056), ADSC (MESH:D000092423), itching (MESH:D011537), rash (MESH:D005076)
- **Chemicals:** amphotericin B (MESH:D000666), H&amp;E (MESH:D006371), DMEM (-), puromycin (MESH:D011691), penicillin (MESH:D010406), Hematoxylin (MESH:D006416), eosin (MESH:D004801), 3,3'-Diaminobenzidine (MESH:D015100), formalin (MESH:D005557), glucose (MESH:D005947), CO2 (MESH:D002245), Vaseline (MESH:D010577), polybrene (MESH:D006583), xylazine (MESH:D014991), EDTA (MESH:D004492), FITC (MESH:D016650), lactate (MESH:D019344), xylene (MESH:D014992), streptomycin (MESH:D013307), Trypan Blue (MESH:D014343), methanol (MESH:D000432), Saline (MESH:D012965), Paraffin (MESH:D010232), paracetamol (MESH:D000082), oxygen (MESH:D010100), PS (MESH:D010758), ethanol (MESH:D000431), FuGENE (MESH:C411955)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Felis catus (cat, species) [taxon 9685], Homo sapiens (human, species) [taxon 9606], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Canis lupus familiaris (dog, subspecies) [taxon 9615]
- **Cell lines:** SVF — Homo sapiens (Human), Telomerase immortalized cell line (CVCL_UI86), HEK 293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), ADSC — Homo sapiens (Human), Somatic stem cell (CVCL_WG55)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937722/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937722/full.md

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Source: https://tomesphere.com/paper/PMC12937722