Decellularized Adipose Matrices Can Alleviate Radiation-Induced Skin Fibrosis

Adem, Sandeep; Abbas, Darren; Lavin, Christopher V.; Fahy, Evan J.; Deleon, Nestor M. Diaz; Borrelli, Mimi R.; Mascharak, Shamik; Shen, Abra H.; Patel, Ronak A.; Longaker, Michael T.; Nazerali, Rahim; Wan, Derrick C.

doi:10.1089/wound.2021.0008

Cited by 18 publications

(20 citation statements)

References 46 publications

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“…Following this, a computational algorithm was used to analyze the collagen structure of the skin to determine the extracellular matrix (ECM) pattern in both wound and unwounded human and murine skin. 2,10,11…”

Section: Methodsmentioning

confidence: 99%

“…he field of wound healing, developmental biology, and tissue regeneration is often at the forefront of scientific discovery, with its combination of foundational scientific principles and clinical prevalence coupled with expanding use and growth of biotechnological advances. [1][2][3] However, the translation of these scientific discoveries into clinical applications is a continual work in progress, as the genetic heterogeneity between small animals, such as mice or rodents, and humans is complex. 4 Simulating viable, human tissue in a laboratory, preclinical setting is extremely beneficial to bridging this gap.…”

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confidence: 99%

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Establishing a xenograft model with CD-1 nude mice to study human skin wound repair

Abbas

Fahy²,

Spielman³

et al. 2023

Plastic &Amp; Reconstructive Surgery

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Background: A significant gap exists in the translatability of small-animal models to human subjects. One important factor is poor laboratory models involving human tissue. Thus, the authors have created a viable postnatal human skin xenograft model using athymic mice. Methods: Discarded human foreskins were collected following circumcision. All subcutaneous tissue was removed from these samples sterilely. Host CD-1 nude mice were then anesthetized, and dorsal skin was sterilized. A 1.2-cm-diameter, full-thickness section of dorsal skin was excised. The foreskin sample was then placed into the full-thickness defect in the host mice and sutured into place. Xenografts underwent dermal wounding using a 4-mm punch biopsy after engraftment. Xenografts were monitored for 14 days after wounding and then harvested. Results: At 14 days postoperatively, all mice survived the procedure. Grossly, the xenograft wounds showed formation of a human scar at postoperative day 14. Hematoxylin and eosin and Masson trichome staining confirmed scar formation in the wounded human skin. Using a novel artificial intelligence algorithm using picrosirius red staining, scar formation was confirmed in human wounded skin compared with the unwounded skin. Histologically, CD31+ immunostaining confirmed vascularization of the xenograft. The xenograft exclusively showed human collagen type I, CD26+, and human nuclear antigen in the human scar without any staining of these human markers in the murine skin. Conclusion: The proposed model demonstrates wound healing to be a local response from tissue resident human fibroblasts and allows for reproducible evaluation of human skin wound repair in a preclinical model. Clinical Relevance Statement: Radiation-induced fibrosis is a widely prevalent clinical phenomenon without a well-defined treatment at this time. This study will help establish a small-animal model to better understand and develop novel therapeutics to treat irradiated human skin.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Establishing a xenograft model with CD-1 nude mice to study human skin wound repair

Abbas

Fahy²,

Spielman³

et al. 2023

Plastic &Amp; Reconstructive Surgery

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“…of 30 Greys (Gy) external beam radiation to the dorsum, delivered as six fractionated doses of 5 Gy every other day over the course of 12 days total (Kimtron Polaris SC-500; Kimtron Inc., Oxford, CT), followed by 4 weeks of recovery to allow for the development of fibrosis. 4,23,24 Lead shielding was used to isolate exposure to only the dorsa. All experiments were performed under an approved APLAC protocol (APLAC #31212) in accordance with the Stanford University Animal Care and Use Committee Guidelines.…”

Section: Irradiated Animals Without Excisional Woundingmentioning

confidence: 99%

“…Polarized images of Picrosirius Red-stained slides were colour deconvoluted, binarized, and skeletonized using a MATLAB algorithm as previously described. 4,13,23,26 294 parameters of red and green polarized collagen fibres were extracted (including brightness, number, length, width, persistence, angle, branch points, Euler number, extent, perimeter, solidity, eccentricity, equivalent diameter, etc. ), measured, and reduced by Uniform Manifold Approximation and Projection (UMAP) to generate two-dimensional plots to visualize collective differences in the collagen fibre network patterns between groups.…”

Section: Machine-learning Algorithm Analysis Of Extracellular Matrix ...mentioning

confidence: 99%

Deferoxamine topical cream superior to patch in rescuing radiation‐induced fibrosis of unwounded and wounded skin

Berry,

Abbas,

Griffin

et al. 2024

J Cellular Molecular Medi

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Topical patch delivery of deferoxamine (DFO) has been studied as a treatment for this fibrotic transformation in irradiated tissue. Efficacy of a novel cream formulation of DFO was studied as a RIF therapeutic in unwounded and excisionally wounded irradiated skin. C57BL/6J mice underwent 30 Gy of radiation to the dorsum followed by 4 weeks of recovery. In a first experiment, mice were separated into six conditions: DFO 50 mg cream (D50), DFO 100 mg cream (D100), soluble DFO injections (DI), DFO 1 mg patch (DP), control cream (Vehicle), and irradiated untreated skin (IR). In a second experiment, excisional wounds were created on the irradiated dorsum of mice and then divided into four treatment groups: DFO 100 mg Cream (W‐D100), DFO 1 mg patch (W‐DP), control cream (W‐Vehicle), and irradiated untreated wounds (W‐IR). Laser Doppler perfusion scans, biomechanical testing, and histological analysis were performed. In irradiated skin, D100 improved perfusion compared to D50 or DP. Both D100 and DP enhanced dermal characteristics, including thickness, collagen density and 8‐isoprostane staining compared to untreated irradiated skin. D100 outperformed DP in CD31 staining, indicating higher vascular density. Extracellular matrix features of D100 and DP resembled normal skin more closely than DI or control. In radiated excisional wounds, D100 facilitated faster wound healing and increased perfusion compared to DP. The 100 mg DFO cream formulation rescued RIF of unwounded irradiated skin and improved excisional wound healing in murine skin relative to patch delivery of DFO.

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“…Acute injuries induced by ray is characterized by skin erythema, desquamation, ulceration, hemorrhage, and necrosis. Chronic injuries induced by ray shows skin atrophy, alopecia and vascular dilation ( 3 , 4 ). Different from the conventional skin and soft tissue injury, the irradiated skin and soft tissue injury can lead to delayed cancer treatment, reduced patient’s quality of life, and even endanger the patient’s life in severe cases.…”

Section: Introductionmentioning

confidence: 99%

Promoting repair of highly purified stromal vascular fraction gel combined with advanced platelet-rich fibrin extract for irradiated skin and soft tissue injury

Li¹,

Gan²,

Liang³

et al. 2022

Ann Transl Med

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Background To evaluate the effect of highly purified stromal vascular fraction gel (SVFG) combined with advanced platelet-rich fibrin extract (APRFE) in treatment of irradiated skin and soft tissue injury. Methods The subcutaneous fat and whole blood of 4 rabbits were collected to isolate the SVFG and APRFE, respectively. Forty-eight rabbits were divided into 4 groups to prepare irradiated skin injury models with 25 Gy for 24 hours; corresponding dose were performed subcutaneously injected into wounds. In group A, the rabbits were treated with 0.3 mL APRFE combined with 1 mL SVFG. In group B, the rabbits were treated with 1 mL SVFG. In group C, the rabbits were treated with 0.3 mL APRFE, and group D was treated with 1 mL normal saline. The wound healing was detected on the 2, 5, 9 and 14 d after intervention. The wounds tissue was cut for hematoxylin and eosin (HE) staining to observe the structure and Masson staining to observe the collagen content. The expression of CD31 in each group was detected by immunohistochemistry (IHC), the protein and mRNA levels of K19, hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), interleukin 8 (IL-8) and interleukin 10 (IL-10) were detected respectively by Western blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) on 7, 14 and 28 d after intervention. Results It is revealed that wound healing rates from 5 to 14 d in group A was significantly higher than that of control. The wounds healing rates in group B and C were significantly higher than that of control after 12 d. Masson staining results showed that the collagen content in group A was significantly higher than that of the other 3 groups on the 7, 14 and 28 d. The results of IHC showed that the expression of CD31 in group A was significantly higher than that of the other 3 groups on 7, 14 and 28 d. WB and RT-PCR results showed that relative expression levels of K19, HIF-1α, VEGF, IL-10 in group A were significantly higher than that of the other 3 groups on 7, 14 and 28 d. However, the relative expression levels of IL-8 in group A was significantly lower than that of the other 3 groups on 7, 14 and 28 d. Conclusions SVFG combined with APRFE can promote the repair of irradiated skin and soft tissue injury by accelerating angiogenesis, promoting collagen synthesis and reducing inflammation.

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Decellularized Adipose Matrices Can Alleviate Radiation-Induced Skin Fibrosis

Cited by 18 publications

References 46 publications

Establishing a xenograft model with CD-1 nude mice to study human skin wound repair

Establishing a xenograft model with CD-1 nude mice to study human skin wound repair

Deferoxamine topical cream superior to patch in rescuing radiation‐induced fibrosis of unwounded and wounded skin

Promoting repair of highly purified stromal vascular fraction gel combined with advanced platelet-rich fibrin extract for irradiated skin and soft tissue injury

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