In Vivo Stimulation of De Novo Collagen Production Caused by Cross-linked Hyaluronic Acid Dermal Filler Injections in Photodamaged Human Skin

Wang, Frank; Garza, Luis A.; Kang, Sewon; Varani, James; Orringer, Jeffrey S.; Fisher, Gary J.; Voorhees, John J.

doi:10.1001/archderm.143.2.155

Cited by 405 publications

(363 citation statements)

References 41 publications

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“…Evidence suggests that MMP-1-mediated cumulative collagen damage is a major contributor to the phenotype of aged human skin. [32][33][34][35][36] However, molecular mechanisms underlying elevated expression of MMP-1 are not well understood.…”

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confidence: 99%

Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin

Fisher

Quan

Purohit

et al. 2009

The American Journal of Pathology

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Aged human skin is fragile because of fragmentation and loss of type I collagen fibrils, which confer strength and resiliency. We report here that dermal fibroblasts express increased levels of collagen-degrading matrix metalloproteinases-1 (MMP-1) in aged (>80 years old) compared with young (21 to 30 years old) human skin in vivo. Transcription factor AP-1 and ␣2␤1 integrin, which are key regulators of MMP-1 expression, are also elevated in fibroblasts in aged human skin in vivo. MMP-1 treatment of young skin in organ culture causes fragmentation of collagen fibrils and reduces fibroblast stretch, consistent with reduced mechanical tension , as observed in aged human skin. Limited fragmentation of three-dimensional collagen lattices with exogenous MMP-1 also reduces fibroblast stretch and mechanical tension. Furthermore, fibroblasts cultured in fragmented collagen lattices express elevated levels of MMP-1, AP-1, and ␣2␤1 integrin. Importantly, culture in fragmented collagen raises intracellular oxidant levels and treatment with antioxidant MitoQ 10 significantly reduces MMP-1 expression. These data identify positive feedback regulation that couples age-dependent MMP-1-catalyzed collagen fragmentation and oxidative stress. We propose that this self perpetuating cycle promotes human skin aging. These data extend the current understanding of the oxidative theory of aging beyond a cellular-centric view to include extracellular matrix and the critical role that connective tissue microenvironment plays in the biology of aging. Skin connective tissue (dermis) provides structural support for the skin's vasculature, appendages, and epidermis, which are vital to the function of skin. Structural integrity and function of the dermis are primarily dependent on its extracellular matrix, which is primarily composed of type I collagen fibrils. Type I collagen is the most abundant structural protein in skin, 1 and fragmented collagen fibrils are prominent, characteristic features of aged human skin in vivo.2-4 This fragmentation seriously impairs both the mechanical properties of skin, and the functions of cells that reside within the dermis. Clinically, this impairment manifests as delayed wound healing, reduced vascularization, propensity to bruise, and thin skin. Failure of normal functional interactions among dermal cells and their extracellular matrix microenvironment underlie these age-dependent phenotypic alterations. 6Damage to the collagenous extracellular matrix of the dermis can be observed at both the histological and ultrastructural level. 5,[7][8][9] In young dermis, intact, tightly packed, well-organized, long collagen fibrils are abundant. In contrast, in aged dermis, collagen fibrils are fragmented, disorganized, and sparse, resulting in the appearance of amorphous open space. Quantitative biochemical analysis reveals that the amount of fragmented collagen is 4.3-fold greater in aged (Ͼ80 years old) compared with young (21 to 30 years old) human dermis in vivo.

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confidence: 99%

Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin

Fisher

Quan

Purohit

et al. 2009

The American Journal of Pathology

Self Cite

386

412

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“…It would be very arduous to recruit volunteers for a randomized placebo-controlled trial. Wang et al saline injections, was related with type I collagen deposition around the injection site [19] . Although both studies are not strictly equivalent, there is no reason to believe that LPOA skin would respond contrarily to forearm skin.…”

Section: Discussionmentioning

confidence: 99%

Lower periorbital area treatment with Restylane Vital Skinbooster

et al. 2016

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Facial aging along the periocular area has led to the development of new non-surgical therapies. The lower periorbital area (LPOA) is a vital region for facial rejuvenation and several procedures have been studied to treat it, especially procedures with dermal fillers for volume rebuilding. This manuscript aims to describe a filling technique with hyaluronic acid (HA) along the superficial layer of the lower periorbital area, presenting its effectiveness and safety. Our assessment was made by autonomous observers with pictures of before and after treatment, rated from 0 (no enhancement) to 100 (maximum enhancement). Patients' self-assessment was also performed using a visual analog scale (VAS) based on a 100-mm ruler affording a 0-100 rating. Thirty patients were enrolled in this study. The autonomous observers' evaluation presented a 78.4 mean improvement rate. Patients' self-assessments after the treatment were 0% reporting no improvement, 6.7% mild improvement, 23.3% moderate improvement, 66.7% great improvement, and 3.3% maximum improvement. Restylane Vital Skinbooster infiltration at the lower periorbital area proved to be a safe treatment. The described technique is also simple to execute, has a low rate of complications, and produces a high satisfaction rate.

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“…Moreover, Yoneda et al [20], in an animal model, highlighted that exogenous stabilized HA acts as a modulator of dermal fibroblast proliferation that modifies indirectly the synthesis of collagen. Finally, Wang et al [21] demonstrated that nonanimal stabilized HA injected into the dermal matrix is able to enhance the stimulation of de novo synthesis of type I collagen, possibly mediated by mechanical stretching and consequent activation of collagen-producing fibroblasts in the dermis.…”

Section: Discussionmentioning

confidence: 99%

Nonanimal Stabilized Hyaluronic Acid for Tissue Augmentation of the Dorsal Hands: A Prospective Study on 38 Patients

et al. 2012

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Background Often ignored, hands are one of the most telltale signs of aging. This prospective study was initiated to evaluate the effect of subcutaneous hyaluronic acid (HA) injections in aging hands, with special attention to complications and long-term outcomes. Methods Between January 2010 and December 2010, a total of 38 patients with skin phototypes II-IV and between 58 and 76 years old were treated with HA injection for aging hands. The quantity of injection never exceeded 1.0-1.5 ml HA per hand. A clinical follow-up was performed at 2 weeks, 4 weeks, 3 months, and 6 months after injection. Complications were reviewed for the whole series. At the first follow-up, 2 weeks after the procedure, ultrasound was carried out to determine if additional filling material was required. At each follow-up, patients were asked to fill out a satisfaction questionnaire. Results Nine patients developed slight ecchymosis that disappeared after 1 week. No other complications were seen in the series. Pain during the injection and discomfort after the procedure were minimal. At the 2-week follow-up, after ultrasound control, nine patients received a complementary injection. At each follow-up, overall patient satisfaction was high and was validated by clearance of rhytids, veins, bony prominences, and dermal and subcutaneous atrophy. Conclusion Skin revitalization with injectable HA can improve the clinical appearance of the back of the hands. However, this therapy requires knowledge of the possible complications and their remediation as well as knowledge and respect of injected doses. Moreover, despite excellent results at each follow-up, the results of our series are not as good after 6 months, and a longer follow-up would be needed to determine if this procedure provides long-lasting benefit.

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In Vivo Stimulation of De Novo Collagen Production Caused by Cross-linked Hyaluronic Acid Dermal Filler Injections in Photodamaged Human Skin

Cited by 405 publications

References 41 publications

Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin

Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin

Lower periorbital area treatment with Restylane Vital Skinbooster

Nonanimal Stabilized Hyaluronic Acid for Tissue Augmentation of the Dorsal Hands: A Prospective Study on 38 Patients

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