Hyaluronic acid-cross-linked filler stimulates collagen type 1 and elastic fiber synthesis in skin through the TGF-β/Smad signaling pathway in a nude mouse model

Yingfang Fan, Tae Hyun Choi, Jee Hyeok Chung, Yoon Kyung Jeon, Suk Wha Kim

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Compared to pure hyaluronic acid filler, cross-linked hyaluronic acid (HAc) exhibits superior biocompatibility and longevity as a dermal filler. We previously developed composite HAc-hydroxyapatite (HAp) fillers. Herein, we systematically compared the protein-level increase and gene expression between HAc-micro-HAp and HAc-nano-HAp in mice and determined the mechanisms underlying the biological responses to HAc and HAp. Five-week-old female BALB/c-nude mice were classified into five groups: normal skin, Radiesse, Restylane, HAc-nano-HAp, and HAc-micro-HAp. Fillers (200 μl) were injected to evenly fill the back of mice. Skin biopsies were performed to investigate collagen and elastic fiber synthesis after filler injections. Western blot analysis, real-time polymerase chain reaction analysis, and immunohistochemistry were performed to investigate protein and gene expression changes. Organ (liver, lung, spleen, and kidney) toxicity of HAc-nano-HAp was determined by hematoxylin and eosin staining after 12 weeks. Protein and gene expression analyses indicated that, compared with pure fillers, HAc-nano-HAp and HAc-micro-HAp hydrogels preferentially promoted collagen and elastic fiber formation through the TGF-β pathway. The composite fillers also exhibited no evidence of organ toxicity. HAc–HAp filler might play an important role in collagen and elastic fiber regeneration. HAc filler stimulates collagen type 1 and elastic fiber synthesis through the TGF-β/Smad pathway. The role of HAc–HAp composite fillers in photoaging in animal models and their effects on skin, including elasticity and tensile strength, should be investigated.

Original languageEnglish
Pages (from-to)1355-1362
Number of pages8
JournalJournal of Plastic, Reconstructive and Aesthetic Surgery
Volume72
Issue number8
DOIs
StatePublished - 1 Aug 2019

Fingerprint

Elastic Tissue
Hyaluronic Acid
Collagen Type I
Nude Mice
Durapatite
Skin
Collagen
Gene Expression
Proteins
Hydrogels
Tensile Strength
Elasticity
Hematoxylin
Eosine Yellowish-(YS)
Real-Time Polymerase Chain Reaction
Regeneration
Spleen
Animal Models
Western Blotting
Immunohistochemistry

Keywords

  • Collagen type 1
  • Dermal filler
  • Elastic fiber
  • HAc-micro-HAp
  • HAc-nano-HAp
  • TGF-β/Smad pathway

Cite this

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title = "Hyaluronic acid-cross-linked filler stimulates collagen type 1 and elastic fiber synthesis in skin through the TGF-β/Smad signaling pathway in a nude mouse model",
abstract = "Compared to pure hyaluronic acid filler, cross-linked hyaluronic acid (HAc) exhibits superior biocompatibility and longevity as a dermal filler. We previously developed composite HAc-hydroxyapatite (HAp) fillers. Herein, we systematically compared the protein-level increase and gene expression between HAc-micro-HAp and HAc-nano-HAp in mice and determined the mechanisms underlying the biological responses to HAc and HAp. Five-week-old female BALB/c-nude mice were classified into five groups: normal skin, Radiesse, Restylane, HAc-nano-HAp, and HAc-micro-HAp. Fillers (200 μl) were injected to evenly fill the back of mice. Skin biopsies were performed to investigate collagen and elastic fiber synthesis after filler injections. Western blot analysis, real-time polymerase chain reaction analysis, and immunohistochemistry were performed to investigate protein and gene expression changes. Organ (liver, lung, spleen, and kidney) toxicity of HAc-nano-HAp was determined by hematoxylin and eosin staining after 12 weeks. Protein and gene expression analyses indicated that, compared with pure fillers, HAc-nano-HAp and HAc-micro-HAp hydrogels preferentially promoted collagen and elastic fiber formation through the TGF-β pathway. The composite fillers also exhibited no evidence of organ toxicity. HAc–HAp filler might play an important role in collagen and elastic fiber regeneration. HAc filler stimulates collagen type 1 and elastic fiber synthesis through the TGF-β/Smad pathway. The role of HAc–HAp composite fillers in photoaging in animal models and their effects on skin, including elasticity and tensile strength, should be investigated.",
keywords = "Collagen type 1, Dermal filler, Elastic fiber, HAc-micro-HAp, HAc-nano-HAp, TGF-β/Smad pathway",
author = "Yingfang Fan and Choi, {Tae Hyun} and Chung, {Jee Hyeok} and Jeon, {Yoon Kyung} and Kim, {Suk Wha}",
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T1 - Hyaluronic acid-cross-linked filler stimulates collagen type 1 and elastic fiber synthesis in skin through the TGF-β/Smad signaling pathway in a nude mouse model

AU - Fan, Yingfang

AU - Choi, Tae Hyun

AU - Chung, Jee Hyeok

AU - Jeon, Yoon Kyung

AU - Kim, Suk Wha

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Compared to pure hyaluronic acid filler, cross-linked hyaluronic acid (HAc) exhibits superior biocompatibility and longevity as a dermal filler. We previously developed composite HAc-hydroxyapatite (HAp) fillers. Herein, we systematically compared the protein-level increase and gene expression between HAc-micro-HAp and HAc-nano-HAp in mice and determined the mechanisms underlying the biological responses to HAc and HAp. Five-week-old female BALB/c-nude mice were classified into five groups: normal skin, Radiesse, Restylane, HAc-nano-HAp, and HAc-micro-HAp. Fillers (200 μl) were injected to evenly fill the back of mice. Skin biopsies were performed to investigate collagen and elastic fiber synthesis after filler injections. Western blot analysis, real-time polymerase chain reaction analysis, and immunohistochemistry were performed to investigate protein and gene expression changes. Organ (liver, lung, spleen, and kidney) toxicity of HAc-nano-HAp was determined by hematoxylin and eosin staining after 12 weeks. Protein and gene expression analyses indicated that, compared with pure fillers, HAc-nano-HAp and HAc-micro-HAp hydrogels preferentially promoted collagen and elastic fiber formation through the TGF-β pathway. The composite fillers also exhibited no evidence of organ toxicity. HAc–HAp filler might play an important role in collagen and elastic fiber regeneration. HAc filler stimulates collagen type 1 and elastic fiber synthesis through the TGF-β/Smad pathway. The role of HAc–HAp composite fillers in photoaging in animal models and their effects on skin, including elasticity and tensile strength, should be investigated.

AB - Compared to pure hyaluronic acid filler, cross-linked hyaluronic acid (HAc) exhibits superior biocompatibility and longevity as a dermal filler. We previously developed composite HAc-hydroxyapatite (HAp) fillers. Herein, we systematically compared the protein-level increase and gene expression between HAc-micro-HAp and HAc-nano-HAp in mice and determined the mechanisms underlying the biological responses to HAc and HAp. Five-week-old female BALB/c-nude mice were classified into five groups: normal skin, Radiesse, Restylane, HAc-nano-HAp, and HAc-micro-HAp. Fillers (200 μl) were injected to evenly fill the back of mice. Skin biopsies were performed to investigate collagen and elastic fiber synthesis after filler injections. Western blot analysis, real-time polymerase chain reaction analysis, and immunohistochemistry were performed to investigate protein and gene expression changes. Organ (liver, lung, spleen, and kidney) toxicity of HAc-nano-HAp was determined by hematoxylin and eosin staining after 12 weeks. Protein and gene expression analyses indicated that, compared with pure fillers, HAc-nano-HAp and HAc-micro-HAp hydrogels preferentially promoted collagen and elastic fiber formation through the TGF-β pathway. The composite fillers also exhibited no evidence of organ toxicity. HAc–HAp filler might play an important role in collagen and elastic fiber regeneration. HAc filler stimulates collagen type 1 and elastic fiber synthesis through the TGF-β/Smad pathway. The role of HAc–HAp composite fillers in photoaging in animal models and their effects on skin, including elasticity and tensile strength, should be investigated.

KW - Collagen type 1

KW - Dermal filler

KW - Elastic fiber

KW - HAc-micro-HAp

KW - HAc-nano-HAp

KW - TGF-β/Smad pathway

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U2 - 10.1016/j.bjps.2019.03.032

DO - 10.1016/j.bjps.2019.03.032

M3 - Article

VL - 72

SP - 1355

EP - 1362

JO - Journal of Plastic, Reconstructive and Aesthetic Surgery

JF - Journal of Plastic, Reconstructive and Aesthetic Surgery

SN - 1748-6815

IS - 8

ER -