Transcutaneous implantation of valproic acid-encapsulated dissolving microneedles induces hair regrowth

Shayan Fakhraei Lahiji, Seol Hwa Seo, Suyong Kim, Manita Dangol, Jiyong Shim, Cheng Guo Li, Yonghao Ma, Chisong Lee, Geonwoo Kang, Huisuk Yang, Kang Yell Choi, Hyungil Jung

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The interest in alternative material systems and delivery methods for treatment of androgenetic alopecia has been increasing in the recent decades. Topical application of valproic acid (VPA), an FDA-approved anticonvulsant drug, has been shown to effectively stimulate hair follicle (HF) regrowth by upregulating Wnt/β-catenin, a key pathway involved in initiation of HF development. Moreover, a majority of studies have suggested that cutaneous wound re-epithelialization is capable of inducing HF through Wnt/β-catenin pathway. Here, we report fabrication and evaluation of a novel VPA-encapsulating dissolving microneedle (DMN-VPA) that creates minimally invasive dermal micro-wounds upon application, significantly improving the VPA delivery efficiency. DMN-VPA not only delivers encapsulated VPA with higher accuracy than topical application, it also stimulates wound re-epithelialization signals involved in HF regrowth. Through a series of in vivo studies, we show that micro-wounding-mediated implantation of DMN-VPA upregulates expression of Wnt/β-catenin pathway, alkaline phosphatase, proliferating cell nuclear antigen, loricrin and HF stem cell markers, including keratin 15, and CD34 more effectively than topical application.

Original languageEnglish
Pages (from-to)69-79
Number of pages11
JournalBiomaterials
Volume167
DOIs
Publication statusPublished - 2018 Jun

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Valproic Acid
Hair Follicle
Re-Epithelialization
Acids
Catenins
Wnt Signaling Pathway
Keratin-15
Keratin
Skin
Alopecia
Phosphatases
Proliferating Cell Nuclear Antigen
Antigens
Stem cells
Anticonvulsants
Alkaline Phosphatase
Up-Regulation
Stem Cells
Fabrication
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Fakhraei Lahiji, Shayan ; Seo, Seol Hwa ; Kim, Suyong ; Dangol, Manita ; Shim, Jiyong ; Li, Cheng Guo ; Ma, Yonghao ; Lee, Chisong ; Kang, Geonwoo ; Yang, Huisuk ; Choi, Kang Yell ; Jung, Hyungil. / Transcutaneous implantation of valproic acid-encapsulated dissolving microneedles induces hair regrowth. In: Biomaterials. 2018 ; Vol. 167. pp. 69-79.
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abstract = "The interest in alternative material systems and delivery methods for treatment of androgenetic alopecia has been increasing in the recent decades. Topical application of valproic acid (VPA), an FDA-approved anticonvulsant drug, has been shown to effectively stimulate hair follicle (HF) regrowth by upregulating Wnt/β-catenin, a key pathway involved in initiation of HF development. Moreover, a majority of studies have suggested that cutaneous wound re-epithelialization is capable of inducing HF through Wnt/β-catenin pathway. Here, we report fabrication and evaluation of a novel VPA-encapsulating dissolving microneedle (DMN-VPA) that creates minimally invasive dermal micro-wounds upon application, significantly improving the VPA delivery efficiency. DMN-VPA not only delivers encapsulated VPA with higher accuracy than topical application, it also stimulates wound re-epithelialization signals involved in HF regrowth. Through a series of in vivo studies, we show that micro-wounding-mediated implantation of DMN-VPA upregulates expression of Wnt/β-catenin pathway, alkaline phosphatase, proliferating cell nuclear antigen, loricrin and HF stem cell markers, including keratin 15, and CD34 more effectively than topical application.",
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Fakhraei Lahiji, S, Seo, SH, Kim, S, Dangol, M, Shim, J, Li, CG, Ma, Y, Lee, C, Kang, G, Yang, H, Choi, KY & Jung, H 2018, 'Transcutaneous implantation of valproic acid-encapsulated dissolving microneedles induces hair regrowth', Biomaterials, vol. 167, pp. 69-79. https://doi.org/10.1016/j.biomaterials.2018.03.019

Transcutaneous implantation of valproic acid-encapsulated dissolving microneedles induces hair regrowth. / Fakhraei Lahiji, Shayan; Seo, Seol Hwa; Kim, Suyong; Dangol, Manita; Shim, Jiyong; Li, Cheng Guo; Ma, Yonghao; Lee, Chisong; Kang, Geonwoo; Yang, Huisuk; Choi, Kang Yell; Jung, Hyungil.

In: Biomaterials, Vol. 167, 06.2018, p. 69-79.

Research output: Contribution to journalArticle

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T1 - Transcutaneous implantation of valproic acid-encapsulated dissolving microneedles induces hair regrowth

AU - Fakhraei Lahiji, Shayan

AU - Seo, Seol Hwa

AU - Kim, Suyong

AU - Dangol, Manita

AU - Shim, Jiyong

AU - Li, Cheng Guo

AU - Ma, Yonghao

AU - Lee, Chisong

AU - Kang, Geonwoo

AU - Yang, Huisuk

AU - Choi, Kang Yell

AU - Jung, Hyungil

PY - 2018/6

Y1 - 2018/6

N2 - The interest in alternative material systems and delivery methods for treatment of androgenetic alopecia has been increasing in the recent decades. Topical application of valproic acid (VPA), an FDA-approved anticonvulsant drug, has been shown to effectively stimulate hair follicle (HF) regrowth by upregulating Wnt/β-catenin, a key pathway involved in initiation of HF development. Moreover, a majority of studies have suggested that cutaneous wound re-epithelialization is capable of inducing HF through Wnt/β-catenin pathway. Here, we report fabrication and evaluation of a novel VPA-encapsulating dissolving microneedle (DMN-VPA) that creates minimally invasive dermal micro-wounds upon application, significantly improving the VPA delivery efficiency. DMN-VPA not only delivers encapsulated VPA with higher accuracy than topical application, it also stimulates wound re-epithelialization signals involved in HF regrowth. Through a series of in vivo studies, we show that micro-wounding-mediated implantation of DMN-VPA upregulates expression of Wnt/β-catenin pathway, alkaline phosphatase, proliferating cell nuclear antigen, loricrin and HF stem cell markers, including keratin 15, and CD34 more effectively than topical application.

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