A New World of Anti-aging Skincare Targeting the Face-Wrapping “Tensional Network”: “Ring-Collagen”
-Paradigm Shift of Skin Analysis: From Visualizing Tangible to Intangible Targets-
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Presented by: Tomonobu Ezure
Introduction:
Facial skin tightly “wraps” internal structures to retain facial morphology via tension. Loss of this tension loosens the skin, leading to sagging and wrinkles, namely aged appearance. However, the mechanisms that regulate skin tension remain unclear, because when skin is excised, it loses tension. Further, there is no way to visualize intangible skin tension.
Objectives:
Our aims were: 1) to establish visualization technology of skin tension, then 2) use it to clarify the mechanism of skin tension regulation, and based on this, 3) to establish novel solutions to improve aged appearance.
Methods:
137 facial skin specimens were analyzed. Non-invasive skin analysis and efficacy testing were conducted with 30 and 16 female volunteers, respectively.
Results:
1. Reconstruction of 4D skin tensional dynamics in real space: “skin-mechanics reality”
Skin specimens contract immediately after excision. Thus, we reconstructed skin tension by stretching specimens to their pre-dissected size using a micro-manipulator. The tensioned skin samples were deformed and observed by X-ray micro-CT, followed by artificial intelligence-based tracking of structures to analyze the tension. Then, tensional dynamics in millions of areas was digitally reconstructed in real space using newly established autostereoscopy software. This enables us to recognize complex spatiotemporal tensional dynamics by operating and monitoring a stereoscopic object in real space. Furthermore, since the skin is digitally reconstructed, we can digitally dissect and isolate skin components during deformation while visualizing tension with colors and vectors (see movies in the presentation). We called this off-screen visualization technology for intangible properties “skin-mechanics reality”.
2. “Ring-collagen” surrounding fine hairs produces skin tension to retain facial morphology
Skin-mechanics reality viewing revealed that horizontal circular areas of high tension exist in the dermal layer. Component analysis revealed that these ring-shaped areas consisted of high-density collagen fibers, and they each surrounded a thick low-tension proteoglycan layer with a fine (vellus) hair at the center. Notably, these ring-shaped collagen structures showed centrally directed tension. Since fine hairs existed at high density in facial skin, huge numbers of ring-shaped collagens formed honeycomb-like structure, producing a large overall skin “tensional network”.
These ring-shaped collagen structures significantly decreased with aging. Furthermore, noninvasive measurement of female cheek skin revealed that loss of the structures significantly decreased skin tension and worsened sagging. Therefore, these novel circular collagen structures produce skin tension, enabling the skin to tightly wrap around understructures, thus serving as a facial anti-deformation system. We designate them “ring-collagen”.
3. Ring-collagen regulates skin tension in response to environmental conditions via fine hair, and stimulation of fine hairs improves aged facial appearance
To investigate the mechanism of ring-collagen formation, we established a co-culture model of ring-collagen formation. We found that hair (outer root sheath; ORS) cells induced production of proteoglycans by surrounding cells (fibroblasts). Further, ORS highly expressed Wnt16 in histological RNA-seq analysis, and Wnt16 itself increased proteoglycans in fibroblasts. Thus, fine hairs induce production of proteoglycans from surrounding cells via Wnt16, and these proteoglycans displace and compact adjacent collagen to form the ring-collagen structures.
Interestingly, environmental stimulation of fine hairs either thermally (heat) or physically (extra tension) strengthened ring-collagen in an organ-culture system via the above Wnt16-proteoglycan pathway. Indeed, these stimulations increased skin tension and improved cheek sagging in volunteers, with no increase of fine hairs. Collectively, ring-collagen regulates skin tension in response to environmental conditions via fine hair. Thus, ring-collagen is an emerging target for anti-aging skincare, accessible via stimulation of fine hair.
Conclusion:
We established novel skin analysis technology, “skin-mechanics reality”, which represents a paradigm shift in skin analysis, enabling visualization of intangible properties (physical dynamics) in real space, rather than just tangible structures. This technology revealed “ring-collagen”, which produces a skin “tensional network” to tightly “wrap” the face and retain its morphology, acting as an anti-deformation system. We also clarified that ring-collagen controls skin tension in response to environmental conditions via fine hair, so environmental stimulations of fine hairs improve aged appearance. These discoveries drastically change the “commonsense” aesthetic view of fine hair; instead of an unsightly blemish, it is a key target of skincare, leading to various novel solutions based on environmental approaches (devices, beauty treatments, base materials and drugs). We believe our “skin-mechanics reality” technology, discovery of “ring-collagen”, and commonsense-changing target “fine hair” open up a new world of skincare.
Facial skin tightly “wraps” internal structures to retain facial morphology via tension. Loss of this tension loosens the skin, leading to sagging and wrinkles, namely aged appearance. However, the mechanisms that regulate skin tension remain unclear, because when skin is excised, it loses tension. Further, there is no way to visualize intangible skin tension.
Objectives:
Our aims were: 1) to establish visualization technology of skin tension, then 2) use it to clarify the mechanism of skin tension regulation, and based on this, 3) to establish novel solutions to improve aged appearance.
Methods:
137 facial skin specimens were analyzed. Non-invasive skin analysis and efficacy testing were conducted with 30 and 16 female volunteers, respectively.
Results:
1. Reconstruction of 4D skin tensional dynamics in real space: “skin-mechanics reality”
Skin specimens contract immediately after excision. Thus, we reconstructed skin tension by stretching specimens to their pre-dissected size using a micro-manipulator. The tensioned skin samples were deformed and observed by X-ray micro-CT, followed by artificial intelligence-based tracking of structures to analyze the tension. Then, tensional dynamics in millions of areas was digitally reconstructed in real space using newly established autostereoscopy software. This enables us to recognize complex spatiotemporal tensional dynamics by operating and monitoring a stereoscopic object in real space. Furthermore, since the skin is digitally reconstructed, we can digitally dissect and isolate skin components during deformation while visualizing tension with colors and vectors (see movies in the presentation). We called this off-screen visualization technology for intangible properties “skin-mechanics reality”.
2. “Ring-collagen” surrounding fine hairs produces skin tension to retain facial morphology
Skin-mechanics reality viewing revealed that horizontal circular areas of high tension exist in the dermal layer. Component analysis revealed that these ring-shaped areas consisted of high-density collagen fibers, and they each surrounded a thick low-tension proteoglycan layer with a fine (vellus) hair at the center. Notably, these ring-shaped collagen structures showed centrally directed tension. Since fine hairs existed at high density in facial skin, huge numbers of ring-shaped collagens formed honeycomb-like structure, producing a large overall skin “tensional network”.
These ring-shaped collagen structures significantly decreased with aging. Furthermore, noninvasive measurement of female cheek skin revealed that loss of the structures significantly decreased skin tension and worsened sagging. Therefore, these novel circular collagen structures produce skin tension, enabling the skin to tightly wrap around understructures, thus serving as a facial anti-deformation system. We designate them “ring-collagen”.
3. Ring-collagen regulates skin tension in response to environmental conditions via fine hair, and stimulation of fine hairs improves aged facial appearance
To investigate the mechanism of ring-collagen formation, we established a co-culture model of ring-collagen formation. We found that hair (outer root sheath; ORS) cells induced production of proteoglycans by surrounding cells (fibroblasts). Further, ORS highly expressed Wnt16 in histological RNA-seq analysis, and Wnt16 itself increased proteoglycans in fibroblasts. Thus, fine hairs induce production of proteoglycans from surrounding cells via Wnt16, and these proteoglycans displace and compact adjacent collagen to form the ring-collagen structures.
Interestingly, environmental stimulation of fine hairs either thermally (heat) or physically (extra tension) strengthened ring-collagen in an organ-culture system via the above Wnt16-proteoglycan pathway. Indeed, these stimulations increased skin tension and improved cheek sagging in volunteers, with no increase of fine hairs. Collectively, ring-collagen regulates skin tension in response to environmental conditions via fine hair. Thus, ring-collagen is an emerging target for anti-aging skincare, accessible via stimulation of fine hair.
Conclusion:
We established novel skin analysis technology, “skin-mechanics reality”, which represents a paradigm shift in skin analysis, enabling visualization of intangible properties (physical dynamics) in real space, rather than just tangible structures. This technology revealed “ring-collagen”, which produces a skin “tensional network” to tightly “wrap” the face and retain its morphology, acting as an anti-deformation system. We also clarified that ring-collagen controls skin tension in response to environmental conditions via fine hair, so environmental stimulations of fine hairs improve aged appearance. These discoveries drastically change the “commonsense” aesthetic view of fine hair; instead of an unsightly blemish, it is a key target of skincare, leading to various novel solutions based on environmental approaches (devices, beauty treatments, base materials and drugs). We believe our “skin-mechanics reality” technology, discovery of “ring-collagen”, and commonsense-changing target “fine hair” open up a new world of skincare.