Widgerow Alan D, Ziegler Mary E, Shafiq Faiza
Division Chief Research, Professor Plastic Surgery Center for Tissue Engineering, University of California, Irvine, California, USA.
Alastin a Galderma Company, Fort Worth, Texas, USA.
J Cosmet Dermatol. 2025 Feb;24(2):e16690. doi: 10.1111/jocd.16690. Epub 2024 Dec 11.
The original TriHex combination-Tripeptide-1 and Hexapeptide-12 (TriHex) encompasses a peptide combination selected for its ability to modulate the extracellular matrix (ECM) by progressively eliminating clumped collagen and elastin fragments and then stimulating replacement with new collagen and elastin. Incorporation of a proprietary, patent-pending Octapeptide-45 (Octa) to the TriHex original provides potential for added benefit based on the peptide's capacity to stimulate hyaluronic acid (HA) and its anticipated added benefit in wound healing. This is named TriHex 2.0 in the paper.
A full-scale validation process was structured to assess Octa synergy with TriHex using an ex vivo model, assessing ECM changes histologically in relation to elastin, HA and basement membrane components. In addition, gene expression studies were undertaken, including bulk and single cell sequencing analysis to assess the particular changes that occurred by adding Octa to the TriHex. Following the gene expression analysis, a further round of ex vivo studies was conducted to assess protein expression of the defined differentially expressed genes using histological staining.
Octa synergized with TriHex as demonstrated by significantly upregulated genes (p < 0.05) affecting the ECM and basement membrane. A histological assessment using the ex vivo model demonstrated tropoelastin intensity significantly increasing with TriHex (43%) and 2.0 (42%) (p < 0.05 for both) compared to untreated explants. HA levels (CD44 intensity) significantly increased with TriHex (69%; p < 0.01), while TriHex 2.0 demonstrated HA levels 160% greater (p < 0.001) than the untreated tissue. Single cell sequencing identified a gene expression profile upregulation relating to ECM modulation and wound healing in both TriHex and 2.0, but TriHex 2.0 showed additional activities in basement membrane physiology, stem cell recruitment, and protection of fibroblasts against cellular senescence.
The addition of Octapeptide-45 to TriHex technology in the form of TriHex 2.0 is a significant advance to TriHex technology science. Both forms demonstrate ECM remodeling and positive wound healing, but supplementary benefits are evident including increased elastin and hyaluronic acid stimulation, added effects on the basement membrane, additional wound healing capacity in basal keratinocytes and anti-senescent effects in fibroblasts. This is helpful for pre-conditioning of the skin prior to procedures and post procedure related to additional ECM remodeling, wound healing advantages, senescent cell targeting and DEJ strengthening. Clinical studies to follow.
最初的TriHex组合——三肽-1和六肽-12（TriHex）包含一种肽组合，因其能够通过逐步清除聚集的胶原蛋白和弹性蛋白片段，然后刺激新的胶原蛋白和弹性蛋白的替代，从而调节细胞外基质（ECM）而被选中。在TriHex原有成分中加入一种正在申请专利的专有八肽-45（Octa），基于该肽刺激透明质酸（HA）的能力及其在伤口愈合方面预期的额外益处，有可能带来更多益处。本文中将其命名为TriHex 2.0。
构建了一个全面的验证过程，使用体外模型评估Octa与TriHex的协同作用，通过组织学方法评估与弹性蛋白、HA和基底膜成分相关的ECM变化。此外，还进行了基因表达研究，包括大量和单细胞测序分析，以评估在TriHex中添加Octa后发生的特定变化。在基因表达分析之后，又进行了一轮体外研究，使用组织学染色评估已确定的差异表达基因的蛋白质表达。
Octa与TriHex协同作用，表现为影响ECM和基底膜的基因显著上调（p < 0.05）。使用体外模型进行的组织学评估表明，与未处理的外植体相比，原弹性蛋白强度在TriHex组（43%）和2.0组（42%）中均显著增加（两者p < 0.05）。HA水平（CD44强度）在TriHex组显著增加（69%；p < 0.01），而TriHex 2.0组的HA水平比未处理组织高160%（p < 0.001）。单细胞测序确定了TriHex和2.0中与ECM调节和伤口愈合相关的基因表达谱上调，但TriHex 2.0在基底膜生理学、干细胞募集以及保护成纤维细胞免受细胞衰老方面表现出额外的活性。
以TriHex 2.0的形式在TriHex技术中添加八肽-45是TriHex技术科学的一项重大进展。两种形式都显示出ECM重塑和积极的伤口愈合作用，但额外的益处也很明显，包括增加对弹性蛋白和透明质酸的刺激、对基底膜的附加作用、对基底角质形成细胞额外的伤口愈合能力以及对成纤维细胞的抗衰老作用。这有助于在与额外的ECM重塑、伤口愈合优势、衰老细胞靶向和真皮表皮连接强化相关的手术前和手术后对皮肤进行预处理。后续将开展临床研究。
