兰州大学机构库 >化学化工学院
迷你胶原蛋白的设计及其在光损伤皮肤修复中的应用
Alternative TitleConstruction of mini collagen and its application in the healing of photodamaged skin
Shuangni Shi
Subtype硕士
Thesis Advisor肖建喜
2023-08-31
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name工学硕士
Degree Discipline材料与化工
Keyword胶原蛋白 collagen 迷你胶原蛋白 Mini Collagen 透皮性能 transdermal properties 光损伤皮肤 photodamaged skin 皮肤损伤修复 skin damage repair
Abstract

皮肤是人体最大的器官,是人体与外界环境的第一道防线。皮肤过度暴露于紫外线辐射导致的不同程度的损伤,是21世纪最严重的公共卫生问题之一。胶原蛋白是皮肤真皮层的主要成分,能够维持组织和器官的机械强度及结构完整性,参与调节各种细胞活动,在皮肤修复领域备受关注。目前,胶原蛋白主要来源于动物组织提取。但动物源三螺旋胶原蛋白存在免疫原性、病毒传播隐患和难以透过皮肤的问题。而水解胶原多肽氨基酸序列随机且不具有三螺旋结构。因此,构建序列可控且具有良好生物相容性和生物活性的胶原蛋白仿生材料一直是皮肤医学等领域的研究热点。固相合成的胶原蛋白仿生多肽氨基酸序列可控、无病毒传播隐患和免疫原性。因此,本论文旨在设计构建一系列仿生天然胶原蛋白结构和功能的胶原蛋白仿生多肽(又被称为迷你胶原蛋白),并研究其在皮肤损伤修复领域的应用,主要研究内容如下: 1.模拟天然胶原蛋白组成、结构和功能的仿生材料,在皮肤损伤修复中具有重要意义。我们设计并合成了一系列具有三螺旋结构和功能序列的高活性迷你胶原蛋白。所设计的迷你胶原蛋白由两端重复的Gly-Pro-Hyp序列和中间天然胶原蛋白的功能序列GFOGER组成。迷你胶原蛋白具有稳定的三螺旋结构和良好的细胞相容性。只有同时具有三螺旋结构和功能序列的迷你胶原蛋白,能够促进成纤维细胞的粘附和迁移。该迷你胶原蛋白能够快速恢复紫外光损伤皮肤的密度、色度和水分。动物实验表明,该体系迷你胶原蛋白显著刺激胶原蛋白再生,有效促进光损伤皮肤修复,在组织再生和皮肤医学领域具有潜在的应用价值。 2.皮肤的屏障作用严重限制了多肽、蛋白质等功能大分子的透皮递送效率和功效发挥。因此,开发具有透皮性能的迷你胶原蛋白至关重要。我们首次构建了一系列含有精氨酸的透皮迷你胶原蛋白,筛选出具有高效透皮性能和促进皮肤损伤修复能力的透皮迷你胶原蛋白,以改善迷你胶原蛋白的透皮性能和皮肤修复能力。我们设计的透皮迷你胶原蛋白具有稳定的三螺旋结构和优良的生物相容性,能够促进成纤维细胞的增殖和粘附。透皮迷你胶原蛋白具有良好的透细胞和透皮能力,能够显著促进急性紫外损伤皮肤的修复,其效果优于迷你胶原蛋白。本工作构建的透皮迷你胶原蛋白能够有效穿透皮肤,并实现损伤皮肤的自修复,为后续在功效护肤品领域的应用奠定了坚实的基础。 3.目前护肤品中的胶原蛋白主要来自于动物组织提取,但动物源胶原蛋白存在稳定性差或生物活性差的问题。我们在工作二透皮迷你胶原蛋白的基础上,首次开发了一款透皮迷你胶原蛋白修复敷料产品。我们研发的透皮迷你胶原蛋白敷料产品具有良好的稳定性,在广泛的温度范围内都不发生聚沉。动物实验表明,相较于市售胶原蛋白敷料产品,我们开发的透皮迷你胶原蛋白敷料能够快速恢复皮肤的密度、亮度和水分,显著促进急性紫外损伤皮肤的修复。志愿者的不良反应反馈、感官评价、客观评价和主观评价等实验结果表明,我们开发的透皮迷你胶原蛋白敷料使用感良好且能够有效改善皮肤状态。因此,我们开发的透皮迷你胶原蛋白敷料产品将在功效护肤品领域具有广阔的市场前景。

Other Abstract

The skin is the largest organ of the human body serving as the first line of defense between the human body and the external environment. Skin damage caused by prolonged exposure to ultraviolet radiation is considered one of the most severe public health issues of the 21st century. Collagen is the primary component of the dermis of the skin, able to maintain the mechanical strength and structural integrity of tissues and organs. It actively participates in regulating various cellular activities and has garnered significant attention in the field of skin repair. Currently, collagen is mainly extracted from animal tissues. However, animal-derived triple helix collagen poses some problems such as immunogenicity, potential virus transmission and difficulty in penetrating the skin. The amino acid sequence of hydrolyzed collagen peptides is random and lacks the triple helix structure. Therefore, the construction of sequence-controlled collagen mimetic materials with superior biocompatibility and bioactivity has been a research hotspot in the field of dermatology. The amino acid sequence of collagen mimetic pepetides synthesized by solid phase is controllable, and there is no risk of virus transmission and immunogenicity.Thus, this thesis aims to design and construct a series of collagen mimetic pepetides (also named as Mini Collagen) that mimic the structure and function of natural collagen and to investigate their applications in the healing of photodamaged skin. The main contents are as follows:

1. The construction of biomimetic materials that mimic the composition, structure, and function of natural collagen has significant importance in repairing damaged skin. We have designed and synthesized a series of highly active Mini Collagen with triple-helical structures and functional sequences. The designed Mini Collagen consists of the repeating Gly-Pro-Hyp sequence at the N-/C- terminals and the central functional sequence GFOGER derived from natural collagen. Mini Collagen displays a stable triple helix structure and exceptional biocompatibility. Only Mini Collagen that simultaneously possesses both the triple helical structure and functional sequences can promote fibroblast adhesion and migration. The Mini Collagen has the ability to rapidly recover the density, color, and moisture of UV-damaged skin. Animal experiment results have demonstrated that this Mini Collagen significantly stimulates collagen regeneration and effectively promotes the repair of photodamaged skin. It has potential application in the fields of tissue regeneration and dermatology.

2. The barrier effect of the skin severely limits the transdermal delivery efficiency of functional macromolecules such as peptides and proteins. Therefore, the development of Mini Collagen with transdermal properties is crucial. We have for the first time constructed a series of arginine-containing transdermal Mini Collagen and selected a transdermal Mini Collagen with highly efficient transdermal properties and the ability to promote photodamaged skin repair, which improves the transdermal properties of Mini Collagen and the ability of skin repair. We designed transdermal Mini Collagen that exhibited a stable triple helical structure and excellent biocompatibility, which can promote the proliferation and adhesion of fibroblast. Transdermal Mini Collagen has good transcellular and transdermal ability, and can significantly promote the repair of acute UV-damaged skin, which is superior to that of Mini Collagen. The transdermal Mini Collagen constructed in this work demonstrates effective skin penetration and facilitates the self-repair of damaged skin. These findings establish a solid foundation for their future applications in the functional cosmetics industry.

3. Collagen used in skin-care products is mainly extracted from animal tissues. However, animal-derived collagen poses challenges in terms of stability or biological activity. For the first time, we have developed a transdermal Mini Collagen repair dressing based on the second work. The transdermal Mini Collagen dressing exhibits excellent stability and does not aggregate over a wide range of temperatures. Animal studies have shown that compared to commercial collagen dressing products, the transdermal Mini Collagen dressing can rapidly recover skin density, color, and moisture and significantly promote the repair of acute UV-damaged skin. The experimental results of adverse reaction feedback, sensory evaluation, objective evaluation, and subjective evaluation of volunteers indicate that the transdermal Mini Collagen dressing has excellent user feelings and effectively improves skin condition. Therefore, our transdermal Mini Collagen dressing product will have a broad market prospect in the field of efficacy skin-care products.

MOST Discipline Catalogue工学 - 材料与化工
URL查看原文
Language中文
Other Code262010_220200921940
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/538071
Collection化学化工学院
Affiliation
兰州大学化学化工学院
Recommended Citation
GB/T 7714
Shuangni Shi. 迷你胶原蛋白的设计及其在光损伤皮肤修复中的应用[D]. 兰州. 兰州大学,2023.
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