皮肤模型与微针穿刺性能评价的研究

微针阵列作为新型透皮给药技术，受到广泛关注。通常以刺入力、刺入率和刺入深度来评价微针刺入皮肤的程度和效率。皮肤是其性能评价的基础。皮肤的物理特性主要由角蛋白丝、胶原纤维、弹性纤维和皮下组织综合决定，并且从厚度、弹性、硬度和韧性等维度反映其对微针刺入的影响。机械的、渗透的、组织的和屏障的等皮肤模型被用于解读和模拟真实皮肤的该方面功能。同样，通过皮肤力学分析后建立的包括本构模型在内的各种皮肤力学模型也从物理维度解析皮肤的力学特征。真实皮肤具有复杂性，存在差异性大、不易获取和储存，以及伦理等问题，而皮肤模型可在一定程度上代替真实皮肤辅助微针递送系统设计、开发和性能评价。本文系统回顾分析了皮肤组织的物理特性、各种皮肤模型的制备及特点、真实皮肤和模拟皮肤在评价微针穿刺性能方面的应用，为开发及建立合适的皮肤模型提供借鉴。

Skin Models and Its Related Evaluation of Microneedle Puncture Performance

The force, speed and depth of microneedle array penetration process are usually used to evaluate the degree and efficiency of its penetration into the skin.The skin is the basis of its performance evaluation. The physical properties of the skin are mainly determined by the combination of keratin filaments, collagen fibers, elastic fibers and subcutaneous tissues, and reflect its impact on microneedle penetration from dimensions such as thickness, elasticity, hardness and toughness. Mechanical, permeable, tissue and barrier skin models are used to explain and simulate this aspect of real skin functions. Similarly, various skin mechanics models including constitutive models established after skin mechanics analysis also analyze the mechanical characteristics of the skin from the physical dimension. Real skin is complicated, with large differences, difficult access and storage, and some ethical issues. Skin model can replace real skin assisted to a certain extent for the design, development and performance evaluation of microneedle delivery system. The material involved in the model may be different from the physical properties of the real skin, it cannot fully simulate the chemical composition and distribution of the real skin, the tissue structure, and the interaction between the skin tissue and other tissues. However, the skin model can be easily adjusted by changing those characteristic materials comparable to the skin and form a simulation system. As for microneedle evaluation, it is more necessary to consider the mechanical properties of the skin and the skin model. The skin model needs to have a surface barrier that is difficult to puncture like the stratum corneum, and the hardness, elasticity and toughness under the barrier are similar to the real skin to simulate the reaction force after the microneedle penetration. In these aspects, the simulation of a single performance is relatively easy to achieve, but it is not easy to achieve a comprehensive performance similar to the real skin. The application of advanced methods with higher resolution, accurate quantitative and real-time dynamic evaluation of the penetration force and penetration rate of microneedle puncture can help us systematically and accurately analyze microneedle penetration behavior, and the development and application of 3D skin tissue engineering products that are closer to the composition, structure and physical properties of real skin can provide an effective solution path to help establish a more economical and applicable skin model. The establishment of a standardized evaluation model will undoubtedly help advance related research and promote the better industrialization and commercial application of microneedle array technology. In addition, the inherent hardness difference caused by different materials constructed by microneedles, such as metal, monocrystalline silicon and polymer materials, may have a corresponding difference in the penetration rate and penetration depth of real skin or skin model, but this can be solved by providing differentiated judgment methods for different rigid microneedles and formulating different indicators when setting skin model. Therefore, there is no need to design a special skin model to evaluate the puncture behavior of different microneedle.