随着基因工程和生物制药工程的蓬勃发展，治疗性蛋白/多肽被广泛应用于传染病、遗传病、癌症和许多其他疾病的临床治疗中。由于大多数蛋白制剂存着生物半衰期短、给药频率高、患者依从性差等问题，严重限制了其治疗效果。因此，开发可长效控释活性大分子的递送系统对蛋白制剂的临床应用是一项迫切且巨大的挑战。针对上述问题，本文采用可维持药物活性和具有长效控释功能的亲和力递送策略，致力于蛋白药物递送系统的设计开发，构建了亲和控释系统的可预测数学模型，并指导开发面向生理条件下带电的水溶性蛋白的新型聚离子水凝胶控释体系，结合3D打印技术构建载药组织工程支架并探索其在个性化治疗中的应用。论文取得的主要研究成果有：1）针对基于亲和力原理控释药物的水凝胶递送体系，依据三种基础拓扑结构单元构建了药物递送数学模型，用于预测该递送系统中的药物释放动力学以及指导设计后续的亲和控释药物递送体系；2）针对水溶性蛋白，设计开发了兼具药物控释性能、良好细胞相容性、仿生理化性能的聚阴离子水凝胶体系和聚阳离子水凝胶材料体系，通过控制亲和配体浓度分别实现了正电性蛋白溶菌酶以及负电性蛋白酸酐化牛β-乳球蛋白在不同量级时长（小时、天或月）的可控释放；3）基于聚阴离子水凝胶体系，借助3D打印技术设计制备了具有仿生皮肤性能、良好细胞相容性、bFGF亲和控释功能的载药皮肤补片，大鼠全层皮肤缺损模型植入结果表明该载药支架可促进创口的修复愈合；4）开发了兼具良好弹性和药物可控递送性能的聚阳离子双网络水凝胶材料体系，并使用3D打印技术构建了个性化的仿生宫颈修复体，基于亲和力递送策略可搭载控释负电性抗HPV蛋白，为宫颈锥切术后的组织修复以及HPV病毒防治提供了新的治疗策略。综上，为了解决蛋白/多肽类药物无法长期可控有效递送的问题，本研究开发了基于亲和力控释蛋白的聚离子水凝胶体系，重点从数学模型构建、聚离子水凝胶材料开发以及组织工程领域的具体应用等方面展开了系统研究，解决了亲和力控释系统的理论模型构建问题，为亲和力控释递送系统的开发设计提供了新工具和新材料，也为个性化载药组织补片的构建提供了新策略和新思路。

With the vigorous development of genetic engineering and biopharmaceutical engineering, therapeutic proteins/peptides have been widely used in the clinical treatment of infectious diseases, genetic diseases, cancer and many other diseases. Due to the short biological half-life, high administration frequency and poor patient compliance, most protein drugs preserve severely limited therapeutic effects. Therefore, development of a delivery system with long-term controlled release function for active macromolecules is an urgent and huge challenge for the clinical application of therapeutic proteins/peptides.In this study, we proposed a polyionic hydrogel protein drug delivery system with adapting the affinity-based delivery strategy, which could maintain drug activity and has a long-term controlled release function. A predictable mathematical model for the affinity-controlled release system was constructed, which was used to guide the development of polyion hydrogel controlled release system for charged water-soluble proteins. With the help of 3D printing technology, drug-loaded tissue engineering scaffolds were constructed and applied in personalized therapy. The main research achievements of this thesis are as follows: 1) A predictable mathematical model was constructed, which can be used to predict the drug release kinetics and guide the design of affinity-controlled drug delivery system; 2) For water-soluble proteins, polyanion hydrogel system and polycationic hydrogel material system with drug controlled-release performance, good cell compatibility and physiomimetic performance were developed. The controlled release of positively charged protein lysozyme and negatively charged protein anhydride bovine lactoglobulin in different time scales was achieved by controlling the concentration of affinity ligand; 3) Based on the polyanion hydrogel system, a drug-loaded bionic skin patch with good biocompatibility and bFGF affinity controlled-release function was designed and prepared by 3D printing technology. After implantation into the rat with full-thickness skin defect, the bFGF-loaded skin patch was found to promote the repair and healing of the wound; 4) A polycationic double network hydrogel material system was synthetised to controllably release the negatively charged anti-HPV protein towards cervical cancer treatment. Thanks to the good elasticity of the hydrigel, a personalized bionic cervix was constructed using 3D printing technology. Based on the affinity-guided delivery strategy, the fabricated cervix model provides a novel strategy for tissue repair and HPV virus prevention after cervical conization.In conclusion, this study developed a polyionic hydrogel protein delivery system with affinity-controlled release fucntionality, focusing on the construction of predictable mathematical models, the development of polyionic hydrogel materials, and the specific applications in the field of tissue engineering. It solves the problem of theoretical model construction of affinity-controlled release system, provides new tools and material choice for protein delivery system, as well as the new strategies for the construction of personalized drug-loaded tissue scaffolds.