Mechanism and Application Status of PRP-loaded Hydrogels in the Treatment of KOA
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摘要: 膝骨关节炎（knee osteoarthritis，KOA）是一种常见于中老年的慢性退行性骨关节病，主要特征是膝关节软骨退化和磨损，严重影响下肢活动和生活质量。目前，对于早、中期KOA的治疗主要依赖口服药物、关节注射、外用贴剂和中医药方法等保守方法。富血小板血浆（platelet-rich plasma，PRP）作为一种自体来源的血小板浓缩物，富含多种生长因子且无免疫排斥风险，近年来在骨关节和软组织损伤的修复中得到广泛应用。然而，PRP中生长因子的生物半衰期较短和注射部位的流动性，在关节腔内存在结合力不足、作用时间短、靶位治疗效果差、需要重复注射等问题，也增加了医源性感染的风险。水凝胶是含水的交联聚合物网络，其高组织相容性和药物缓释性备受关注。将PRP负载于水凝胶实现了药物的缓慢、持续释放，其独特的黏附性降低了药物在关节内的流动，从而延长了PRP局部作用时间，减少了重复注射的需求。本文通过综述PRP、水凝胶的生物学特性及负载PRP的水凝胶治疗KOA的作用机制、临床应用现状，并分析了存在的问题及面临的挑战，旨在通过对这一新兴治疗方法的深入探讨，为KOA患者提供更为有效的治疗选择。Abstract: Knee osteoarthritis （KOA） is a common chronic degenerative bone and joint disease characterized by degeneration and wear of knee cartilage. It is commonly found in middle-aged and elderly people and seriously impacts on their lower limb activity and quality of life. At present, the treatment of early and middle stage KOA mainly relies on the conservative methods such as oral medication, joint injection, topical patches and traditional Chinese medicine. Platelet rich plasma （PRP）, as an autologous platelet concentrate, is rich in various growth factors and has no risk of immune rejection. In recent years, it has been widely used in the repair of bone, joint, and soft tissue injuries. However, the short biological half-life of growth factors in PRP and the fluidity of injection sites can result in insufficient binding force, short action time, poor target therapy efficacy, and the need for repeated injections in the joint cavity, which will increase the risk of iatrogenic infections. Hydrogels are cross-linked polymer networks containing water, and their high histocompatibility and drug release have attracted much attention. The slow and continuous release of drug is achieved by loading PRP onto hydrogel. Its unique adhesion reduces the flow of drug in the joint, thus extending the local action time of PRP and reducing the need for repeated injection. This article reviews the biological characteristics of PRP and hydrogel, the mechanism of action and clinical application of PRP loaded hydrogel in the treatment of KOA, and analyzes the existing problems and challenges, aiming to provide more effective treatment options for KOA patients through the in-depth discussion of this new treatment method.
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Key words:
- Knee osteoarthritis /
- Platelet-rich plasma /
- Hydrogel /
- Mechanisms /
- Applications
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图 1 负载PRP的水凝胶缓释生长因子协同促进软骨再生的可能的分子通路
Figure 1. Possible molecular pathways of PRP loaded hydrogel sustained-release growth factor synergistically promoting cartilage regeneration
图 3 PRP通过TGF-β/SMAD信号通路促进MSC-胶原水凝胶软骨再生的可能机制
Figure 3. The possible mechanism of PRP promoting MSc-collagen hydrogel cartilage regeneration through TGF-β/SMAD signaling pathway
图 4 PRP通过TGF-β/SMAD信号通路促进MSC-胶原水凝胶软骨再生的可能机制
Figure 4. The possible mechanism of PRP promoting cartilage regeneration of MSC-collagen hydrogel through TGF-β/SMAD signaling pathway
图 5 PRP-GelMA水凝胶促进骨软骨缺损修复的可能机制
Figure 5. The possible mechanism of PRP-GelMA hydrogel in promoting the repair of osteochondral defects
图 6 PRP/m-HA复合支架缓释生长因子促进模型猪股骨髁软骨再生的动物实验设计
A：自体PRP制备示意图；B：m-HA水凝胶的扫描电镜；C：实验程序示意图；D：股骨内侧髁浅层软骨缺损（FT）和全层骨软骨缺损（底部）。
Figure 6. Animal experimental design of PRP/m-HA composite scaffold slow-release growth factor promoting the regeneration of femoral condylar cartilage in model pigs
表 1 用于软骨组织工程的天然和合成水凝胶生物特性和理化性质及其优缺点
Table 1. Biological and physicochemical properties，advantages and disadvantages of natural and synthetic hydrogels for cartilage tissue engineering
材料 优点 缺点 透明质酸 良好的生物相容性和生物降解性，
润滑性能、水溶性、低免疫原性机械强度差，保留时间短，细胞黏附性差 明胶 由于具有RGD序列而促进细胞黏附 凝胶化时间长，热稳定性差 聚乙二醇 良好的机械性能，易于改性 生物惰性 壳聚糖 良好的生物相容性和生物降解性，
抗菌特性、促进细胞增殖机械强度差，水溶性差 海藻酸盐 良好的孔隙率和生物相容性，成胶迅速 机械强度差，缺乏细胞锚定位点，
细胞黏附性差，生物降解性差硫酸软骨素 软骨细胞外基质的主要成分，抗炎特性，
可维持干细胞生态位，调节酶活性机械强度差，降解迅速 胶原蛋白 良好的生物相容性和生物降解性 机械强度差 丝素蛋白 结构与胶原蛋白相似，机械强度高，
生物相容性，促进细胞黏附生物降解性差 聚N-异丙基丙烯酰胶 热敏性 生物降解性差，机械强度差 聚乙烯醇 良好的生物相容性和机械性能，压缩模量、
剪切模量、拉伸模量和渗透性更接近软骨细胞黏附性差、不可降解 聚丙烯酰胺 三维多孔结构，良好的生物相容性 机械强度差，细胞相互作用不良 
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