目的: 本研究旨在明确富血小板血浆（platelet-rich plasma,PRP）中生长因子[转化生长因子（transforming growth factor-β,TGF-β）、血小板源性生长因子（platelet derived growth factor,PDGF）、胰岛素样生长因子（insulin-likes growth factor,IGF）]浓度对半月板损伤修复的剂量效应关系。方法: 纳入2021—2024年80例急性半月板损伤患者,其中60例按上述三种生长因子综合Z评分分为低、中、高生物活性组（n=20/组）,另20例为生理盐水对照组。采用单一供体制备标准PRP（基础浓度：TGF-β 18.5 ng/mL）,通过添加冻干人重组生长因子（TGF-β：HumanZyme HZ-1023）梯度校正至目标浓度窗（低组12~15 ng/mL;中组18~22 ng/mL;高组25~30 ng/mL）,各批次复溶后实测浓度偏差<5%,干预前后采用MRI改良Stoller评分及Lysholm/IKDC功能量表评估疗效。结果: 高生物活性组修复评分显著优于对照组[（24.5±2.3） vs （17.9±2.5）,P<0.001）];综合评分与功能改善呈强正相关（r=0.79,P<0.001）,且TGF-β贡献度最高（回归β=0.62,95%CI：0.48~0.76）;ROC曲线确定综合评分>1.2（AUC=0.88）为最佳治疗阈值,对应生长因子有效浓度窗为TGF-β 23.5~28.7 ng/mL、PDGF 17.2~20.4 ng/mL、IGF 11.3~14.1 ng/mL。结论: PRP修复效能呈浓度依赖性,基于综合评分的冻干PRP精准调控可优化疗效,当TGF-β浓度>23.5 ng/mL时修复效能显著提升。
Abstract
Objective This study aims to clarify the dose-response relationship between the concentrations of growth factors (TGF-β, PDGF, IGF) in platelet-rich plasma (PRP) and the repair of meniscus injury. Methods 80 patients with acute meniscal injury were enrolled from 2021 to 2024. Among them, 60 patients were divided into low-, medium-, and high-bioactivity groups based on the composite Z-score of three growth factors (TGF-β, PDGF, IGF) (n=20 per group), while the remaining 20 patients served as the saline control group. Standard PRP prepared from a single donor was used (baseline concentration: TGF-β 18.5 ng/mL). The target concentration windows were achieved by gradient-adjusting with lyophilized human recombinant growth factor (TGF-β: HumanZyme HZ-1023) (low group: 12-15 ng/mL; medium group: 18-22 ng/mL; high group: 25-30 ng/mL). Measured concentration deviation after reconstitution was<5% for all batches. Efficacy was evaluated using the modified MRI Stoller score and Lysholm/IKDC functional scales pre- and post-intervention. Results The repair score of the high biological activity group was significantly better than that of the control group (24.5±2.3 vs 17.9±2.5, P<0.001); The comprehensive score was strongly positively correlated with functional improvement (r=0.79, P<0.001), and TGF-β had the highest contribution (regression β=0.62, 95% CI: 0.48-0.76); The ROC curve determines that a comprehensive score>1.2 (AUC=0.88) is the optimal treatment threshold, corresponding to an effective concentration window of growth factors TGF-β 23.5-28.7 ng/mL、PDGF 17.2-20.4 ng/mL、IGF 11.3-14.1 ng/mL. Conclusion The repair efficacy of PRP is concentration dependent, and precise regulation of freeze-dried PRP based on comprehensive scoring can optimize the therapeutic effect. When the concentration of TGF-β is greater than 23.5 ng/mL, the repair efficacy is significantly improved.
关键词
富血小板血浆 /
生长因子浓度 /
半月板修复 /
个性化治疗
Key words
platelet-rich plasma /
growth factor concentration /
meniscal repair /
personalized treatment
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 刘鹏鹏, 谢子康. 半月板损伤修复术的研究进展[J]. 中国矫形外科杂志, 2024, 32(06): 535-540.
[2] 万新雨, 胡震, 杨阳, 等. 富血小板血浆促进半月板修复的研究进展[J]. 中国矫形外科杂志. 2024, 32(08): 727-732.
[3] BOSWELL SG, COLE BJ, SUNDMAN EA, et al.Platelet-rich plasma: a milieu of bioactive factors[J]. Arthroscopy, 2012, 28(3): 429-439.
[4] BARASTEGUI D, ALENTORN-GELI E, GOTECHA D, et al.Treatment of Partial Posterior Cruciate Ligament Injuries with Platelet-Rich Plasma in Growth Factors (PRGF) Intraligamentous Infiltration and a Specific Knee Brace[J]. Surg J (NY), 2021, 7(1): e30-e34.
[5] 游茗柯, 罗俊容, 付维力, 等. 生长因子在半月板修复中的应用研究进展[J]. 中国运动医学杂志. 2020, 39(12): 988-994.
[6] 樊红星, 孟祥虹, 刘晓鸣, 等. 基于MRI影像组学诊断半月板损伤分级的可行性研究[J]. 临床放射学杂志. 2024, 43(05): 798-805.
[7] 杨丽娟, 胡燕, 吴雅娟, 等. 富血小板血浆采集制备及质量控制的回顾性分析[J].2023, 36(10): 946-948.
[8] 杨庆磊, 喻红英, 刘慧敏. 超声引导下 PRP 关节腔内精准注射辅助全内重建术在后交叉韧带损伤中的应用研究[J]. 中国实用医药2024, 19(10): 25-29.
[9] 严斌, 刘刚, 张林, 等. 自体PRP注射联合依托考昔治疗膝关节骨性关节炎效果及对细胞因子的影响[J]. 河北医科大学学报, 2023, 44(1): 57-61.
[10] 李海军, 胡友珍, 冯世波. 核磁共振在评价超短波治疗对于膝关节损伤模型关节功能恢复中的价值[J]. 临床和实验医学杂志, 2021, 20(10): 1058-1061.
[11] YANG Q, ZHANG R, ZHAO L.TGF-β1 Activates Smad2/3 to Enhance Type II Collagen Synthesis and Suppress MMP-13 in Meniscal Fibrochondrocytes[J]. J Orthop Res, 2021, 39(5): 1099-1108.
[12] CHEN X, LIU Y, SUN J.Suboptimal TGF-β Concentration Induces Incomplete Fibrocartilage Repair via Smad Pathway Suppression[J]. Am J Sports Med, 2022, 50(7): 1890-1898.
[13] ZHANG H, WANG F, JIANG Y.PDGF/IGF Synergistically Promotes Angiogenesis and Anti-Inflammatory Response in Meniscal Regeneration via PI3K/Akt-NF-κB Axis[J]. Biomater Sci, 2020, 8(24): 6932-6944.
[14] LI S, TANG C, GAO Y.Excessive TGF-β1 Disrupts Collagen Fiber Alignment by Antagonizing PDGF/IGF Signaling in Meniscal Repair[J]. Cell Tissue Res, 2019, 378(2): 287-299.
[15] KON E, DI MATTEO B, FILARDO G.Platelet-Rich Plasma for Degenerative Meniscus Tears: A Randomized Controlled Trial with Concentration-Response Analysis[J]. Arthroscopy, 2021, 37(5): 1485-1492.
[16] XU J, LIAO Z, WU Z.Inter-Batch Variability in Growth Factor Concentrations of Liquid PRP: Implications for Clinical Efficacy[J]. Platelets, 2023, 34(1): 88-95.
[17] WANG L, WEI K, ZHANG B.TNF-α Downregulates TGF-β Receptor Expression and Impairs Repair in Chronic Meniscal Injury[J]. Osteoarthritis Cartilage, 2022, 30(8): 1123-1134.
[18] ZHAO M, LIU X, CHEN S.Elevated TGF-β Threshold for Effective Repair in Chronic Meniscal Tears: A Prospective Cohort Study[J]. J Orthop Transl, 2020, 24: 188-196.
基金
四川省卫生健康委员会科技项目“从免疫细胞群 Cross-Talk 研究机械压力平衡炎性微环境加速骨骼肌修复的调控机制”（24WSXT002）
PDF(1904 KB)
