Fukunaga Takanori, Pearson Joseph J, Miller Ryan Cree, Zhang Changli, Lakrat Mohammed, Haglund Lisbet, Diaz-Hernandez Martha Elena, Temenoff Johnna S, Drissi Hicham
Musculoskeletal Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
Coulter Department of Biomedical Engineering, Georgia Tech/Emory University, Atlanta, Georgia, USA.
J Biomed Mater Res A. 2025 May;113(5):e37918. doi: 10.1002/jbm.a.37918.
Hydrogels offer a promising solution for sustained and controlled drug delivery and cell-tissue biocompatibility. In the intervertebral disc (IVD), delivering growth factors faces challenges due to the antagonistic inflammatory environment and continuous mechanical stress, which can degrade biological agents and may reduce their local activity. To address this, we investigated the prolonged release of platelet-derived growth factor isoforms BB (PDGF-BB) and AB (PDGF-AB) by using N-desulfated heparin methacrylamide (Hep) crosslinked within matrix-metalloproteinase sensitive poly(ethylene glycol) (PEG) hydrogels. Using electrostatic interactions between the heparin derivative and PDGF, we optimized a sustained release dose of PDGF-BB from the hydrogel in the presence of collagenase to mimic the in vivo environment. We then assessed the effects of PDGF released from PEG-hydrogel on human nucleus pulposus (NP) Cells. The MTT assay confirmed that 100 and 200 ng doses significantly increased cell viability by 2.52-fold and 2.46-fold on Day 3, respectively. RT-qPCR analysis revealed that PDGF-AB and PDGF-BB upregulated the expression of proliferation marker Ki-67 (MKI67) on both Day 3 and Day 5. Additionally, collagen type II alpha 1 chain (COL2A1) was significantly upregulated in the PDGF-AB group on Day 5, indicating potential anabolic effects. These findings could pave the way for long-term in vivo studies on sustainable PDGF treatment for IVD degeneration.
水凝胶为持续和可控的药物递送以及细胞-组织生物相容性提供了一个有前景的解决方案。在椎间盘(IVD)中,由于对抗性的炎症环境和持续的机械应力,递送生长因子面临挑战,这会使生物制剂降解并可能降低其局部活性。为了解决这个问题,我们研究了通过在基质金属蛋白酶敏感的聚(乙二醇)(PEG)水凝胶中交联N-去硫酸化肝素甲基丙烯酰胺(Hep)来实现血小板衍生生长因子亚型BB(PDGF-BB)和AB(PDGF-AB)的长效释放。利用肝素衍生物与PDGF之间的静电相互作用,我们在胶原酶存在的情况下优化了水凝胶中PDGF-BB的持续释放剂量,以模拟体内环境。然后我们评估了从PEG水凝胶释放的PDGF对人髓核(NP)细胞的影响。MTT试验证实,在第3天,100和200 ng剂量分别使细胞活力显著增加了2.52倍和2.46倍。RT-qPCR分析显示,PDGF-AB和PDGF-BB在第3天和第5天都上调了增殖标志物Ki-67(MKI67)的表达。此外,在第5天,PDGF-AB组中II型胶原α1链(COL2A1)显著上调,表明具有潜在的合成代谢作用。这些发现可能为椎间盘退变的可持续PDGF治疗的长期体内研究铺平道路。