PDGF‐Releasing Hydrogels for Enhanced Proliferation of Human Nucleus Pulposus Cells

ABSTRACT 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^‐N) 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.