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

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Intervertebral disc (IVD) degeneration presents challenges for sustained growth factor delivery due to inflammation and mechanical stress.
• Existing treatments struggle with localized delivery and maintaining the bioactivity of therapeutic agents.

Purpose of the Study:

• To investigate the prolonged release of platelet-derived growth factor isoforms BB (PDGF-BB) and AB (PDGF-AB) using novel hydrogels.
• To assess the impact of released PDGF on human nucleus pulposus (NP) cells for potential IVD degeneration treatment.

Main Methods:

• Developed N-desulfated heparin methacrylamide (Hep^-N) crosslinked within matrix-metalloproteinase sensitive poly(ethylene glycol) (PEG) hydrogels.
• Optimized sustained release of PDGF-BB using electrostatic interactions and collagenase to simulate in vivo conditions.
• Assessed PDGF effects on NP cell viability (MTT assay) and gene expression (RT-qPCR for MKI67 and COL2A1).

Main Results:

• PDGF doses of 100 and 200 ng significantly increased NP cell viability by over 2.4-fold on Day 3.
• Both PDGF-AB and PDGF-BB upregulated the proliferation marker Ki-67 (MKI67) on Days 3 and 5.
• PDGF-AB significantly upregulated collagen type II alpha 1 chain (COL2A1) on Day 5, suggesting anabolic effects.

Conclusions:

• The developed PEG-hydrogel system enables sustained release of PDGF isoforms, enhancing NP cell viability and proliferation.
• The findings indicate potential anabolic effects of PDGF on NP cells, supporting its use for IVD degeneration.
• This study provides a foundation for future in vivo investigations into hydrogel-based PDGF therapy for IVD repair.