Self-assembling Peptide Hydrogels as a Platform to Mimic the Nucleus Pulposus Microenvironment

Abstract

The intervertebral disc (IVD) is essential for spinal mobility and shock absorption; however, age- and lifestyle-associated degeneration compromises this function and is a major contributor to chronic lower back pain (LBP). The nucleus pulposus (NP) represents the initial site of degeneration, and current clinical treatments are non-curative, motivating the development of regenerative approaches. Mesenchymal stem cells (MSCs) represent a promising autologous cell source for NP regeneration due to their proliferative capacity and differentiation potential. Self-assembling peptide hydrogels (SAPHs) have recently emerged as tunable 3D scaffolds. This study investigated the suitability of SAPHs for NP tissue engineering by examining MSC viability, morphology, and differentiation within hydrogels of varying peptide sequence and pH, using confocal fluorescence microscopy, oscillatory rheology, histology, immunohistochemistry (IHC), and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Hydrogel pH and peptide sequence significantly influenced MSC viability, morphology, and arrangement, while SAPHs supported changes in NP-associated gene expression relative to control conditions. Immunohistochemical and histological analyses revealed qualitative differences in matrix synthesis between hydrogel formulations. A key finding was that SAPHs themselves modulated MSC differentiation. Together, these findings demonstrate that SAPHs provide a supportive and tunable microenvironment for MSC culture and differentiation, supporting their potential as candidate scaffolds for NP tissue engineering and regenerative treatment of intervertebral disc degeneration (IDD).

Date of Award	4 Dec 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Julie Gough (Main Supervisor), Stephen Richardson (Co Supervisor) & Alberto Saiani (Co Supervisor)