Stem Cell Delivery with Polymer Hydrogel for Treatment of Intervertebral Disc Degeneration: From 3D Culture to Design of the Delivery Device for Minimally Invasive Therapy

Abstract

Nucleus pulposus (NP) tissue damage can induce detrimental mechanical strain on the biomechanical performance of intervertebral discs (IVDs), causing subsequent disc degeneration. A novel, photocurable, injectable, synthetic polymer hydrogel (pHEMA-co-APMA grafted with PAA) has already demonstrated success in encapsulating and differentiating human mesenchymal stem cells (hMSCs) toward an NP phenotype during hypoxic conditions. After demonstration of promising results in our previous work, in this study we have further investigated the inclusion of mechanical stimulation and its impact on hMSC differentiation toward an NP phenotype through the characterization of matrix markers such as SOX-9, aggrecan, and collagen II. Furthermore, investigations were undertaken in order to approximate delivery parameters for an injection delivery device, which could be used to transport hMSCs suspended in hydrogel into the IVD. hMSC-laden hydrogel solutions were injected through various needle gauge sizes in order to determine its impact on postinjection cell viability and IVD tissue penetration. Interpretation of these data informed the design of a potential minimally invasive injection device, which could successfully inject hMSCs encapsulated in a UV-curable polymer into NP, prior to photo-cross-linking in situ.