Lower Macromer Concentration Enhances Nucleus Pulposus-Like Differentiation and Functional Extracellular Matrix Assembly by Human Marrow-Derived Stromal Cells Encapsulated in Photocrosslinked Carboxymethylcellulose Hydrogels

Abstract

Intervertebral disc (IVD) degeneration is associated with dehydration and loss of integrity of the nucleus pulposus (NP) region of the disc. The NP is a tissue comprised mainly of proteoglycans and type II collagen (COL II) [1]. Tissue engineering therapies could provide viable NP replacements as an alternative to current surgical procedures. Recently, photocrosslinked carboxymethylcellulose (CMC) hydrogels were shown to support cell viability and the assembly of functional extracellular matrix (ECM) by encapsulated human marrow-derived mesenchymal stromal cells (hMSCs) when cultured in serum-free, chemically defined medium with TGF-β3 [2]. Previous studies have shown that scaffold macromer density can influence functional mechanical properties and chondrogenic differentiation of several cells types in various hydrogel systems [3,4,5]. However, the impact of macromer concentration on hMSC differentiation in CMC hydrogels has not been evaluated. Therefore, the objective of this study was to examine the effects of CMC macromer concentration on NP-like differentiation and the elaboration of functional ECM in hMSC-laden CMC constructs.