Sulfated Hydrogels in Intervertebral Disc and Cartilage Research.

Emily Lazarus,Iris V Rivero,Iskender Mambetkadyrov,Taylor Schofield,Sloan Howard,Karin Wuertz-Kozak,Mikkael Lamoca,Paola Bermudez-Lekerika,Benjamin Gantenbein,Christopher L Lewis,Daniel Farchione

doi:10.3390/cells10123568

Abstract

Hydrogels are commonly used for the 3D culture of musculoskeletal cells. Sulfated hydrogels, which have seen a growing interest over the past years, provide a microenvironment that help maintain the phenotype of chondrocytes and chondrocyte-like cells and can be used for sustained delivery of growth factors and other drugs. Sulfated hydrogels are hence valuable tools to improve cartilage and intervertebral disc tissue engineering. To further advance the utilization of these hydrogels, we identify and summarize the current knowledge about different sulfated hydrogels, highlight their beneficial effects in cartilage and disc research, and review the biofabrication processes most suitable to secure best quality assurance through deposition fidelity, repeatability, and attainment of biocompatible morphologies.

Highlights

Hydrogels are three-dimensional (3D), chemically or physically crosslinked polymer networks with hydrophilic groups that allow for high water-absorbing capacity
Hydrogels are commonly used as drug delivery systems by providing spatial and temporal control over the release of therapeutics, predominantly via diffusion [2]; the diffusion rate depends on the selected polymer and can be further modified through, e.g., changes in water content, crosslinking density, porosity, and selection of a drug with a suitable diffusion coefficient, diffusion-dominated drug release is typically limited to hours or days
Sulfated hydrogels hold great promise in cartilage and intervertebral disc (IVD) tissue engineering research concerning sustained drug release and phenotypic support, high costs and batch-to-batch variability associated with isolation from tissues are major limitations

Summary

Introduction

Hydrogels are three-dimensional (3D), chemically or physically crosslinked polymer networks with hydrophilic groups that allow for high water-absorbing capacity. Synthetic and natural hydrogels are heavily researched, natural hydrogels such as hyaluronan, heparin, and alginate are commonly favored due to their biocompatibility, biodegradability, non-immunogenicity, and overall resemblance to the extracellular matrix (ECM) of connective tissues Despite their similarity to the IVD and cartilage, these hydrogels lack one crucial feature that originates from the high proteoglycan content of these tissues: the presence of carboxyl and sulfonic acid groups that create the IVD/cartilage-specific negatively charged ECM microenvironment [3]. We focus on demonstrating their suitability as drug delivery systems (Table 1), with sustained release of growth factors and other positively charged drugs due to electrostatic interactions, hydrogen bonding, and other types of interactions [9] We show their suitability to support a chondrogenic cell phenotype commonly lost during in vitro culture (Table 2), which is relevant for research on the chondrocyte-like nucleus pulposus (NP) cells, i.e., the cells from the inner region of the IVD.

Sulfated Hydrogels Used in IVD and Cartilage Research

Biofabrication Techniques

Findings

Conclusions and Outlook