Type II collagen-hyaluronan hydrogel – a step towards a scaffold for intervertebral disc tissue engineering

Abstract

Intervertebral disc regeneration strategies based on stem cell differentiation in combination with the design of functional scaffolds is an attractive approach towards repairing/regenerating the nucleus pulposus. The specific aim of this study was to optimise a composite hydrogel composed of type II collagen and hyaluronic acid (HA) as a carrier for mesenchymal stem cells. Hydrogel stabilisation was achieved by means of 1-ethyl-3(3-dimethyl aminopropyl) carbodiimide (EDC) and Nhydroxysuccinimide (NHS) cross-linking. Optimal hydrogel properties were determined by investigating different concentrations of EDC (8mM, 24mM and 48mM). Stable hydrogels were obtained independent of the concentration of carbodiimide used. The hydrogels crosslinked by the lowest concentration of EDC (8mM) demonstrated high swelling properties. Additionally, improved proliferation of seeded rat mesenchymal stem cells (rMSCs) and hydrogel stability levels in culture were observed with this 8mM cross-linked hydrogel. Results from this study indicate that EDC/NHS (8mM) cross-linked type II collagen/HA hydrogel was capable of supporting viability of rMSCs, and furthermore their differentiation into a chondrogenic lineage. Further investigations should be conducted to determine its potential as scaffold for nucleus pulposus regeneration/repair.

A review of the application of reinforced hydrogels and silk as biomaterials for intervertebral disc repair

“…Hence, these are frequently included in possible tissue engineering treatment approaches (Priyadarshani et al, 2015), e.g. agarose (Awad et al, 2004;Bougault et al, 2012;Iwata et al, 2013;Luo et al, 2015;Mauck et al, 2006), collagen (Borde et al, 2015;Calderon et al, 2010;Mercuri et al, 2014;Omlor et al, 2012;Tsaryk et al, 2015), alginate (Bron et al, 2011;Duggal et al, 2009;Xu et al, 2008;Zeng et al, 2015a), chitosan (Naqvi and Buckley, 2015;Ngoenkam et al, 2010), and combinations of alginate and chitosan have been investigated (Shao , 2007). Although natural hydrogels generally offer good cytocompatibility, they often possess inferior mechanical properties (Schutgens et al, 2015).…”

'Cell or Not to Cell' that is the Question: For Intervertebral Disc Regeneration?

“…Traditionally the biocompatability of natural polymer scafolds has been an appealing choice for NP repair, including collagen [121], alginate [65], gelatine [60], hylauronan [67,68], chitosan-glycerophosphate [94,107] and thermoresponsive hyaluronic acid (Table 1) [71]. However the use of natural polymers raises concerns regarding batch variation and immunogenic risk; consequently a number of studies have looked to develop synthetic polymer scafolds which have the added advantage of synthesis control, large scale production and the ability to tailor bioactivity, mechanical properties and degradation rates.…”

Protein-based injectable hydrogels towards the regeneration of articular cartilage

“…The degradation dynamics of Gel/HA hydrogels was studied by enzymatic degradation with a 10 U/ml solution of hyaluronidase and 3 U/mL of collagenase in DPBS, these concentrations being within the range typically used in the bibliography [90], [91], [114], [131], [225], [226]. A mixture of both enzymes was used to study degradation, since it has been demonstrated that the combination of both produces higher degradation rates than when only one is used [69].…”