Material properties in unconfined compression of human nucleus pulposus, injectable hyaluronic acid-based hydrogels and tissue engineering scaffolds

Abstract

Surgical treatment for lower back pain related to degenerative disc disease commonly includes discectomy and spinal fusion. While surgical intervention may provide short-term pain relief, it results in altered biomechanics of the spine and may lead to further degenerative changes in adjacent segments. One non-fusion technique currently being investigated is nucleus pulposus (NP) support via either an injectable hydrogel or tissue engineered construct. A major challenge for either approach is to mimic the mechanical properties of native NP. Here we adopt an unconfined compression testing configuration to assess toe-region and linear-region modulus and Poisson's ratio, key functional parameters for NP replacement. Human NP, experimental biocompatible hydrogel formulations composed of hyaluronic acid (HA), PEG-g-chitosan, and gelatin, and conventional alginate and agarose gels were investigated as injectable NP replacements or tissue engineering scaffolds. Testing consisted of a stress-relaxation experiment of 5% strain increments followed by 5-min relaxation periods to a total of 25% strain. Human NP had an average linear-region modulus of 5.39 +/- 2.56 kPa and a Poisson's ratio of 0.62 +/- 0.15. The modulus and Poisson's ratio are important parameters for evaluating the design of implant materials and scaffolds. The synthetic HA-based hydrogels approximated NP well and may serve as suitable NP implant materials.

Scaffolding in tissue engineering: general approaches and tissue-specific considerations

“…Further enhancement in the swelling and mechanical stability of the scaffolds for nucleus or annulus replacement such as crosslinking without compromising cell viability [45] should be encouraged as these physical properties favor the restoration and maintenance of disc height. Evaluation of the mechanical properties of injectable polymers such as hyaluronic acid gel [28] and polyethylene glycol [115] against different engineering parameters should also be encouraged as replacing the mechanical function is equally important as replacing the cellular function in matrix secretion in this stage of degeneration.…”

Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering

“…The addition of a biomaterial carrier has the potential to increase cell viability and enable long-term growth factor delivery. Various synthetic and natural materials are currently being investigated for nucleus pulposus tissue engineering [21][22][23][24][25][26]. However, synthetic materials, such as chemically modified hyaluronan, can have toxic byproducts or result in a foreign body response [27][28][29].…”

Mechanical response of 3D Insert® PCL to compression

“…In order to obtain reproducibility of the response to compression, pre-stresses existing in the scaffolds must be prevented. For this purpose, static pre-conditioning was proposed in multiple studies [18]- [20] as a method to prevent progressive relaxation of the structure undergoing dynamic cycles. Environmental conditions are known to affect the mechanical response of scaffolds [21] as demonstrated by Dynamic Mechanical Analysis (DMA) in previous literature studies [14], [15], [17].…”