Implementation of a Hydrogel-Based IVD Device

Looking towards the implementation of a PVA hydrogel IVD device, the end- plates must be designed for fixation to the adjacent vertebral bodies either mechanically or through tissue ingrowth. Since wear in PVA hydrogels may not be desirable due to hydrogel surface damage and generation of wear debris over time, designs that result in motion between the hydrogel material and a component used for implant fixation could be avoided. Metals such as cobalt chromium and titanium alloys are typically used in orthopedic and spinal implants, and participate in mechanical and/or bony fixation of an

implant. However, it could be a challenge to integrate the hydrogel with a metal compo- nent in the implant without relative motion between the two components.

Our mould design accommodates the addition of endplates to the two-component hydrogel structure. PVA-based endplates could be fabricated separately from the annu- lus-nucleus construct then adhered to the construct using a PVA solution and F-T cycling. Depending on endplate design, platens used in compression testing of a PVA hydrogel- based IVD could be solid or porous. Solid platens should be used for a solid endplate design, while porous platens should be used if the hydrogel is to be attached through po- rous endplates or directly to the vertebral bodies. Allowing fluid flow from the ends of the hydrogel disc would decrease pressurization, and likely decrease stiffness, affect strain rate dependence, and increase stress relaxation and creep. In vitro testing, includ- ing mechanical testing, of a multi-component PVA hydrogel IVD replacement should reflect the implementation and in vivo environment of the device in its application in the cervical IVD.

Freeze-thaw PVA hydrogels have also been studied extensively as controlled drug delivery devices, including applications in treatment of respiratory, skin and cardiovascu- lar diseases [10, 26, 118, 254-262]. Therapeutic agents, such as antibiotics to prevent infection, anti-inflammatory agents to mitigate heterotopic ossification [98], or growth factors to encourage bone or cartilage growth, may be incorporated into a PVA hydrogel device to achieve sustained localized release. The mechanism and rate of release depends on factors including, but not limited to, the concentration and solubility of the drug, hy- drogel concentration, number of FTCs, and the structure of the hydrogel device. For ex- ample, a reservoir-type system could achieve zero-order release, the rate of which does not change with time. Kennedy demonstrated this in a bilayer 10% PVA hydrogel struc- ture composed of a 3 FTC membrane and 1 FTC reservoir [262]. A multi-component PVA hydrogel-based IVD would be well suited as a reservoir-type drug delivery system since the drug could be loaded into the lower polymer concentration nucleus, while the higher concentration annulus would control the rate of release. In a matrix-type system, where the drug is distributed uniformly in the hydrogel, the rate of release decreases with

time. This would be useful if therapeutic activity is required for a period of time imme- diately after implantation. Depending on the desired timing and location of release, therapeutic agents may be placed selectively within the different components of the PVA hydrogel IVD to tailor the release profile, location, and bioactivity.

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A two-component PVA hydrogel structure was successfully produced by F-T cy- cling, consisting of annulus and nucleus components of two different PVA concentra- tions, 20% and 10% PVA, respectively. Unconfined compression to 0.25 strain at strain rates between 0.001%/s and 100%/s were performed. In contrast to the single component 10% and 20% hydrogels, a small toe region of 0.02 strain was observed in the J-shaped stress-strain curves. The two-component hydrogel was expected to have stiffness and viscoelastic response between those of 10% and 20% PVA. However, it was stiffer than the model prediction based on the cross-sectional area of the components and the stress- strain curves of 10% and 20% PVA hydrogels, as well as the single component 20% PVA hydrogel, despite the presence of the more compliant 10% PVA nucleus. The degree of strain rate dependence was between those of single component 10% and 20% PVA hy- drogels, but was closer to the more strain rate dependent 10% PVA, even though the 20% PVA annulus comprised 85% of the construct. Meanwhile, the hydrogel prototype ex- perienced less stress relaxation and had higher creep resistance compared to both the 10% and 20% PVA hydrogels.

This two-component PVA hydrogel prototype demonstrated that a hydrogel struc- ture with multiple components could be produced. However, it was not of sufficient stiffness to be used as a cervical IVD replacement with its current composition. Stiffness, strain rate dependence, stress relaxation and creep must be optimized for applications in the cervical spine. PVA hydrogels possess a great deal of versatility towards producing a functional multi-component cervical IVD prosthesis. Parameters that could be varied to modify PVA hydrogel properties include polymer concentration, the ratio of annulus to

nucleus volume, nanofiller placement and alignment, and straining of the hydrogel during F-T cycling to induce anisotropy. The addition of endplates could also affect compres- sion properties by modulating fluid flow. Creep recovery and resistance to fatigue should also be evaluated for its suitability in the cervical spine. Further considerations in the de- sign of a PVA-based hydrogel TDR could include drug delivery and fixation of the de- vice to adjacent vertebral bodies.

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