Date of Award

12-2015

Document Type

Thesis

Degree Name

Master of Engineering (ME)

Legacy Department

Bioengineering

Advisor

Mercuri, Jeremy

Committee Member

Simionescu, Dan

Committee Member

Gill, Sanjitpal

Abstract

Annually, over 5.7 million Americans are diagnosed with two IVD-associated pathologies: IVD herniation (IVDH- a mechanical disruption of the concentric fibrous layers of the annulus fibrosus (AF))) and degeneration (IVDD- a multifactorial process which initiates within the inner gelatinous core (NP), and results in a biochemical degradation of NP tissue), with over 2.7 million requiring surgical inteventions.1,2 Although both underlying pathologies are different, quite often they both lead to a decrease in IVD height, impaired mechanical function, and increased pain and disability. These pain symptoms affect approximately 80% of the adult population during their lifetime with estimated expenditures exceeding $85.9 billion.3,4 Current surgical procedures for IVDH and IVDD are palliative and suffer from drawbacks. While they are performed to address patient symptoms, they fail to address the underlying pathology of a defect remaining within the subsequent layers of the AF. An effective AF closure/repair device in conjunction with a less aggressive discectomy for IVDH and/or NP arthroplasty for IVDD, may result in improved patient outcomes, decreased pain, and provide fewer revision surgeries via lower re-herniation and expulsion rates.5,6 Therefore, an intact AF must be re-established to prevent implant expulsion or re-herniation, thus addressing the two major spinal pathologies directly associated with an IVD. Currently within the medical device market, no tissue engineering biomaterials are available for AF closure/repair. Current market AF closure devices (Intrinsic Barricaid, Anulex X-Close Tissue Repair System, and Anulex Inclose Surgical Mesh System) are synthetic materials focused solely on preserving and reinforcing the native tissue and lack efficient strategies for implantation, fixation, and regeneration. Therefore, there has been an increase in tissue engineering and regenerative therapeutic approaches aiming for structural and biological AF repair investigated over the last decade using in vivo and in vitro experimentation. It is proposed that the optimum AF tissue engineering scaffold should reproduce the architecture, and the mechanical properties of the native human AF tissue.7 Recent articles illustrate several novel suture, seal, and barrier techniques currently under development, resulting in an increasing attention at scientific workshops and conferences.8-15 To develop a tissue engineering biomaterial that is suitable for AF closure it must meet the following criteria: (1) mimic the structural angle-ply architecture of the native AF, (2) withstand static and dynamic mechanical properties mimicking the native functional characteristics, and (3) express cytocompatibility while promoting tissue regeneration. Current biomaterials growing attention in the tissue engineering academic field, electrospinning, polymers, glue, silk scaffolds, and honeycomb-scaffolds, require complex manufacturing procedures and typically work to address two of the three criteria (mimicking the biological and structural characteristics).5 Although the mechanical advantage of closing annular defects to retain NP material seems intuitive, only recently have AF closure devices begun to examined in human cadaveric or animal tissues for their ability to withstand in situ IDP or flexibility testing.16 Therefore, the use of decellularized tissue from a xenogeneic source is ideal due to its advantage of maintaining native extracellular matrix (ECM) while also removing all potential harmful xenogeneic factors. We propose to address all three criteria with the development of a biomimetic angle-ply annulus fibrosus patch comprised of decellularized porcine pericardium. Porcine pericardium was chosen due to its native type I collagen content, mechanical strength, and cytocompatibility. The objectives of this research were to investigate the development of a biomimetic patch, consisting of decellularized porcine pericardium, to biologically augment AF repair by (1) characterizing the micro-architecture of the multi-laminate angle-ply AF patch, (2) evaluating the mechanical properties through static and dynamic tensile loading and impact resistance of IDP, and (3) evaluating the cytocompatibility of the patch using a healthy alternative cell source for AF tissue regeneration.

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Engineering Commons

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