Angle-ply biomaterial scaffold for annulus fibrosus repair replicates native tissue mechanical properties, restores spinal kinematics, and supports cell viability

Abstract

Annulus fibrosus (AF) damage commonly occurs due to intervertebral disc (IVD) degeneration/herniation. The dynamic mechanical role of the AF is essential for proper IVD function and thus it is imperative that biomaterials developed to repair the AF withstand the mechanical rigors of the native tissue. Furthermore, these biomaterials must resist accelerated degradation within the proteolytic environment of degenerate IVDs while supporting integration with host tissue. We have previously reported a novel approach for developing collagen-based, multi-laminate AF repair patches (AFRPs) that mimic the angle-ply architecture and basic tensile properties of the human AF. Herein, we further evaluate AFRPs for their: tensile fatigue and impact burst strength, IVD attachment strength, and contribution to functional spinal unit (FSU) kinematics following IVD repair. Additionally, AFRP resistance to collagenase degradation and cytocompatibility were assessed following chemical crosslinking. In summary, AFRPs demonstrated enhanced durability at high applied stress amplitudes compared to human AF and withstood radially-directed biaxial stresses commonly borne by the native tissue prior to failure/detachment from IVDs. Moreover, FSUs repaired with AFRPs and nucleus pulposus (NP) surrogates had their axial kinematic parameters restored to intact levels. Finally, carbodiimide crosslinked AFRPs resisted accelerated collagenase digestion without detrimentally effecting AFRP tensile properties or cytocompatibility. Taken together, AFRPs demonstrate the mechanical robustness and enzymatic stability required for implantation into the damaged/degenerate IVD while supporting AF cell infiltration and viability.

Ethanol‐mediated compaction and cross‐linking enhance mechanical properties and degradation resistance while maintaining cytocompatibility of a nucleus pulposus scaffold

“…We have previously demonstrated that bovine caudal NPs can be effectively decellularized to produce human‐mimetic NP scaffolds with similar ECM composition, mechanical properties, and cytocompatibility; however, the mechanical testing values were lower than those reported for human NP . This was in agreement with our bovine explant FSU model, for which the ABNP was not able to restore the viscoelastic creep parameters following repair . These mechanical deficiencies were attributed to decellularization‐induced changes that increased ECM porosity and permeability due to free‐swelling, GAG leaching, and tissue damage, which has been observed in other decellularization methodologies for NP tissue …”

“…Bovine caudal NPs have shown biochemical and microarchitectural similarities to human NP . We have previously described an acellular bovine NP (ABNP) which possessed biomimetic ECM composition and supported cell seeding, and have recently shown its ability to partially restore spine kinematics using a bovine explant functional spinal unit model when used in tandem with an AF repair patch . There remains a need to optimize the ABNP prior to its implementation as a therapeutic for IDD to ensure it is mechanically competent when confronted with enzymatic degradation.…”

Decellularization and characterization of a whole intervertebral disk xenograft scaffold

“…The former observation was likely due in part to ultrasonication which has been shown to be an effective method for decellularizing dense fibrous tissues by loosening fiber networks. 21 However, recent studies by our group have demonstrated that this loosening can be beneficial for supporting increased cell infiltration without significantly impacting tensile strength of multi-laminate angle-ply biomaterials. 21 Moreover, the overall angle-ply lamellar architecture, collagen fiber network and alignment of the native outer AF was retained in the decellularized whole bovine IVDs.…”

“…Our group has previously reported on the development of top-down approach for creating acellular scaffolds for IVD repair and regeneration. [21][22][23] More specifically, a decellularization process was developed to create an acellular scaffold from excised bovine tail (coccygeal; CC) IVD NP tissue while concomitantly retaining the primary biochemical composition and ECM microarchitecture of the native tissue. 22 Bovine tail IVDs were chosen as a starting material for scaffold development because they have been shown to have similar biochemical composition, structural organization, resting stress and height to diameter ratio when compared to human lumbar IVDs.…”

Multi-laminate Annulus Fibrosus Repair Scaffold with an Interlamellar Matrix Enhances Impact Resistance, Prevents Herniation and Assists in Restoring Spinal Kinematics

“…(McGuire et al, 2016) Additionally, the AFRPs mechanical properties have been previously characterized demonstrating similarity to human AF; however, its ability to withstand high-impact loading warranted enhancement. (Borem et al, 2017) The AF's ability to resist radially-directed impact is thought to be supported in part by the energy dissipative function of GAG found within the ILM. Perie et al, 2006) Thus, we hypothesized the impact resistance of the AFRP would be increased via the inclusion of a GAG-based hydrogel ILM.…”