A new spine interbody fusion system: Integrating topology optimized biodegradable interbody fusion cages with cell-based and ex vivo gene therapy.

摘要

Spine injuries and pathologies including disc degeneration, stenosis, spondylolysis, and/or spondylolisthesis represent more than one-half of the musculoskeletal impairments reported in the United States. While interbody fusion relieves pain by eliminating spinal instability, complications associated with conventional metallic cage, including implant migration or failure, imaging artifact and stress shielding, and limited bone grafting significantly reduce the efficacy of the interbody fusion. In this work, a novel interbody fusion system is proposed as an alternative by integrating the design principle of topology optimization, the controlled load transfer by an osteoconductive biodegradable polymer composite, and cell-based and gene therapy.; The integrated local-global topology optimization method developed in this thesis creates a cage design that addresses limitations of conventional cage designs by providing optimal distribution of material under applied force to satisfy the objective of maximal stiffness with desired porosity, under constraints of design criteria, concurrently enhancing stability, and providing sufficient porosity for biofactor delivery and mechanical tissue stimulation. More limited displacement with the range of 0.005 to 0.007 mm reduces the incidence of early retropulsion along anterior-posterior (AP) axis compared to the threaded design with 0 to 0.1 mm in the AP direction and the controlled strain less than 8% provides favorable stimulation for appositional bone formation at the bone implant interface. Lower contact stress on vertebrae reduces the risk of localized deformation and cage subsidence while increasing strain energy transfer to ingrown bone tissue reduces the risk of stress shielding. The integrated topology optimization accounting for degradation can be also incorporated in the design for biodegradable/bioabsorbable implants de novo for specific anatomic regions and mechanical loading regimens. This degradation topology optimization creates designs that retain stiffness in the range of trabecular bone through bulk erosion time (240.58 +/- 39.16 MPa; p 0.05).; Biofactor delivery from topology optimized poly(propylene fumarate)/beta-tricalcium phosphate degrading scaffolds was demonstrated in an in vivo immunocompromised murine model. Rapid osteogenesis via BMP-7 transduced cell delivery combined with the designed internal architecture showed that bone formation could be led along the designed contours and the new construct could retain the stiffness at a plateau level of 60 MPa to perform mechanical functions over the implantation time. The results from this study demonstrate the hybrid scaffold/tissue construct could maintain adequate mechanical properties, indicating that physiological forces can be borne by the regenerate bone tissue as the scaffold degrades and loses load carrying capability. These functional results suggest that the integration of optimal scaffold design, fabricated degradable PPF/beta-TCP scaffolds and cell/gene therapy can fulfill the paradigm of functional bone tissue engineering. Therefore, the development of the proposed system for interbody fusion in this work will provide more flexibility for the future spinal fusion approaches and provide a basis for general functional bone tissue engineering.