Development of a naturally derived biomaterial with controlled regional extracellular matrix heterogeneity for orthopaedic interface regeneration

The repair of interfaces between hard and soft tissues is one of the most challenging problems in orthopaedic medicine. Examples include full thickness articular cartilage defects, ruptured growth plates, and degenerated intervertebral discs. The most prominent clinical manifestation of this orthopaedic challenge is seen in the repair of soft connective tissue (ligament and tendon) ruptures. The contiguous and mechanically functional orthopaedic interface permits smooth load transfer between motion segments in the body. Using current grafts and surgical methods, when injured soft connective tissues are repaired, often the normal structure of the orthopaedic interface fails to regenerate. Tissue engineering may provide an alternative solution. Much of the tissue engineering work for these soft connective tissues, however, has only focused on either the hard or the soft sections of the tissue. To be effective, the orthopaedic interfaces must be recreated to restore proper function and ensure biological integration with the host tissue. To address this challenge, we developed, characterized and modified an orthopaedic interface template derived from natural materials that has a continuous connection between the hard and soft tissue regions and maintains a high level of nutrient transport. Preliminary in vivo studies indicate the formation of a heterogeneous interface similar to that of the normal tendon orthopaedic interface. The results of this work provide solid foundation for the development of a robust, clinically applicable methods to guide the endogenous regeneration of complex tissue structures

Functional MRI can detect changes in intratissue strains in a full thickness and critical sized ovine cartilage defect model

Functional imaging of tissue biomechanics can reveal subtle changes in local softening and stiffening associated with disease or repair, but noninvasive and nondestructive methods to acquire intratissue measures in well-defined animal models are largely lacking. We utilized displacement encoded MRI to measure changes in cartilage deformation following creation of a critical-sized defect in the medial femoral condyle of ovine (sheep) knees, a common in situ and large animal model of tissue damage and repair. We prioritized visualization of local, site-specific variation and changes in displacements and strains following defect placement by measuring spatial maps of intratissue deformation. Custom data smoothing algorithms were developed to minimize propagation of noise in the acquired MRI phase data toward calculated displacement or strain, and to improve strain measures in high aspect ratio tissue regions. Strain magnitudes in the femoral, but not tibial, cartilage dramatically increased in load-bearing and contact regions especially near the defect locations, with an average 6.7% ± 6.3%, 13.4% ± 10.0%, and 10.0% ± 4.9% increase in first and second principal strains, and shear strain, respectively. Strain heterogeneity reflected the complexity of the in situ mechanical environment within the joint, with multiple tissue contacts defining the deformation behavior. This study demonstrates the utility of displacement encoded MRI to detect increased deformation patterns and strain following disruption to the cartilage structure in a clinically-relevant, large animal defect model. It also defines imaging biomarkers based on biomechanical measures, in particular shear strain, that are potentially most sensitive to evaluate damage and repair, and that may additionally translate to humans in future studies.status: publishe