McKay Orthopaedic Research Laboratory > Mauck Lab > Meniscus Tissue Engineering with Biodegradable Anisotropic Polymer Scaffolds

Meniscus Tissue Engineering with Biodegradable Anisotropic Polymer Scaffolds

Tissue engineering of musculoskeletal structures involves the combination of cells with biodegradable or biocompatible scaffolds. Recently, we have used electrospinning to create fibrous non-woven meshes with nanometer scale fibers that are conducive to cell growth and differentiation [1,2]. While such randomly oriented scaffolds are useful, the majority of naturally occurring tissues exhibit a preferential fiber alignment. This fiber alignment endows tissues with unique functional material properties that vary depending on the testing direction and location. For example, in tendon and ligaments, tensile properties are 200-500 times higher along the fiber direction (over which the force is transmitted) compared to perpendicular to the fiber direction [4]. In articular cartilage, tensile properties are greatest in the superficial zone of the tissue and highest along the prevailing collagen (split line) direction [6,8]. In the meniscus, there exists a distinct collagen architecture with the predominant fibers running circumferentially interspersed with radially directed fibers to ensure tissue integrity [7]. To engineer such complex structures, we have recently described a method for creating anisotropic biodegradable scaffolds by modifying the electrospinning process to incorporate a rotating target onto which fibers are deposited [3,5]. Preliminary findings suggest that the speed of the target dictates the degree of fiber anisotropy within the forming scaffold. This fiber anisotropy in turn determines the mechanical properties of the scaffold. With modest changes in target speed, scaffolds can be produces with a range of anisotropies, from ~4 fold at the slower speed to as much as a 34-fold difference in tensile moduli at the highest speed tested. Cells interact with these anisotropic meshes and cellular morphology follows the prevailing fiber direction. It is hypothesized that by creating an initial architecture, newly formed extracellular matrix will be deposited along the prescribed fiber direction to produce a tissue with the desired functional characteristics. Future studies will investigate the long-term consequences of this prescribed polarity on the engineered construct after the polymeric scaffold has completely degraded, and how physiologic mechanical loading modulates this growth. By tailoring not only polymer composition, but also initial fiber architecture and the mechanical environment, one may more readily produce a tissue construct that recreates the functional anisotropy observed in these tissues in their native form.


Left) Tensile moduli parallel and perpendicular to the spinning direction for meshes produced at varying speeds. *p<0.05 vs. parallel, **p<0.05 vs. parallel at different speed, n=6-8. Right) Meniscal fibrochondrocytes on aligned PCL mesh stained with the Live Dead Assay kit.

References

1. Li WJ, Danielson KG, Alexander PG, Tuan RS, 2003, "Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(epsilon-caprolactone) scaffolds," J Biomed Mater Res, 67A: 1105-14.
2. Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK, 2002, "Electrospun nanofibrous structure: a novel scaffold for tissue engineering," J Biomed Mater Res, 60: 613-21.
3. Li WJ, Mauck RL, Cooper J, Tuan RS, 2004, "Engineering anisotropy in electrospun biodegradable nanofibrous scaffolds for musculoskeletal tissue engineering," 5th Combined Meeting of the Orthopaedic Research Societies of Canada, USA, Japan, and Europe, Alberta, Canada, October 10-13, paper #4.
4. Lynch HA, Johannessen W, Wu JP, Jawa A, Elliott DM, 2003, "Effect of fiber orientation and strain rate on the nonlinear uniaxial tensile material properties of tendon," J Biomech Eng, 125: 726-31.
5. Mauck RL, Li WJ, Yuan X, Tuan RS, 2005, "Meniscus tissue engineering with anistropic biodegradable nanofibrous poly-caprolactone scaffolds," Proceedings of the 51st Annual Orthopaedic Research Society Meeting, Washington, DC, accepted.
6. Mow VC, Guo XE, 2002, "Mechano-electrochemical properties of articular cartilage: their inhomogeneities and anisotropies," Annu Rev Biomed Eng, 4: 175-209.
7. Sweigart MA, Athanasiou KA, 2001, "Toward tissue engineering of the knee meniscus," Tissue Eng, 7: 111-29.
8. Woo SL, Lubock P, Gomez MA, Jemmott GF, Kuei SC, Akeson WH, 1979, "Large deformation nonhomogeneous and directional properties of articular cartilage in uniaxial tension," J Biomech, 12: 437-46.