James A. Cooper

ENGINEERING CONTROLLABLE ANISOTROPY IN ELECTROSPUN BIODEGRADABLE NANOFIBROUS SCAFFOLDS FOR MUSCULOSKELETAL TISSUE ENGINEERING

Many musculoskeletal tissues exhibit significant anisotropic mechanical properties reflective of a highly oriented underlying extracellular matrix. For tissue engineering, recreating this organization of the native tissue remains a challenge. To address this issue, this study explored the fabrication of biodegradable nanofibrous scaffolds composed of aligned fibers via electrospinning onto a rotating target, and characterized their mechanical anisotropy as a function of the production parameters. The characterization showed that nanofiber organization was dependent on the rotation speed of the target; randomly oriented fibers (33% fiber alignment) were produced on a stationary shaft, whereas highly oriented fibers (94% fiber alignment) were produced when rotation speed was increased to 9.3m/s. Non-aligned scaffolds had an isotropic tensile modulus of 2.1+/-0.4MPa, compared to highly anisotropic scaffolds whose modulus was 11.6+/-3.1MPa in the presumed fiber direction, suggesting that fiber alignment has a profound effect on the mechanical properties of scaffolds. Mechanical anisotropy was most pronounced at higher rotation speeds, with a greater than 33-fold enhancement of the Youngs modulus in the fiber direction compared to perpendicular to the fiber direction when the rotation speed reached 8m/s. In cell culture, both the organization of actin filaments of human mesenchymal stem cells and the cellular alignment of meniscal fibroblasts were dictated by the prevailing nanofiber orientation. This study demonstrates that controllable and anisotropic mechanical properties of nanofibrous scaffolds can be achieved by dictating nanofiber organization through intelligent scaffold design.

Biomimetic tissue-engineered anterior cruciate ligament replacement

There are >200,000 anterior cruciate ligament (ACL) ruptures each year in the United States, and, due to the poor healing properties of the ACL, surgical reconstruction with autograft or allograft tissue is the current treatment of these injuries. To regenerate the ACL, the ideal matrix should be biodegradable, porous, and exhibit sufficient mechanical strength to allow formation of neoligament tissue. Researchers have developed ACL scaffolds with collagen fibers, silk, biodegradable polymers, and composites with limited success. Our group has developed a biomimetic ligament replacement by using 3D braiding technology. In this preliminary in vivo rabbit model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regeneration with our cell-seeded, tissue-engineered ligament replacement.

The ABJS Nicolas Andry Award: Tissue engineering of bone and ligament: a 15-year perspective.

Musculoskeletal repair is a major challenge for orthopaedic surgeons. The burden of repair is compounded by supply constraints and morbidity associated with autograft and allograft tissue. We report 15 years of research regarding tissue engineering and biological substitutes for bone and ligaments. Our approach has focused on biomaterial selection, scaffold development, cell selection, cell/material interaction, and growth factor delivery. We have extensively tested poly(ester), poly(anhydride), poly(phosphazene) derivatives, and composite materials using biocompatibility, degradation, and mechanical analyses for bone and ligament tissue engineering. We have developed novel three-dimensional matrices with a pore structure and mechanical properties similar to native tissue. We also have reported on the attachment, growth, proliferation, and differentiation of cells cultured on several scaffolds. Through extensive molecular analysis, in vitro culture condition analysis, and in vivo evaluation, our findings provide new methods of bone tissue regeneration using three-dimensional tissue engineered scaffolds, bioactive bone cement composite materials, and three-dimensional tissue engineered scaffolds for ligament regeneration.The occurrence of proximal humerus fractures will continue to rise with the increasing elderly population. Many patients with proximal humerus fractures have osteoporosis and have poor neuromuscular control mechanisms. This predisposes them to future falls and additional fractures. Patients continue to have shoulder problems as a result of the fracture for many years after the injury. Rehabilitation is central to addressing the problems caused by the fracture. The review of the literature on proximal humerus rehabilitation suggests that treatment must begin immediately if the harmful effects of immobilization are to be avoided. Electrotherapy or hydrotherapy does not enhance recovery and joint mobilization has limited evidence of its efficacy. In the United Kingdom most patients are immobilized routinely for 3 weeks or longer and are referred for physical therapy. The best available evidence for shoulder rehabilitation emphasizes using advice, exercise, and mobilization of limited joints to restore upper limb function. Placing controlled stresses throughout the fracture site at an early stage will optimize bone repair without increasing complication rates. This approach requires cooperation between the referring surgeon and therapist and will optimize the patients shoulder function and maintain their functional independence.Level of Evidence: Diagnostic study, level II (systematic review of level II studies). See the Guidelines for Authors for a complete description of levels of evidence.