When meniscal tears occur in the avascular region of the meniscus, treatment options are limited. Removing the damaged tissue (resection) is the most common treatment. Although the surgery relieves pain and restores a certain degree of function, it also alters the way mechanical loads are transferred across the joint and often contributes to articular degeneration in the joint.
Engineered biodegradable implants offer a promising alternative to resection, but success with this strategy is still limited. The challenge is to engineer a scaffold construct that not only duplicates the structural and mechanical properties of meniscal tissue, but also enables cellular infiltration necessary for new tissue growth.
Mara L. Schenker, MD, a resident at the Hospital of the University of Pennsylvania, received a 2010 Orthopaedic Research and Education Foundation (OREF) Resident Clinician Scientist Training Grant, which aims to encourage orthopaedic surgery residents to pursue high-quality scientific achievements while they prepare for a career that includes research as a major component. With the grant, Dr. Schenker assessed the degree of cellular infiltration and mechanical integration strength of a nanofibrous implant developed by researchers at the university.
Creating a dual-purpose implant
The mechanical function of the meniscus depends on its dense, avascular construction. But these features, which make it ideal for bearing weight, result in poor healing potential after injury. Even when healing does occur, the scar tissue is often filled with disorganized collagen that offers scant mechanical strength. As Dr. Schenker noted, “At this point, we can offer little to nothing that can slow the cascade of joint degeneration or prevent arthritis down the line.”
Researchers at the University of Pennsylvania’s McKay Orthopaedic Research Laboratory, under the leadership of Robert L. Mauch, PhD, have been developing a nanofibrous scaffold that mimics the scale of the meniscal extracellular matrix, as well as its anisotropic (direction-dependent) architecture. Although these factors impart the scaffold with functional properties comparable to meniscal tissue, the density of the construct limits cellular infiltration.
To address this issue, the researchers modified their design to fabricate a dual-polymer scaffold with discrete fibers of slow- and fast-degrading polymers. The goals of this strategy are to reproduce the architectural and mechanical properties of meniscal tissues primarily with the slow-degrading fibers and to make room for new tissue growth with the fast-degrading fibers.
“We do what’s called electrospinning,” explained Dr. Schenker. “We draw two different types of polymers into an electrical field. They’re collected onto a rotating mandrel, and we get a sheet of dual polymer. We can then fold that into three-dimensional structures for implants.”
Assessing the viability
The 2010 OREF grant supported in vitro and in vivo experiments conducted by Dr. Schenker to assess the utility of the dual-polymer scaffold as a meniscal implant.
In one set of in vivo experiments, dual-polymer scaffold strips were implanted into the dorsal subcutaneous tissues of rats. At several intervals up to 12 weeks, Dr. Schenker examined the cell infiltration, collagen deposition, and mechanical strength of the scaffold. She then compared the results of single-polymer scaffolds with multiple dual-polymer scaffolds (varied by the percent composition of fast-degrading polymer).
In a set of in vitro experiments, dual-polymer scaffolds were formed into three-dimensional cylindrical structures. Sets of scaffolds were placed in the center of a ring of bovine meniscus tissue and cultured. At several intervals up to 8 weeks, Dr. Schenker examined the cell infiltration of the scaffold and the strength of the scaffold-to-meniscus interface. The results of single-polymer scaffolds, dual-polymer scaffolds, and native tissue plugs were then compared.
Dr. Schenker explained the interface testing in this way: “It’s like a donut. The native tissue is the donut, and the scaffold is the donut hole. When a depressor on the instrument pushes the scaffold out, it measures the force required to extrude it from the native meniscus tissue.”
Finally, Dr. Schenker and her team performed in vivo experiments in a sheep model of meniscal defect, to assess the scaffold construct under load-bearing conditions in the knee joint, which could alter both the degree of cellular infiltration and the scaffold-to-tissue integration strength.
Early results of these studies are promising and demonstrate that dual-polymer scaffolds offer improved cellular infiltration, collagen deposition, and integration with surrounding tissues in both in vitro and in vivo environments.
A career in joint preservation
Dr. Schenker’s OREF-supported research is just one step in developing a clinically viable, nanofibrous meniscal implant. But the grant also plays a role in her long-term career plans as a clinician scientist.
“My whole goal for future research is to work on tissues with poor healing potential, including joint preservation models,” she said. “In addition to funding my current study, this grant has been invaluable in learning how to go through the grant-writing process, solicit support for my own investigations, and simply see things from the very beginning to the very end.”
Jay D. Lenn is a contributing writer for OREF and can be reached at email@example.com