Look for major advances in orthopedic and other medical treatment based on novel materials and processing techniques that may be combined with stem cells for an order of magnitude improvement in bone and other tissue growth.
“The convergence of medical technologies in the form of bio-device combinations has enormous potential in the orthopedic sector,” says Michael Haider, chief executive officer of BioE, a biomedical company in St. Paul, MN, that provides human stem cells for drug discovery and therapeutic research. Phillips Plastics of Hudson, WI, is developing custom structures designed to enhance the growth of stem cells derived by BioE from human umbilical cord blood.
The therapeutics jointly developed by Phillips and BioE will be used for treatment of osteoporosis and bone fracture of the hip, spine, wrist, arm and leg, as well as repair of damaged joints throughout the body. The specific stem cell market for orthopedic applications could exceed $3 billion within the next 10 years, up from less than $100 million today. Some 75 million Americans suffer from orthopedic problems, which is one of the skyrocketing areas in medical treatment.
Current metallic orthopedic implants, usually titanium, stainless-steel or cobalt-chromium, may only last as long as 10 to 15 years, although some orthopedic surgeons are telling patients metals may last more than 20 years. The goal of the research and new materials is to improve the life of the implants, both through surface treatments that boost bone growth, as well as new systems in which stem cells grow into bones that replace biodegradable plastic structures.
Useful life of some metal implants, such as titanium, can be curtailed because muscle and other tissue does not adhere well to their surface. Significant research has been aimed at solving the problem, including an effort at the University of Arkansas to make titanium biocompatible with a coating of ceramic nanowire.
Late last year, BioE submitted a 510(k) pre-market notification application to the U.S. Food and Drug Administration requesting regulatory clearance for its PrepaCyte-CB Processing System for umbilical cord blood. PrepaCyte-CB is a sterile, three-bag, closed-cell processing system used to separate and collect therapeutically important cells, including stem cells, from human umbilical cord blood. When mixed with cord blood, the proprietary reagent within PrepaCyte-CB rapidly facilitates a negative selection process. This process causes essentially all red blood cells (RBCs) to settle to the bottom of the mixture, leaving significant quantities of viable and unmodified cells.
Promotes Bone Growth
The materials breakthrough from Phillips Plastics is a three-dimensional structure with interconnected pores that are designed to enhance the growth of these cells in orthopedic implants. Three-dimensional structures have already been created by foaming or foam replication. Such processes can lack adequate strength for orthopedic applications and may have other shortcomings, as well.
Bones can grow into the pores in the Phillips structure, creating a strong mechanical grip.
The Phillips Plastics’ approach appears to be unique. Three-dimensional structures are created that incorporate precisely defined intersecting cores. “The key is that we go with two sets of pins and we get three-dimensional connectivity,” says Majid Entezarian, the engineering manager for the R&D group at Phillips’ Technology Center. The structures can be injection molded or cast from metal, ceramics or polymers, either thermoset or thermoplastic.
The big advantage of the Phillips’ structure over currently available alternatives is its strength to weight ratio. An aluminum molded structure, formed under high pressures, can be 500 times stronger than a part made via foam replication, according to Entezarian. The carefully designed architecture of the Phillips structure helps to distribute loads well and creates compression strength.
“The core size can be varied from 100 micrometers to a few centimeters,” says Entezarian. The optimal core size for bone growth may be in the 300 to 400 micrometer range. Pore size is easily varied by changing pin size and the final structure is about half hollow. Phillips Plastics has made about a thousand of the parts shaped like quarter-inch cubes that contain more than 70 pins. Phillips is now developing larger structures. The biggest technical challenges have been creating three-dimensional connectivity within a mold, building tools that allow easy insertion and extraction of the pins and filling the intricate mold cavity to maximize part strength. One of the issues is shrinkage in the powder metal process with metals and ceramics. Shrinkage can approach 20 percent with metals and ceramics, allowing smaller openings.
Phillips has applied for a patent on the technique.
Other significant work is focusing on development of nanocomposite structures of polymers and ceramics that would also serve as orthopedic implants.
One leading example is work underway at the Brown University Div. of Engineering in Providence, RI, with commercial partnerNanovis, Inc. of West Lafayette, IN. The partnership is commercializing nanostructured surfaces, materials and medical devices that improve the interface with bone, soft tissue, nerves and cardiovascular cells.
“Nanocomposites with the closest surface roughness to natural bone at the nano scale promote the most bone cell adhesion and calcium deposition,” says Thomas Webster, associate professor of engineering and orthopedics at Brown. His current efforts focus on replicating bone through creation of three-dimensional structures from titania/PLGA (polylactic-co-glycolic acid) using an aerosol-based three-dimensional printing technique. The structure, already tested in small animals, promotes growth of bone that replaces the bioresorbable PLGA.
“If someone is in a car accident and has a bone scan at the hospital, you can use the exact geometry of the fracture to create an implant through a 3-D printing system,” says Webster.
He’s using 3-D printing systems made by Optomec of Albuquerque, NM. High-powered lasers create structures from powdered metals one layer at a time through a process called additive manufacturing.
Webster’s lab trials go beyond bones. “We are also working on vascular applications, such as stents, the bladder, cartilage and the central nervous system,” he says. “The theme is the same. We look at the new size scale to see if the body recognizes material that has nano roughness.”
Different materials are used in the Optomec system depending on the application.
One specific example described in a recent Materials Research Society paper uses PLGA from Polysciences, Inc. of Warrington, PA, combined with nanophase titania powder from Nanophase Technologies Corp. of Romeoville, IL. The weight ratio is 30/70 ceramic to polymer. The composite suspension is aerosolized in the Optomec system and deposited based on a pre-designed CAD model. The final scaffolds were 1 cm squares with a thickness of 0.5 mm in the case discussed. Porosity of the structure was 32 percent. The percentage of porosity, the pore size and shape can be controlled by the CAD model.
Other important research is ongoing in this area, including a project at MIT in which stem cells grow in polymer scaffolds to form tissues with characteristics of human cartilage, liver, nerves and blood vessels. The engineered scaffold is considered the key element in the system. It provides physical cues for cell orientation and spreading, while pores create space for remodeling of tissue structures.
MIT researchers have tested stem cell interaction with polymers made from 25 different acrylate monomers with what they describe as promising results.
Asked to describe the most important remaining challenges, MIT Professor Robert Langer, who received the 2007 National Medal of Science, says, “From a science standpoint, it’s understanding what are the key material characteristics for controlling stem cell differentiation and growth. And from a medical standpoint — moving to the clinic which will initially mean longer term animal studies in different animal models.”
Potential Industrial Uses for New Medical Scaffold Structures
High-Performance Plastics Target Implant Market