Towards Hydrogel-Capped Metal Implants for Cartilage Repair

Abstract

There are approximately 900,000 people in the US suffering from damage to the articular cartilage, with the knee being most commonly affected. Articular cartilage lacks a vasculature and has a limited ability to heal. A variety of surgical treatments have been developed to repair cartilage lesions. Current strategies for cartilage repair include microfracture, autologous chondrocyte implantation (ACI) and osteochondral allograft transfer (OAT). These strategies suffer from high failure rates (25-50% at 10 years), long rehabilitation times (more than 12 months) and decreasing efficacy in patients older than 40-50 years. Focal joint resurfacing with traditional orthopedic materials is being explored as an alternative strategy, but due to their high stiffness and coefficient of friction relative to cartilage, these implants may ultimately contribute to joint degeneration through abnormal stress and wear. A focal joint resurfacing method that is widely available, allows immediate weight bearing, has short recovery times and has low long-term failure rates remains an unmet need.This thesis explores a strategy to address this need. There are two major criteria within this strategy: 1) develop a material that mimics the properties of cartilage and 2) attach this material to an orthopedic base to enable integration with bone. I developed the first hydrogel to achieve the strength and modulus of cartilage in both tension and compression properties. This hydrogel also exhibits cartilage-equivalent tensile fatigue at 100,000 cycles. The hydrogel was created by infiltrating a PVA-PAMPS double-network hydrogel into a bacterial cellulose (BC) nanofiber network. The BC fibers provide tensile strength in a manner analogous to collagen in cartilage. The PAMPS provides a fixed negative charge and osmotic restoring force similar to the role of aggrecan in cartilage. Subsequently, I further improved and developed the hydrogel to reach a strength that exceeds that of cartilage. The high strength was achieved through reinforcement of crystallized PVA with BC. Experimental results show that reinforcement of annealed PVA with BC leads to a 3.2-fold improvement in the tensile strength (from 15.6 to 50.5 MPa) and a 1.7-fold increase in the compressive strength (from 56.7 to 95.4 MPa). The BC-reinforced PVA was also 3 times more wear resistant than cartilage over 1 million cycles and exhibited the same coefficient of friction. These properties make the BC-reinforced BC hydrogel an excellent candidate material for replacement of damaged cartilage. Current strategies for adhering hydrogel to a surface are 10 times weaker than the shear strength with which cartilage is attached to bone. The osteochondral junction is characterized by mineralized collagen nanofibers anchoring cartilage to bone. I sought to mimic this strategy by bonding freeze-dried BC to porous titanium with a hydroxyapatite-forming cement. The cement penetrates about 10 microns into the bacterial cellulose, forming a nanofiber-reinforced zone of adhesion. The PVA-PAMPS hydrogel is then infiltrated into the bonded bacterial cellulose. This strategy achieved a shear strength of attachment three times greater than the state of the art. I soon proposed an important enhancement of the attaching strategy by introducing shape memory alloy ring to change the direction of shear load bearing. It is the first method for attaching a hydrogel to metal with the same shear strength as the cartilage-bone interface. The average shear strength of the junction between 1.2-mm-thick hydrogel and metal made in this manner exceeded the shear strength of porcine cartilage-bone interface. The shear strength of attachment increased with the number of bacterial cellulose layers and with the addition of cement between the bacterial cellulose layers. Such improved strategies for attaching hydrogels to a metal surface with sufficient strength to allow for weight-bearing can enable the creation of hydrogel-capped titanium implants for cartilage repair.