(207c) Resorbable Polyurethane/bone Composites for Bone Tissue Engineering
AIChE Annual Meeting
Tuesday, November 18, 2008 - 9:20am to 9:45am
There is a recognized need for improved biomaterials that promote orthopedic healing. Traditional care includes metallic rods and bioceramics, which are typically bioinert. These options provide a satisfactory level of clinical outcome for typical civilian applications. However, some cases such as those in the battlefield environment introduce an elevated level of fracture management with challenges such as infection. We are addressing elevated concerns and aim to improve orthopedic fracture management with bone/polymer composite biomaterials that will facilitate fracture reduction and enhance biological healing and biomechanical function.
Composites synthesized from bone and thermoplastic polymers have been shown to remodel in vivo.1 However, the polymers must be heated above the glass transition or melting temperature and compression-molded to achieve high mechanical properties. We are pursuing a reactive liquid molding approach wherein bone/polyurethane composites are mixed and compression-molded at ambient temperature, thus rendering them useful for injectable applications as well. Furthermore, by enhancing the reactivity of the surface of the bone particles, the interfacial binding, and therefore the mechanical properties, can be improved.
We have synthesized bone/polyurethane (PUR) composites from lysine diisocyanate (LDI), polycaprolactone (molecular weight 300) (PCL 300), and mineralized bone powder (100-500 microns) (MBP). Polymers synthesized from LDI and polyester polyols have been reported to support cell attachment and biodegrade to non-cytotoxic degradation products.2-4 We have synthesized composites incorporating 75 wt% MBP over a range of isocyanate indices (index = 100 x NCO:OH equivalent ratio). Mechanical properties were measured using compression and 3-point bending. DMA frequency sweeps have shown that surface demineralization enhances storage modulus by up to 1 GPa. Composites with compression modulus up to 2.5 GPa and compression strengths up to 80 MPa have been prepared. Our results show that index has a large effect on mechanical properties, with a maximum in the modulus occurring at an index of 140. The glass transition temperature was observed to be 65 ¢ªC using DMA, while it was observed to be 51 ¢ªC using DSC. Degradation experiments show that the composites retain greater than 90% of their original mass over a 12 week period, and the rate can be changed by manipulating the backbone of the polyol. In vitro studies have shown that the MBP/PUR composites support MC3T3 osteoprogenitor cell attachment. A 3 rabbit in vivo study was completed in January 2008 in which MBP/PUR composite plugs were implanted into 6 mm femoral defects. The rabbit femurs were extracted, and there were no signs of infection. Histology results are currently being processed to confirm bone resorption. These preliminary studies suggest that MBP/PUR composites are promising biomaterials for bone tissue engineering.
1. Boyce TM, Winterbottom JM, Lee S, Kaes DR, Belaney RM, Shimp LA, Knaack D. Cellular Penetration And Bone Formation Depends Upon Allograft Bone Fraction In A Loadbearing Composite Implant. 2005. p 133.
2. Guelcher SA, Patel V, Gallagher K, Connolly S, Didier JE, Doctor J, Hollinger JO. Synthesis and biocompatibility of polyurethane foam scaffolds from lysine diisocyanate and polyester polyols. Tissue Eng 2006;12(5):1247-1259.
3. Guelcher SA, Gallagher KM, Srinivasan A, McBride SB, Didier JE, Doctor JS, Hollinger JO. Synthesis, in vitro biocompatibility and biodegradation, and mechanical properties of two-component polyurethane scaffolds: effects of water and polyol composition. Tissue Eng In Press.
4. Guelcher SA, Didier JE, Srinivasan A, Hollinger JO. Synthesis, mechanical properties, biocompatibility, and biodegradation of cast poly(ester urethane)s from lysine-based polyisocyanates and polyester triols. Manuscript in preparation.