Evaluation of hydroxylapatite/poly (L-lactide) composites: Mechanical behavior C.C. P. M. VerheyenFtitJ. R. de Wijn; C. A. van Blitterswijk: and K. de Groot, *Biomaterials Research Group, Department of Biomaterials, School of Medicine, University uf Leiden; 'Biomaterials Research Group, Division of Orthopaedic Surgery, School of Medicine, Leiden; gBiomaferialsResearch Group, Laboratory for Otobiology and Biocompatibility, School of Medicine, Leiden, The Netherlands
By mixing hydroxylapatite (HA) into L(-)dilactide monomer, prior to polymerization to poly(L-lactide) (PLLA), hydroxylapatite filled poly(L-lactide) composites were obtained. This study reports about the mechanical properties of these composites compared with unfilled PLLA. It was concluded that a 30 wt% HA/PLLA composite has better compressive and tensile strengths, higher stiffness and Vickers hardness number than unfilled PLLA (Mv: 125-150,000). Gas sterilization (ethylene oxide) affects molecular weight and flexural strength significantly. Im-
plantation studies revealed loss of 50% of initial flexural strength within 3 weeks, and a faster decline of flexural strength was observed in phosphate buffered saline than in the subcutis of goats. From a mechanical point of view storage at -20°C proved to be a safe method. In its current state HA/PLLA composites can not be used as implant materials that have to resist major forces. However, such composites might be useful in nonloadbearing applications in orthopedic or maxillofacial surgery. 0 1992 John Wiley & Sons, Inc.
INTRODUCTION
Treatment of fractures regularly involves surgical intervention by osteosynthetic fixation. There is a mismatch between Young's modulus of cortical bone (7-30 GPa, depending on age, orientation, and location') and the metals commonly used for internal fixation devices (Titanium: 110 GPa, 316Lsteel: 200 GPa). In the concept of rigid fixation of fractures by compression plating' no attempt is made to match the plate rigidity with the physiological needs of the skeletal system. Therefore stress protection at the fracture site prevents rapid proliferation of primary callus. Due to stress protection the long-term result can be a mechanically inferior bone structure in the region of the plate, because of osteoporosis and a t r ~ p h yOther .~ drawbacks are patient sensitization to the metals used and the usually necessary removal by a second operation with disadvantages as refracture, infection risk, pain, and expenses. A resorbable material that possesses mechanical properties that allow for sufficient support during the healing period, still permits uneventful healing by primary callus formation and resorbs in time would be a con$To whom correspondence should be addressed at Department of Biomaterials, Bld.55, School of Medicine, University of Leiden, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands. Journal of Biomedical Materials Research, Vol. 26, 1277-1296 (1992) CCC 0021-9304/92/101277-20$4.00 0 1992 John Wiley & Sons, Inc.
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siderable improvement as an internal fixation device. This would overcome the classical paradox that rigid fixation is often required to achieve union while flexibility is necessary to restore normal mechanical properties of bone after union. Bone healing is a dynamic process, and therefore fixation devices should ensure a progressive load transfer to the bone. Several workers have tested polymers that more or less meet these requirements. Poly(a-hydroxy acids) like poly(t-lactide) (PLLA), polyglycolide (PGA), and polydioxanone (PDS) are a group of materials which are under thorough investigation because of their biocompatibility, bioresorption, and mechanical characteristics. These materials are beginning to be clinically used in case of connective tissue injuries, as bone augments and for the fixation of fracture~.~ The - ~ introduction of polyglactin 910," copolymer consisting of approximately 90% glycolide and 10% L-lactide, self-reinforced with fibers of the same composition, and Biofix (C); self-reinforced PGA, as materials for fracture fixation devices were of significant importance. Uncomplicated fracture healing was also seen after fixation of unstable zygomatic fractures with osteosynthetic devices made of high molecular weight PLLA.6 Hydroxylapatite is the crystalline portion of natural bone mineral. In contact with bone, synthetic HA often develops a mechanically tight bond with bone* which may be of a chemical nature."" Synthetic HA is biocompatible" and osteoconductive. There is a difference of opinion about whether HA is degradable or A major disadvantage is that the sintered material is too brittle and has insufficient strength and fatigue resistance for use in weightbearing situations. Because metals are too stiff to prevent stress protection, ceramics are too brittle and polymers tend to be too flexible and too weak to meet the mechanical demands for an internal fixation device, composites of polymers and inorganic materials may offer the desired compromise. Recently attention has been paid to the application of hydroxylapatite (HA) in combination with a polymeric substance. The use is still confined to the field of the filling of bony defects and as a drug carriersT3P~lyethylene,'~ polybutyrate," and PLLA7," are the most frequently used polymers in such composite materials. Adding HA, as a filler, to a (resorbable) polymer, is expected to increase the initial stiffness of the polymer without too much impact on the strength characteristics. Such a composite would, in this sense, resemble cortical bone which is a calcium mineral reinforced polymer (collagen) composite it~e1f.I~ Our interest is focused on a HA/PLLA-composite material, combining bone bonding potentials (HA) with a considerable initial strength and stiffness, gradually losing its strength while resorbing (PLLA). In this study the mechanical properties of such composites were assessed. MATERIALS
Composite preparation Hydroxylapatite powder with atomic Ca/P ratio of 1.67 was supplied by Merck (Darmstadt, Germany). The powders were granulated and sintered for
MECHANICAL BEHAVIOR OF HA/PLLA COMPOSITES
1279
6 h at 1250°C under 95% nitrogen/5% hydrogen atmosphere. Then the granules were crushed, milled, and sieved to
By mixing hydroxylapatite (HA) into L(-)dilactide monomer, prior to polymerization to poly(L-lactide) (PLLA), hydroxylapatite filled poly(L-lactide) composites were obtained. This study reports about the mechanical properties of these composites compared with unfilled PLLA. It was concluded that a 30 wt% HA/PLLA composite has better compressive and tensile strengths, higher stiffness and Vickers hardness number than unfilled PLLA (Mv: 125-150,000). Gas sterilization (ethylene oxide) affects molecular weight and flexural strength significantly. Im-
plantation studies revealed loss of 50% of initial flexural strength within 3 weeks, and a faster decline of flexural strength was observed in phosphate buffered saline than in the subcutis of goats. From a mechanical point of view storage at -20°C proved to be a safe method. In its current state HA/PLLA composites can not be used as implant materials that have to resist major forces. However, such composites might be useful in nonloadbearing applications in orthopedic or maxillofacial surgery. 0 1992 John Wiley & Sons, Inc.
INTRODUCTION
Treatment of fractures regularly involves surgical intervention by osteosynthetic fixation. There is a mismatch between Young's modulus of cortical bone (7-30 GPa, depending on age, orientation, and location') and the metals commonly used for internal fixation devices (Titanium: 110 GPa, 316Lsteel: 200 GPa). In the concept of rigid fixation of fractures by compression plating' no attempt is made to match the plate rigidity with the physiological needs of the skeletal system. Therefore stress protection at the fracture site prevents rapid proliferation of primary callus. Due to stress protection the long-term result can be a mechanically inferior bone structure in the region of the plate, because of osteoporosis and a t r ~ p h yOther .~ drawbacks are patient sensitization to the metals used and the usually necessary removal by a second operation with disadvantages as refracture, infection risk, pain, and expenses. A resorbable material that possesses mechanical properties that allow for sufficient support during the healing period, still permits uneventful healing by primary callus formation and resorbs in time would be a con$To whom correspondence should be addressed at Department of Biomaterials, Bld.55, School of Medicine, University of Leiden, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands. Journal of Biomedical Materials Research, Vol. 26, 1277-1296 (1992) CCC 0021-9304/92/101277-20$4.00 0 1992 John Wiley & Sons, Inc.
VERHEYEN ET AL.
1278
siderable improvement as an internal fixation device. This would overcome the classical paradox that rigid fixation is often required to achieve union while flexibility is necessary to restore normal mechanical properties of bone after union. Bone healing is a dynamic process, and therefore fixation devices should ensure a progressive load transfer to the bone. Several workers have tested polymers that more or less meet these requirements. Poly(a-hydroxy acids) like poly(t-lactide) (PLLA), polyglycolide (PGA), and polydioxanone (PDS) are a group of materials which are under thorough investigation because of their biocompatibility, bioresorption, and mechanical characteristics. These materials are beginning to be clinically used in case of connective tissue injuries, as bone augments and for the fixation of fracture~.~ The - ~ introduction of polyglactin 910," copolymer consisting of approximately 90% glycolide and 10% L-lactide, self-reinforced with fibers of the same composition, and Biofix (C); self-reinforced PGA, as materials for fracture fixation devices were of significant importance. Uncomplicated fracture healing was also seen after fixation of unstable zygomatic fractures with osteosynthetic devices made of high molecular weight PLLA.6 Hydroxylapatite is the crystalline portion of natural bone mineral. In contact with bone, synthetic HA often develops a mechanically tight bond with bone* which may be of a chemical nature."" Synthetic HA is biocompatible" and osteoconductive. There is a difference of opinion about whether HA is degradable or A major disadvantage is that the sintered material is too brittle and has insufficient strength and fatigue resistance for use in weightbearing situations. Because metals are too stiff to prevent stress protection, ceramics are too brittle and polymers tend to be too flexible and too weak to meet the mechanical demands for an internal fixation device, composites of polymers and inorganic materials may offer the desired compromise. Recently attention has been paid to the application of hydroxylapatite (HA) in combination with a polymeric substance. The use is still confined to the field of the filling of bony defects and as a drug carriersT3P~lyethylene,'~ polybutyrate," and PLLA7," are the most frequently used polymers in such composite materials. Adding HA, as a filler, to a (resorbable) polymer, is expected to increase the initial stiffness of the polymer without too much impact on the strength characteristics. Such a composite would, in this sense, resemble cortical bone which is a calcium mineral reinforced polymer (collagen) composite it~e1f.I~ Our interest is focused on a HA/PLLA-composite material, combining bone bonding potentials (HA) with a considerable initial strength and stiffness, gradually losing its strength while resorbing (PLLA). In this study the mechanical properties of such composites were assessed. MATERIALS
Composite preparation Hydroxylapatite powder with atomic Ca/P ratio of 1.67 was supplied by Merck (Darmstadt, Germany). The powders were granulated and sintered for
MECHANICAL BEHAVIOR OF HA/PLLA COMPOSITES
1279
6 h at 1250°C under 95% nitrogen/5% hydrogen atmosphere. Then the granules were crushed, milled, and sieved to
