Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly L-lactide (PLLA). Part II: practical properties of miniscrews and miniplates.

Miniscrews and miniplates made of forged composites composed of raw hydroxyapatite (u-HA) particles (particle size 0.2-20 microm, averaging 3.0 microm, Ca/p = 1.69 and containing CO3(2-)) and a poly L-lactide (PLLA, Mv: about 180 kDa, containing residual 0.05 wt% lactide) with osteological bioactivity such as direct bonding to bone and osteoconductivity, total resorbability and radiopacity were examined for various mechanical properties in order to evaluate their usefulness for cranio-, oral and maxillo-facial as well as plastic and reconstructive surgeries with PLLA-only or titanium devices. The composites containing u-HA particles at 30wt% for miniscrews and 40wt% for miniplates were selected based on total mechanical strengths and bioactivity, respectively. It was found that the composite devices generally had slightly different mechanical properties than forged PLLA-only devices of which strengths are ranked the highest among the reinforced PLLA-only ones that having been used in many clinical cases to date, in spite of their approximate 2 or 3 times lower absolute strengths than those of titanium ones. However, a remarkable distinction that makes the composite miniplates stand above the titanium ones was confirmed on their fatigue resistance to alternate bendings such that they retained 70% of their initial strength even after 60 times without revealing any damage, whereas the metallic devices fully broke off at only 8 times. This behavior was similar to that of forged PLLA-only devices but is unique as composites made of organic polymers divided by inorganic particles. In addition, profile plates such as L-, T-, X, T, C-, Mesh-, Box-, and Barhole types which were processed by forging twice exhibited nearly directional isotropy in strength and could be deformed in situ at ordinary temperatures to adjust their shapes along the surface undulations of the skull, mandible, maxilla, zygomatic bone and the like without thermoforming and did not return to their original shapes inside an alive body due to the high PLLA's Tg (65 degrees C) over an alive body temperature (37 degrees C). Since it had already been confirmed in previous papers that these stiff and tough composites have the osteological bioactivity which is missing from both PLLA-only and titanium ones, and radiopacity which is wanting in PLLA-only ones, these various small and thin screws and plates have conclusively less objectionable practicality for use in oral-maxillo and craniofacial as well as plastic and reconstructive surgeries.

Biomechanical and morphologic evaluation of a three-dimensional fabric sheep artificial intervertebral disc: in vitro and in vivo analysis.

STUDY DESIGN: We have developed a new artificial intervertebral disc consisting of triaxial three-dimensional fabric for the sheep lumbar spine. To clarify the characteristics of the new implant, a series of biomechanical tests and morphologic evaluations were conducted. OBJECTIVES: To investigate the static, viscoelastic, and fatigue properties of the three-dimensional fabric disc in comparison with natural sheep disc and to evaluate their biomechanical and morphologic alteration in vivo. SUMMARY OF BACKGROUND DATA: In its human dimensions the three-dimensional fabric disc revealed mechanical properties similar to a natural human disc. METHODS: The disc-body units from sheep spine and the sheep three-dimensional fabric discs underwent tensile-compressive (200 N), torsional (5 Nm), and creep-recovery tests (30 minutes-30 minutes, 200 N). After fatigue loading (2 million, compressive 200 N) the biomechanical changes and the debris were investigated. For in vivo evaluation after placing in the sheep psoas muscles for 6 months, the surface of the three-dimensional fabric disc was evaluated using macroscopy and scanning electron microscopy, followed by previous biomechanical tests. RESULTS: The behavior of the sheep three-dimensional fabric disc was similar to that of natural sheep disc in tensile-compressive and creep-recovery tests. In torsional testing the behavior of natural sheep disc was more rigid than that of the sheep three-dimensional fabric disc. After fatigue loading there was no biomechanical change and no debris detected. Six months after surgery no morphologic deterioration was observed nor were there changes in biomechanical parameters. CONCLUSIONS: The sheep three-dimensional fabric disc exhibited biomechanical and morphologic biostability, appropriate viscoelasticity, and excellent fatigue properties. The three-dimensional fabric disc has a potential for clinical application of human intervertebral disc replacement.

Bone bonding ability of a new biodegradable composite for internal fixation of bone fractures.

Hydroxyapatite particles and poly(L-lactide) composites for internal fixation of bone fractures have been developed based on the hypothesis that incorporation of hydroxyapatite particles in a poly(L-lactide) matrix might enhance bone bonding. This study evaluated the bone bonding ability of these biodegradable composites. Two types of hydroxyapatite and poly(L-lactide) composite were used in this study: calcined hydroxyapatite/poly(L-lactide) and uncalcined hydroxyapatite/poly(L-lactide). Rectangular plates (2 x 10 x 15 mm) of each composite or poly(L-lactide) were implanted into the metaphysis of the tibiae of 33 male rabbits, and the failure load was measured by conducting a detaching test 8, 16, and 25 weeks after implantation. The failure loads of calcined hydroxyapatite/poly(L-lactide), uncalcined hydroxyapatite/poly(L-lactide), and poly(L-lactide), respectively, were 13.60, 13.95, and 0.46 N at 8 weeks; 29.84, 24.09, and 2.86 N at 16 weeks; and 25.50, 29.67, and 2.43 N at 25 weeks. Histologic observation revealed that the composites formed direct contact with the bone. The results in this study indicate that the composites improved the strength of the interface between bone and plate. This improved interfacial strength lead to a substantial decrease in the frequency of implant loosening in the treatment of fractured bones by internal fixation.

Biodegradation behavior of ultra-high-strength hydroxyapatite/poly (L-lactide) composite rods for internal fixation of bone fractures.

The purpose of this study was to investigate the biodegradation behavior of the ultra-high-strength hydroxyapatite/poly(L-lactide) (HA/PLLA) composite rods for fracture repair. Two kinds of composite materials were used in this study: u-HA/PLLA. which contained 30% by weight of uncalcined HA as reinforcing particles, and c-HA/PLLA, which contained 30% by weight of calcined HA as reinforcing particles. These composite rods were implanted in the subcutis and in the medullary cavities of rabbits. The specimens were removed at specific intervals between 2 and 52 weeks and the mechanical strength was measured for the rods in the subcutis, and the molecular weight and crystallinity were measured for the rods in both the subcutis and medullary cavities. The rod surfaces were examined using a scanning electron microscope (SEM). The specimens were examined histologically by light microscopy. The bending strength of the composites implanted in the subcutis was maintained at more than 200 M Pa at 25 weeks and at 150 MPa at 52 weeks. The molecular weight dropped to 45% of the initial values at 8 weeks and to approximately 10% at 52 weeks. Significant differences in the molecular weight were seen between c-HA/PLLA and u-HA/PLLA, with u-HA/PLLA showing a faster rate of decrease than c-HA/PLLA after 8 weeks. SEM demonstrated that HA particles disappeared increasingly from the rod surfaces over time and that the spaces left by these HA particles formed many pores in the composite surfaces at 52 weeks. Histologically, a fibrous tissue layer was formed around the composite rod from 4 weeks in the subcutis and in the diaphyseal area of the medullary canal. This became more mature over time. Bony tissue contact to the composites without fibrous tissue layers was seen in the metaphyseal area of the medullary canal. During the experimental period, there were no inflammatory cells such as mono- or multi-nuclear phagocytes. Although further long-term studies for degradation are needed, the composites have promising mechanical strength and no adverse tissue reaction for use as fracture-fixation devices during the experimental periods.

Histomorphometric study on high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures.

The purpose of this study was to investigate the bone-implant interface of high-strength hydroxyapatite (HA)/poly(L-lactide) (PLLA) composite rods. As reinforcing particles, two types of HA particles-calcined HA (c-HA) and uncalcined HA (u-HA)-were applied to allow comparison of their suitability as bioactive fillers. Four types of composites (c-HA30, c-HA40, u-HA30, and u-HA40), which contained 30 or 40% by weight of each HA particle, were used. Unfilled PLLA rods were used as controls. A hole was drilled in the distal femora of 50 rabbits, and a composite or unfilled PLLA rod was implanted in a press-fit manner. Two, 4, 8, and 25 weeks after implantation, the samples were examined histologically by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). An image analyzer was used for histomorphometric analysis of the bone-implant interface. An affinity index was calculated for each material; this was the length of bone directly apposed to the rods expressed as a percentage of the total length of the rod surface. In all the composites, histologic examination showed new bone formation at 2 weeks after implantation. The bone gradually grew along the composite surface. SEM showed direct bone contact with the composites without intervening fibrous tissue. During follow-up, the affinity indices of all the composite rods were significantly higher than those of the unfilled PLLA rods (p < 0.01; two-way ANOVA). The maximum affinity index (41%) was attained at 4 weeks in c-HA40 rods. In contrast, little bone contact was seen in unfilled PLLA rods. The only significant difference in affinity indices among the composites was that c-HA40 had a higher affinity index than u-HA40 (p < 0.05 at 4 weeks). No disintegration of rods or polymer debris, which could elicit inflammatory tissue reactions, was observed even at 25 weeks. Our results indicate that osteoconductive bone formation on composites could enhance the stability between bone and implant in fracture repair.

Biological performance of a three-dimensional fabric as artificial cartilage in the repair of large osteochondral defects in rabbit.

A new artificial cartilage [A three-dimensional fabric (3-DF) comprising ultra-high molecular weight polyethylene fiber with a triaxial three-dimensional structure and coated with hydroxyapatite] was used to repair large osteochondral defects in rabbit knees. The knees with the 3-DF implanted in the osteochondral defects were evaluated 2-24 weeks after the operation macroscopically and microscopically. The 3-DF coated with hydroxyapatite was fixed firmly to the subchondral bone with the newly formed bone into and around the 3-DF. Hyaline-like cartilage was formed to a certain extent on the surface of the 3-DF, and the surface damage of the patella opposed to the 3-DF was minimal. In addition, the 3-DF caused no adverse effects such as particle disease, infection or severe synovitis during the experimental period. Consequently, the 3-DF seems to have successful biocompatibility in this rabbit experiment.

Bonding behavior of ultrahigh strength unsintered hydroxyapatite particles/poly(L-lactide) composites to surface of tibial cortex in rabbits.

Unsintered hydroxyapatite particles/poly(L-lactide) (u-HA/PLLA) composites with an initial bending strength of up to 270 MPa were developed based on the hypothesis that inclusion of u-HA particles in a PLLA matrix might enhance bone bonding. The purpose of this study was to examine the bonding strength and behavior of these u-HA/PLLA composites on the surface of the bone cortex. Composites containing 30 (u-HA30), 40 (u-HA40), or 50 wt % (u-HA50) of fine u-HA particles (3-microm average particle size) were prepared. Semicolumnar plates of these composites and control PLLA plates were fixed with metal screws to the surface of both proximal tibial cortices in 45 rabbits. The loads required to detach the plates from the bone cortex surface, defined as the bonding strengths, were measured at 4, 8, and 25 weeks after implantation. Bonding strengths in the u-HA30 group at 8 weeks and in the u-HA40 and u-HA50 groups at each postimplantation time were significantly greater than in the PLLA group (post hoc test using Fisher's protected least significant difference method). At each postimplantation time histological examinations revealed direct contact between the bone and the u-HA/PLLA composite plates without any intervening fibrous tissue. There was no evidence of any inflammatory or foreign-body response in any group throughout the follow-up periods. The results of this study suggest that the biodegradable PLLA fixation plates amended with u-HA particles could be functionally superior to PLLA plates without particles.

Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lactide (PLLA): Part I. Basic characteristics.

Compounds that had neither calcined nor sintered hydroxyapatite (u-HA) particles (particulate size 0.2-20 microns, averaging 3.0 microns, Ca/P = 1.69, and containing CO3(2-) uniformly distributed in a poly-L-lactide (PLLA, Mv: 400 KDa) matrix with a content of 20-50 wt% (with 10% increment) were reinforced into composites by a forging process, which was a unique compression molding, and were then machined on a lathe in order to produce practical radiopaque internal bone fixation devices having high mechanical strength which was maintained during bony union, total resorbability and bioactivity such as bone bonding capability and osteoconductivity. From the results of measurement of various mechanical properties, it was confirmed that the composites generally showed the highest mechanical strength among this type of reinforced bioceramic fibers or particles/bioresorbable polymer composite known to date. The bending strength (Sb) of about 270 MPa was far higher value than that for cortical bone, and the modulus (Eb) of 12 GPa was almost equivalent to that for cortical bone. In particular, the impact strength (Si) was extremely high at about two times the value (166 KJ/m2) of polycarbonate. The in vitro change in Sb, Mv (viscosity average molecular weight), Mw/Mn (molecular weight distribution) and crystallinity, and their relationship with each other was also examined by immersing samples in a phosphate buffer solution (PBS). An immediate decrease in the initial Mv could be found in composites with high u-HA contents (30-50 wt%), although a time-lag stage for degradation where the initial Mv hardly changes was apparent in cases of PLLA-only or in a composite with a low u-HA content (20 wt%). The Sb changed with corresponding decremental curves for the Mv and retained over 200 MPa for up to 24 weeks, the period of time necessary for full bony union, so that the composite satisfied initial mechanical strengths while maintaining them for as long as necessary for internal bone fixation devices. These results supported the idea that there is a difference in the degradation process such that PLLA alone required a period of time to achieve the possibility of hydrolysis into the inner side, whereas composites with high u-HA contents (30-50 wt%) immediately filled with water through to the inner side and were hydrolyzed homogeneously. Many hydroxyapatite crystals deposited and grew on the surface after 3-6 d and generously covered the surface with a fairly thick layer after 7 d of post-immersion in simulated body fluid (SBF) as evaluated by means of energy dispersive X-ray (EDX). This suggested the ability of the radiopaque composites to bond to bone. Since the composites were dense and had ultra-high strength, and the processability was so excellent, many kinds of fine and accurate screws, pins, plates, and other internal bone fixation devices for orthopedic, oral and maxillofacial, craniofacial, and plastic and reconstructive surgeries could be produced by machining treatment. These devices have potential applications for clinical use following the assessment of adaptation during in vivo studies.

Potential application of a triaxial three-dimensional fabric (3-DF) as an implant.

Various three-dimensional fabrics (3-DFs) woven with a triaxial three-dimensional (3A-3D) structure in which the warps, wefts and vertical fibres are three-dimensionally orientated with orthogonal, off-angle, cylindrical or complex fibre alignments using a single long fibre, which may be one of several kinds of fibres, have been developed. The physical strengths and behaviour of these fabrics under different external forces were measured for such stress-strain relationships as compressive, tensile and cyclic bending, compressing torsional and compressive tensile systems to evaluate the effect of the continuous loading caused by living body movements over a long period of time. The 3-DFs led to downward convex 'J'-shaped curves in stress-strain profiles, because they were markedly flexible at low strain levels, but became rigid as strain increased. In this behaviour they reflected the behaviour of natural cartilage rather than that of conventional artificial biomaterials. There were also some 3-DFs that showed hysteresis loss curves with quite similar mechanical strengths and behaviour to natural intervertebral discs with regard to the compressive-tensile cyclic stress and showed little variation from the first 'J'-shaped hysteresis profile even after 100,000 deformation cycles. Accordingly, it has been shown that, without a doubt, 3-DFs can be effective implants possessing both design and mechanical biocompatibilities as well as the durability necessary for long-term implantation in the living body. The surface of bioinert linear low-density polyethylene coating on multifilaments of ultra-high molecular weight polyethylene, a constructional fibre of 3A-3D weaving, was modified by treatment with corona-discharge and spray-coating of unsintered hydroxyapatite powder to impart chemical (surface) compatibility and biological activity, respectively. Since the modified surface of the 3-DF was ascertained to have affinity and activity with simulated body fluid, an orthogonal 3-DF block was implanted in the tibia of a rabbit. Sufficient surrounding tissues entering into the textural space of the 3-DF could be observed at 4 weeks after implantation and the load necessary to break the block away from the bone reached a high value at 8 weeks. These results decisively showed that the 3-DFs could also acquire chemical (surface) and biological biocompatibilities and bonding capacity with bone and soft tissues through modification of the surface of the constructional fibre. The 3-DFs have definite potential in such applications as novel and effective artificial articular cartilages, intervertebral discs, menisci and materials for osteosynthesis and prosthesis, and the like.

The effects of piezoelectric poly-L-lactic acid films in promoting ossification in vivo.

Uniaxially drawn poly-L-lactic acid (PLLA) films with piezoelectric properties were inserted onto the periosteum of rabbit tibiae, and the effect of the films in promoting ossification was investigated. We also evaluated the optimum method for PLLA film insertion to promote ossification, by comparing three different types of PLLA films which differed from each other in terms of the direction of their molecular orientation. Furthermore, the course of ossification following the film insertion was observed histologically. Drawn PLLA films promoted ossification to a greater extent than undrawn PLLA film. The effect of drawn PLLA films in promoting ossification was greatest when a shearing stress was applied at 45 degrees to the axis of orientation. The newly formed osteoid was observed at 1 week, and matured over 6 to 8 weeks following insertion. The insertion of piezoelectric PLLA films can promote ossification through their piezoelectric effect, and this seems to be clinically applicable.

Enhancement of bone formation by drawn poly(L-lactide).

Poly(L-lactide) (PLLA) was molded into films and rods, and drawn in the longitudinal direction to endow them with piezoelectricity. The piezoelectric constants of PLLA films increased with the draw ratio and, after passing a maximum at a draw ratio around 5, decreased. PLLA samples with a draw ratio 5 underwent fibrilization. The PLLA rods were intramedullarily implanted in the cut tibiae of cats for internal fixation up to 8 weeks. Fracture healing was clearly promoted with increased callus formation as the draw ratio of the PLLA rod increased, whereas the undrawn PLLA as well as a polyethylene control rod had no effect on callus formation, or rather, retarded it. This finding strongly suggests that the promotion of fracture healing by fixation with drawn PLLA can be ascribed to the piezoelectric current generated by the strains accompanying leg movement.

Tissue reaction of bioabsorbable ultra high strength poly (L-lactide) rod. A long-term study in rabbits.

Bioabsorbable ultra high strength poly (L-lactide) rods, which were developed for internal fixation of fractures, were fabricated using a drawing technique. These rods were implanted in the subcutaneous tissue and in the medullary cavity of rabbits to investigate tissue reactions to poly (L-lactide) and to study their degradation process. After 18 months, histiocytes were found, and their phagocytic activity continued for as long as 42 months, with maximum activity observed between 24 and 36 months after implantation. At 62 months after intramedullary implantation, the materials had been absorbed almost completely and were replaced by bone marrow cells, with only a small amount of residual tissue reaction. At 69 months after subcutaneous implantation, the materials had been absorbed completely without any scar formation. During degradation, no foreign body giant cells were found and osteolytic expansion caused by liquid degradable materials was not seen.

Biodegradable plate fixation of rabbit femoral shaft osteotomies. A comparative study.

Femoral shaft transverse osteotomies in 58 rabbits were fixed with ultrahigh strength poly-L-lactic acid plates made by a drawing technique. Similar osteotomies in another 35 rabbits were fixed using stainless steel plates. The union rate, the mechanical strength of the united bones, bone mineral content and density in the area beneath the plate using dual energy x-ray absorptiometry, and the cortical thickness beneath and opposite the plate using a digitizer was compared between the poly-L-lactic acid and stainless steel groups after postoperative periods of 8, 25, and 40 weeks. The poly-L-lactic acid and stainless steel groups showed union rates of 67% (39 of 58) and 80% (28 of 35) without displacement, respectively. In the poly-L-lactic acid group, plate failure occurred in 14% (8 of 58). The mechanical strength of the specimen was restored to a level equal to that on the untreated side by 25 weeks, and cortical thickness and bone mineral content and density were maintained almost normal for 40 weeks in the poly-L-lactic acid group. The stainless steel group showed significantly lower mechanical strength and led to osteopenia because of stress shielding after 25 weeks.

Clinical evaluation of uniaxially oriented poly-L-lactide rod for fixation of experimental femoral diaphyseal fracture in immature cats.

Transverse diaphyseal fractures of the femur were experimentally made in immature cats, and were fixed by an intramedullary pinning technique using an uniaxially oriented poly-L-lactide (PLLA) rod, a biodegradable polymer. The healing process was evaluated radiographically and histologically. Formation of bony callus was completed in 8 weeks, and cortical bony union followed. The remodeling process was then observed form 12 to 16 weeks. The healing process was almost the same as when a metallic implant was used. Abundant periosteal callus formation may be attributable to the lower elasticity of the PLLA rod compared with metallic implants. Since no other abnormalities such as growth deformities were detected, it was concluded that the combined use of a uniaxially oriented PLLA rod and an external splint is clinically useful for the repair of diaphyseal fractures in immature cats.

Application of oriented poly-L-lactide screws for experimental Salter-Harris type 4 fracture in distal femoral condyle of the dog.

The clinical usefulness of biodegradable oriented poly-L-lactide (PLLA) screws for experimental Salter-Harris type 4 fracture in the distal femoral condyle of dogs was evaluated. Bony union of the osteotomized fragment of the condyle was almost completed radiographically and histologically within 1 to 2 months after surgery, suggesting that PLLA screws maintained strength long enough to fix the fragment until bone healing. At 4 to 6 months after surgery, minute fissures were histologically confirmed on the surface of the screw thread, suggesting the early stage of biodegradation and absorption of the polymer. During the observational period, no significant difference between the treated femur and the contralateral non-treated femur in either total femoral length or maximum condyle width was observed, indicating no growth disturbance in the treated femur. From these results it was concluded that the PLLA screw might be an ideal implant for the reduction and fixation of epiphyseal plate fractures such as Salter-Harris type 3 or type 4 fractures.

In vitro and in vivo studies on bioabsorbable ultra-high-strength poly(L-lactide) rods.

Ultra-high-strength poly(L-lactide) (PLLA) rods were fabricated using a drawing technique. Rods with a diameter of 3.2 mm and a draw ratio of 2.5:1 showed initial bending strength and modulus values of 240 MPa and 13 GPa, respectively. The purpose of this study was to investigate the in vitro and in vivo degradation of PLLA rods with a draw ratio of 2.5:1. The greater the rod diameter, the longer the bending strength was maintained in phosphate buffered saline at 37 degrees C. The bending strength retention of rods (diam. 3.2 mm) implanted in the subcutis of rabbits was almost equal to that of rods in the in vitro study, while those rods implanted in the medullary cavity of rabbit femora showed a slightly lower bending strength retention. Molecular weight was reduced to the greatest extent in the medullary cavity, followed by in the subcutis and in vitro. The weight of PLLA rods in the medullary cavity was reduced by 22% at 52 weeks and by 70% at 78 weeks after implantation. Histologically, no inflammatory or foreign body reaction was observed in the medullary cavity for 52 weeks. The drawn PLLA rods maintained a bending strength exceeding that of human cortical bone in the medullary canal for a period of 8 weeks, suggesting that the drawn PLLA rods may be useful in the repair of fractured human bones.

Biodegradable screw fixation of rabbit tibia proximal osteotomies.

The purpose of this study was to evaluate a biodegradable poly(L-lactide) (P-L-LA) screw for osteosynthesis under a load-bearing condition. A proximal tibial osteotomy on 25 rabbits was fixed with a biodegradable screw made of P-L-LA. A follow-up study was done at 1, 2, 4, 8, and 16 weeks. In another 25 rabbits, the tibial osteotomy was fixed with stainless steel (SUS) screws of the same size as the P-L-LA screws with a similar follow-up period. Radiographic, histological, microradiographic, and oxytetracycline-labeling studies showed healing of the osteotomy within 4 to 8 weeks. The displacement of fragments and the mass of newly formed bone around the screws were measured by histomorphometric analysis. There was no significant difference in the displacement of the fragments in these two groups and new bone was more abundantly detected in the P-L-LA group than in the SUS group. Histologically, no inflammatory lesion was detected in either group. All osteotomies united without delay and the displacement was minimal, although no external support was applied and the rabbits were allowed to move freely after the operation. The results of this study suggest a possible use for a P-L-LA screw in the clinical treatment of human bone fractures.