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Biomedical subjects

Catherine G Ambrose

Publications and source records attributed to Catherine G Ambrose.

At least 19 recordsLinked to original sources

Effect of calcium tablets on interpretation of lumbar spine DXA scans.

Undissolved calcium (Ca) tablets in the gastrointestinal tract at the time of a dual-energy X-ray absorptiometry (DXA) scan could conceivably affect the accuracy of the lumbar spine bone mineral density (BMD) determination. We studied phantoms and volunteers to determine the effect of Ca tablets overlying bone, Ca tablets in the soft-tissue field, and Ca tablets overlapping both bone and soft tissue. For L1-4, a 500-mg Ca tablet taped to the phantom surface or the skin of volunteers resulted in <or=2.2% mean increase in measured BMD (less than the lumbar spine least significant change), changing the T-score for L1-4 very little. However, an overlying Ca tablet had a substantial effect on BMD of a single vertebral body. Greater effects were seen with higher amounts of tablet Ca and with lower BMD, resulting in as much as a 12.6% mean increase in single vertebral BMD in the in vivo series. Recent versions of DXA software successfully identified tablets in the soft-tissue field as artifact and eliminated the tablet pixels from the analysis. However, tablets overlapping bone and soft tissue necessitated operator intervention to either exclude the affected vertebral body or adjust edges by mapping the tablet as artifact and/or neutral field. A paraffin-coated Ca tablet swallowed by a volunteer was tracked serially by DXA during gastrointestinal transit. Similar effects were seen as with the phantom and volunteer studies using external tablets; there was little effect of the Ca tablet on L1-4 BMD either with the tablet overlying bone or in the soft-tissue field. We conclude that undissolved Ca tablets introduce small artifacts on L1-L4 BMD insufficient to alter diagnostic categorization of patients. However, if only two or three vertebral levels are available, misclassification of the patients may occur due to tablet artifact. The precision of monitoring BMD over time could also be adversely affected by tablet artifact if a tablet was directly overlying bone and undetected, especially with smaller regions of interest and with lower baseline BMD.

Absorptiometry, Photon↗

Functional significance of bone density measurements in children with osteogenesis imperfecta.

BACKGROUND: The treatment of osteogenesis imperfecta has been directed at improvement of bone mineral density, yet the importance of bone mineral density in predicting functional and clinical outcome in this patient population has not been demonstrated. We used a validated functional outcome measure to identify the relationship between bone mineral density and physical function in children with osteogenesis imperfecta, and we also evaluated the relationship of bone mineral density to the rate of surgery and fracture in patients with osteogenesis imperfecta. METHODS: Twenty patients (age range, four to seventeen years) with osteogenesis imperfecta who had undergone bone mineral densitometry as measured by dual x-ray absorptiometry of the lumbar spine, wrist, and proximal aspect of the femur between November 1999 and April 2001 were retrospectively analyzed. Functional outcome was measured with use of the Pediatric Outcomes Data Collection Instrument. These questionnaires were completed by the parents of all twenty patients and, in addition, by fifteen patients in the study who were between the ages of eleven and eighteen years. Fracture and surgery rates were calculated on the basis of the number of documented fractures and surgical procedures that the patient had had from the time of the initial presentation until the time of the latest follow-up visit. RESULTS: There were significant relationships between the bone mineral density of the lumbar spine and the scores obtained on the parent-completed questionnaires with regard to upper-extremity functioning (r = 0.57, p < 0.01), transfers and basic mobility (r = 0.55, p = 0.01), sports and physical functioning (r = 0.55, p = 0.01), and global functioning (r = 0.60, p < 0.004). There were also significant relationships between the bone mineral density of the wrist and the scores obtained on the child-completed questionnaires with regard to upper-extremity functioning (r = 0.82, p < 0.01), sports and physical functioning (r = 0.76, p < 0.01), and global functioning (r = 0.83, p = 0.001). There were significant negative relationships between the bone mineral density of the lumbar spine and the rate of fractures (r = -0.69, p < 0.001) and the bone mineral density of the lumbar spine and the rate of surgery (r = -0.60, p < 0.01). CONCLUSIONS: There is a relationship between bone mineral density and the functional outcome, rate of fracture, and rate of surgery in patients with osteogenesis imperfecta. Bone mineral density appears to be an indicator of disease severity and may be predictive of long-term functional outcome. To establish specific guidelines for treatment, more data on normative bone-mineral density in children with osteogenesis imperfecta will be needed.

Adolescent↗

Flow perfusion culture of marrow stromal cells seeded on porous biphasic calcium phosphate ceramics.

Calcium phosphate ceramics have been widely used for filling bone defects to aid in the regeneration of new bone tissue. Addition of osteogenic cells to porous ceramic scaffolds may accelerate the bone repair process. This study demonstrates the feasibility of culturing marrow stromal cells (MSCs) on porous biphasic calcium phosphate ceramic scaffolds in a flow perfusion bioreactor. The flow of medium through the scaffold porosity benefits cell differentiation by enhancing nutrient transport to the scaffold interior and by providing mechanical stimulation to cells in the form of fluid shear. Primary rat MSCs were seeded onto porous ceramic (60% hydroxyapatite, 40% beta-tricalcium phosphate) scaffolds, cultured for up to 16 days in static or flow perfusion conditions, and assessed for osteoblastic differentiation. Cells were distributed throughout the entire scaffold by 16 days of flow perfusion culture whereas they were located only along the scaffold perimeter in static culture. At all culture times, flow perfused constructs demonstrated greater osteoblastic differentiation than statically cultured constructs as evidenced by alkaline phosphatase activity, osteopontin secretion into the culture medium, and histological evaluation. These results demonstrate the feasibility and benefit of culturing cell/ceramic constructs in a flow perfusion bioreactor for bone tissue engineering applications.

Animals↗

Relationship among MRTA, DXA, and QUS revisited.

Inexpensive, commercially produced devices that directly measure bone strength in vivo are not currently available. Mechanical response tissue analysis (MRTA), a unique prototype device, is an in vivo vibrational test that measures transverse bending stiffness (a measure of whole bone strength expressed as the product of estimated Young's modulus of elasticity and cross-sectional moment of inertia, EI, Nm2) at ulna midshaft. We compared speed of sound (SOS; [m/s]) in ulna cortical bone using a commercially available axial transmission quantitative ultrasound (QUS) device with EI using MRTA. Dual-energy X-ray absorptiometry (DXA) was used to provide an estimate of ulna size (cm2), bone mineral content (BMC; [g/cm]) and areal bone mineral density (BMD; [g/cm2]). The objective of the study was to determine if ulna SOS--alone or in combination with BMD from DXA--was correlated with ulna EI, thus becoming a surrogate measure of transverse bending stiffness, and thus whole bone strength. Data were collected from 138 female volunteers (18-86 yr). EI and SOS were significantly correlated, r = +0.218, p = 0.01, but r2 was very low, 4.8%. SOS and total ulna BMD were combined to estimate elastic modulus, which correlated with EI, r = +0.377, p < 0.0001; however, the correlation was not significantly better than with SOS alone. We conclude that axial transmission QUS is not a strong surrogate in vivo technique for estimating transverse bending stiffness.

Absorptiometry, Photon↗

In vitro osteogenic differentiation of marrow stromal cells encapsulated in biodegradable hydrogels.

Novel hydrogel materials based on oligo(poly(ethylene glycol) fumarate) (OPF) crosslinked with a redox radical initiation system were recently developed in our laboratory as injectable cell carriers for orthopedic tissue engineering applications. The effect of OPF hydrogel material properties on in vitro osteogenic differentiation of encapsulated rat marrow stromal cells (MSCs) with and without the presence of osteogenic supplements (dexamethasone) was investigated. Two OPF formulations that resulted in hydrogels with different swelling properties were used to encapsulate rat MSCs (seeding density approximately 13 million cells/mL, samples 6 mm diameter x 0.5 mm thick before swelling) and osteogenic differentiation in these constructs over 28 days in vitro was determined via histology and biochemical assays for alkaline phosphatase, osteopontin and calcium. Evidence of MSC differentiation was apparent over the culture period for samples without dexamethasone, but there was large variability in calcium production between constructs using cells of the same source. Differentiation was also seen in samples cultured with osteogenic supplements, but calcium deposition varied depending on the source pool of MSCs. By day 28, osteopontin and calcium results suggested that, in the presence of dexamethasone, OPF hydrogels with greater swelling promoted embedded MSC differentiation over those that swelled less (43.7 +/- 16.5 microg calcium/sample and 16.4 +/- 2.8 microg calcium/sample, respectively). In histological sections, mineralized areas were apparent in all sample types many microns away from the cells. These experiments indicate that OPF hydrogels are promising materials for use as injectable MSC carriers and that hydrogel swelling properties can influence osteogenic differentiation of encapsulated progenitor cells.

Alkaline Phosphatase↗

Bioabsorbable implants: review of clinical experience in orthopedic surgery.

Bioabsorbable implants are widely used in orthopedic surgery today and the worldwide market is expanding rapidly. Despite the popularity of these implants, reports of complications continue to appear in the literature. Although the complications rarely have an adverse affect on long-term outcomes, the reports are too numerous to be mere isolated incidents related to one specific implant. Complications have been reported with most of the commercially available implant materials with varying incidence rates and severities of reactions to the implants. The purpose of this review is to summarize the adverse events that have been reported in clinical trials of bioabsorbable implants in orthopedic surgery.

Absorbable Implants↗

Effective treatment of osteomyelitis with biodegradable microspheres in a rabbit model.

Biodegradable microspheres were manufactured from a high molecular weight copolymer of 50% lactic and 50% glycolic acid and the antibiotic tobramycin. It was hypothesized that the microspheres would be more effective than polymethylmethacrylate beads in the local delivery of tobramycin and that the microspheres would not inhibit bone healing. Osteomyelitis was established in 40 New Zealand White rabbits using Staphylococcus aureus. All animals had irrigation and debridement of the infected radii four weeks after inoculation and were divided into five treatment groups: debridement alone, microspheres alone, microspheres containing tobramycin plus parenteral treatment with cefazolin, polymethylmethacrylate beads containing tobramycin plus parenteral cefazolin, and parenteral cefazolin. All animals were sacrificed after 4 weeks of treatment. The group treated with microspheres plus parenteral antibiotics was the only group to have a significantly higher percentage of animals without bacteria after 4 weeks of treatment when compared with the control group. Additionally, the animals treated with microspheres had a higher degree of bone healing in the defect than the animals treated with bone cement. The most effective treatment was biodegradable microspheres combined with parenteral antibiotic in this rabbit osteomyelitis model.

Animals↗

Evaluation of thermal- and photo-crosslinked biodegradable poly(propylene fumarate)-based networks.

Biodegradable networks of poly(propylene fumarate) (PPF) and the crosslinking reagent poly(propylene fumarate)-diacrylate (PPF-DA) were prepared with thermal- and photo-initiator systems. Thermal-crosslinking was performed with benzoyl peroxide (BP), which is accelerated by N,N-dimethyl-p-toluidine (DMT) and enables injection and in situ polymerization. Photo-crosslinking was accomplished with bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO), which is activated by long-wavelength UV light and facilitates material processing with rapid manufacturing techniques, such as stereolithography. Networks were evaluated to assess the effects of the initiators and the PPF/PPF-DA double bond ratio on the mechanical properties. Regardless of the initiator system, the compressive properties of the PPF/PPF-DA networks increased as the double bond ratio decreased from 2 to 0.5. BAPO/UV-initiated networks were significantly stronger than those formed with BP/DMT. The compressive modulus of the photo- and thermal-crosslinked PPF/PPF-DA networks ranged from 310 +/- 25 to 1270 +/- 286 MPa and 75 +/- 8 to 332 +/- 89 MPa, respectively. The corresponding fracture strengths varied from 58 +/- 7 to 129 +/- 17 MPa and 31 +/- 13 to 105 +/- 12 MPa. The mechanical properties were not affected by the initiator concentration. Characterization of the network structures indicated that BAPO was a more efficient initiator for the crosslinking of PPF/PPF-DA, achieving a higher double bond conversion and crosslinking density than its BP counterpart. Estimated average molecular weights between crosslinks (Mc) confirmed the effects of the initiators and PPF/PPF-DA double bond ratio on the mechanical properties. This work demonstrates the capability to control the properties of PPF/PPF-DA networks as well as their versatility to be used as an injectable material or a prefabricated implant.

Biocompatible Materials↗

Mechanical testing of small fracture implants for comparison of insertion and failure torques.

INTRODUCTION: Small fracture screws are among the most commonly used implants in the field of orthopedic surgery. The goal of this study was to compare the insertion and failure torques of three screw types: cortical, partially threaded cancellous, and fully threaded cancellous from three manufacturers: Zimmer, Richards, and Synthes. MATERIALS AND METHODS: Each type of screw was subjected to biomechanical tests to determine the insertion ( n=6/group) and failure ( n=10/group) torques. RESULTS: Two-factor ANOVA tests were run to determine whether the insertion or failure torques were different for the different screw types and manufacturers. In the case of insertion torques, neither the screw nor the manufacturer had any significant effect. In the case of failure torque, significant differences were found based on both the screw type and the manufacturer, with the cortical screws manufactured by Zimmer being the strongest. Although there were strength differences, the most important comparison clinically is between the failure torque and the insertion torque of each screw. In all cases, the failure torques were approximately 20 times larger than the insertion torques, and therefore no failures should occur if only torsional loads are applied during insertion. This comparison shows that factors other than screw strength and manufacturing processes may be involved in cases of screw failure during insertion. CONCLUSION: All three screw types from all three manufacturers appear to be mechanically reliable, with the proper insertion to failure torque ratio. The surgeon's choice of implant should be based on other considerations.

Analysis of Variance↗

In vitro degradation of polymeric networks of poly(propylene fumarate) and the crosslinking macromer poly(propylene fumarate)-diacrylate.

Polymeric networks of poly(propylene fumarate) (PPF) crosslinked with poly(propylene fumarate)-diacrylate (PPF-DA) are currently being investigated as an injectable, biodegradable bone cement. This study examined the effect of crosslinking density, medium pH, and the incorporation of a beta-tricalcium phosphate (beta-TCP) filler on the in vitro degradation of PPF/PPF-DA. Cylindrical specimens were submerged in buffered saline at 37 degrees C and the change in weight, geometry, and compressive mechanical properties were monitored over a 52-week period. All formulations showed an initial increase in modulus and yield strength over the first 12 weeks, achieving maxima of 1307+/-101 and 51+/-3MPa, respectively, for the beta-TCP composite. PPF/PPF-DA networks with the lower crosslinking density demonstrated the greatest degradation with a 17% mass loss. Samples in the lower buffer pH 5.0 compared to physiological pH 7.4 did not show any differences in mass loss, but exhibited a faster decrease in the compressive strength over time. The beta-TCP composites maintained their mechanical properties at the level following their initial increase. These results show that the degradation of PPF/PPF-DA networks can be controlled by the crosslinking density, accelerated at a lower pH, and prolonged with the incorporation of the beta-TCP filler.

Acrylates↗

Fabrication of poly(propylene fumarate)-based orthopaedic implants by photo-crosslinking through transparent silicone molds.

This work presents a new molding process for photo-crosslinked, degradable polymeric networks of poly(propylene fumarate) (PPF) and the crosslinking agent poly(propylene fumarate)-diacrylate (PPF-DA). Transparent room temperature vulcanizing silicone molds were fabricated for parts ranging from simple test coupons to orthopaedic implants. The PPF/PPF-DA resin blend was injected into the cavity and photo-crosslinked as light was transmitted through the mold wall. The volumetric shrinkage, mechanical properties, and the effects of gamma sterilization were reported for molded PPF/PPF-DA networks prepared with varying compositions of the two polymer components. The shrinkage decreased while the mechanical properties displayed a general increasing trend when more of the crosslinking agent was incorporated into the network. Gamma irradiation resulted in an improvement of the mechanical properties. In addition, PPF/PPF-DA replicates of a 70:30 poly(L/DL-lactide) biodegradable fixation plate and a bone allograft interbody fusion spacer were produced to evaluate the performance of PPF/PPF-DA as an orthopaedic implant and allow for a comparison to be made with materials that have been established for clinical use.

Absorbable Implants↗

Constrained acetabular cups: a cadaveric biomechanical evaluation.

Reports indicate that constrained acetabular cups may reduce range of motion and catastrophically fail, although the biomechanics of dislocation have not been reported. We measured the available motion in 6 constrained cups (from 2 manufacturers) when anatomically placed in cadaver pelves. We measured the torque and rotation necessary to dislocate the hip. Range of motion was measured using a custom jig and revealed a functional range of motion with all cup positions. Extension was limited to 0 degrees with anteversion of 11 degrees to 29 degrees. Thus, anteversion of <10 degrees is recommended. Torque and rotation to produce dislocation was 7 ft-pounds and 11 ft-pounds and 82 degrees and 72 degrees, for each manufacturer. Torques were reduced with subsequent dislocations. We recommend consideration of polyethylene replacement if dislocation occurs. Dislocation occurred at the ball-polyethylene interface without catastrophic failure.

Acetabulum↗

Antibiotic microspheres: preliminary testing for potential treatment of osteomyelitis.

Osteomyelitis is a difficult problem for orthopaedic surgeons. The current standard of treatment requires high doses of antibiotic to be administered parenterally, which can damage vital organs. A local drug delivery system, which targets only the infected tissues, would eliminate some of the complications associated with extended courses of parenteral antibiotic treatment. In the current study, biodegradable microspheres were manufactured from a high molecular weight copolymer of 50% lactic and 50% glycolic acid and the antibiotic tobramycin. Various formulations of microspheres were tested for in vitro elution characteristics to determine the optimum formulation for linear release of antibiotic for at least 4 weeks. The optimal formulation then was implanted into a pouch created in the quadriceps muscle of mice to evaluate the in vivo elution of the antibiotic and the inflammatory response elicited by the microspheres. Results indicate that a sustained linear release of antibiotic from the microspheres is possible for a period of at least 4 weeks and that the inflammatory response was within levels required for the microspheres to be considered biocompatible.

Animals↗

Effect of physiological temperature on the mechanical properties and network structure of biodegradable poly(propylene fumarate)-based networks.

Poly(propylene fumarate) (PPF)-based networks have exhibited increases in mechanical properties during their initial stages of degradation. This study was designed to investigate whether physiological temperatures are the source of this reinforcing behavior by influencing the formation of additional crosslinks within the network. Utilizing a model PPF network formed with the crosslinking agent poly(propylene fumarate)-diacrylate (PPF-DA), cylindrical specimens were stored in an inert environment and conditioned at -20 and 37 degrees C while their mechanical properties and network structure were monitored over a six week period. The PPF/PPF-DA specimens exposed to physiological temperatures showed an increase in compressive modulus from 1674 +/- 88 to 2059 +/- 75 MPa. The double bond conversion improved as well, from 64 +/- 1 to 70 +/- 1%, indicating that crosslinks were being formed in the network. The additional reactivity occurred exclusively with unreacted fumarate bonds. PPF/PPF-DA networks stored at -20 degrees C showed no changes in mechanical properties; however, they increased when subsequently conditioned at 37 degrees C. The results were used to explain that PPF-based networks undergo a biphasic degradation behavior due to the competing hydrolytic degradation and thermal induced crosslinking. In addition, heat treating the networks at higher temperatures can be utilized as a means to further reinforce PPF-based materials.

Biocompatible Materials↗

Tendon transfer fixation in the foot and ankle: a biomechanical study evaluating two sizes of pilot holes for bioabsorbable screws.

The purpose of this study was to compare the initial fixation strengths of bioabsorbable screws for tendon transfers in the foot and ankle when the pilot hole size varied. A 7 x 20 mm screw was used with 5.5 mm and 6.5 mm drill holes, and a 5 x 20 mm screw was used with 3.9 mm and 4.5 mm drill holes. Biomechanical testing was performed on each tendon transfer in cadaver specimens. A paired t-test showed no significant difference in pullout strength when pilot hole size varied between 79 to 93% of the screw size for the 7 mm screw and 78 to 90% of the screw size for the 5 mm screw. Previous studies have found a critical value of tendon tension equaling 50 N with passive dorsiflexion of the foot. With an average value of approximately 170 N, the 7 mm screw provided three times the requisite strength. The 5 mm screw provided 1.5 times the requisite strength, but the transfer was technically more difficult.

Absorbable Implants↗

Undertreatment of osteoporosis in men with hip fracture.

BACKGROUND: Women are not aggressively treated for osteoporosis after hip fracture; the treatment status of men with hip fracture has not been extensively studied. OBJECTIVE: To evaluate the outcome and treatment status of men with hip fracture. METHODS: Data from medical records were obtained for 363 patients (110 men and 253 women) aged 50 years and older with atraumatic (low-energy) hip fracture who were admitted to St Luke's Episcopal Hospital between January 1, 1996, and December 31, 2000. Surveys were mailed to surviving patients. Main outcome variables were osteoporosis treatments (antiresorptive or calcium and vitamin D) at hospital discharge, current osteoporosis treatments at 1- to 5-year follow-up, bone mineral density testing, mortality, current disability, and living arrangements (home or institution). RESULTS: The mean age for men was 80 years vs 81 years for women. Most fractures (89% for men and 93% for women) resulted from falls from a standing height. At hospital discharge, 4.5% of men (n = 5) had treatment of any kind for osteoporosis, compared with 27% of women (n = 69) (P<.001). The 12-month mortality was 32% in men, compared with 17% in women (P =.003). Surveys were usable from 168 (87%) of 194 survivors. At 1- to 5-year follow-up, 27% (12/44) of men were taking treatment of any kind for osteoporosis, compared with 71% (88/124) of women (P<.001). Of those treated, 67% (8/12) of men and 32% (28/88) of women were taking calcium and vitamin D only. At 1- to 5-year follow-up, 11% of men had a bone mineral density measurement, compared with 27% of women. After hospital discharge, the number of men and women who required wheelchairs, walkers, and canes and who lived in institutions increased significantly. CONCLUSIONS: The burden of hip fracture is illustrated by the high incidence of postfracture disability and the high mortality rate in both men and women. Nevertheless, few men receive antiresorptive treatment.

Aged↗

Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner.

Bone is a complex highly structured mechanically active 3D tissue composed of cellular and matrix elements. The true biological environment of a bone cell is thus derived from a dynamic interaction between responsively active cells experiencing mechanical forces and a continuously changing 3D matrix architecture. To investigate this phenomenon in vitro, marrow stromal osteoblasts were cultured on 3D scaffolds under flow perfusion with different rates of flow for an extended period to permit osteoblast differentiation and significant matrix production and mineralization. With all flow conditions, mineralized matrix production was dramatically increased over statically cultured constructs with the total calcium content of the cultured scaffolds increasing with increasing flow rate. Flow perfusion induced de novo tissue modeling with the formation of pore-like structures in the scaffolds and enhanced the distribution of cells and matrix throughout the scaffolds. These results represent reporting of the long-term effects of fluid flow on primary differentiating osteoblasts and indicate that fluid flow has far-reaching effects on osteoblast differentiation and phenotypic expression in vitro. Flow perfusion culture permits the generation and study of a 3D, actively modeled, mineralized matrix and can therefore be a valuable tool for both bone biology and tissue engineering.

Alkaline Phosphatase↗