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Biomedical subjects

T N Gerhart

Publications and source records attributed to T N Gerhart.

At least 19 recordsLinked to original sources
PubMed1998

Healing bone using recombinant human bone morphogenetic protein 2 and copolymer.

Middiaphyseal 2.5-cm segmental defects in the right femurs of 12 sheep were stabilized with stainless steel plates and implanted with (1) 2 mg recombinant human bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)] bioerodible polymer with autologous blood (n = 7), (2) 4 mg recombinant human bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)] and blood (n = 3), or (3) poly[D,L-(lactide-co-glycolide)] and blood only (n = 2). Bone healing was evaluated for 1 year using clinical, radiographic, gross pathologic, and histologic techniques. Union occurred in three sheep in Group 1, two in Group 2, and none in Group 3. In the animals that healed, new bone first was visible radiographically between Weeks 2 and 6 after implantation; new bone mineral content equaled that of the intact femur not surgically treated by Week 16; recanalization of the medullary cavity approached completion at Week 52; and at necropsy the surgical treated femurs were rigidly healed, the poly[D,L-(lactide-co-glycolide)] was resorbed completely, and woven and lamellar bone bridged the defect site. In two Group 1 sheep euthanized at Weeks 2 and 6, polymer particles were permeated by occasional multinucleated giant cells. Some plasma cells, lymphocytes, and neutrophils were present locally. The poly[D,L-(lactide-co-glycolide)] tended to fragment during surgical implantation. Despite these observations, the recombinant human bone morphogenetic protein 2/poly[D,L-(lactide-co-glycolide)] implant was able to heal large segmental bone defects in this demanding model.

Animals↗
PubMed1998

Tibiofemoral contact pressures in degenerative joint disease.

Using tibiofemoral joints from older (age, 53-80 years) human cadavers with articular cartilage degeneration, contact pressures and contact areas were measured in the extended knee in four conditions: (1) neutral alignment; (2) 5 degrees varus (simulating single limb stance of gait); (3) 5 degrees valgus; and (4) after a 5 degrees proximal tibial closing wedge valgus osteotomy. In degenerated cartilage, contact pressures were reduced at the lesion sites and were high on the borders of the lesions. No statistically significant changes occurred in contact pressures and areas when values from neutral loading were compared with values during loading in each of the other three conditions. Lateral average and maximum contact pressures were less in varus loading than in valgus loading. Equal medial and lateral contact pressures during varus loading, in contrast to lower medial than lateral contact pressures in the other three loading, supports the theory that the varus moment imposed on the knee in single limb stance could be a mechanism causing medial tibiofemoral osteoarthritis. The 5 degrees valgus osteotomy resulted in contact pressures similar to those in neutral loading. These experiments do not support the value of the 5 degrees valgus osteotomy in reducing contact pressures on the medial tibial plateau.

Aged↗
PubMed1997

Ex vivo degradation of a poly(propylene glycol-fumarate) biodegradable particulate composite bone cement.

We have developed a biodegradable particulate composite bone cement consisting of a poly(propylene glycolfumarate)-(methylmethacrylate) matrix mixed with calcium carbonate and tricalcium phosphate particulates. Previous ex vivo studies suggest that this system provides sufficient strength for a number of potential clinical applications including structural reinforcement of osseous defects, internal fixation devices for age-related fractures, and delivery of antibiotics to treat osteomyelitis. As a first step toward investigating in vivo responses to this material, we studied the influence of varied concentrations of crosslinker, accelerator, and free radical on the mechanical properties of the cement. We then developed an ex vivo degradation assay and correlated the mechanical properties of degrading cement with the temporal changes in chemical properties of both the cement and the bathing medium. The optimal cement formulation was composed of one-third poly(propylene glycolfumarate)-(methylmethacrylate), one-third calcium carbonate, and one-third tricalcium phosphate, and provided initial compressive strengths of up to 30 MPa and compressive moduli of up to 300 MPa. Degradation rates, measured by a decline in mechanical properties, dissolution of calcium from the cement, and change in pH of the bathing medium, could be controlled by changing the concentration of reactants in the matrix. Specifically, an increase in methylmeth-acrylate or increase in both methylmethacrylate and benzoyl peroxide was inversely proportional to the rate of degradation and directly proportional to the initial mechanical properties. The degradation products and environmental changes appear to be compatible with physiologic remodeling and therefore justify examination of the in vivo response to implantation of this material.

Analysis of Variance↗
PubMed1995

Long-term healing of bone using recombinant human bone morphogenetic protein 2.

A 2.5-cm-long middiaphyseal plate-stabilized segmental defect in the right femora of 5 adult sheep was implanted with 1.5 mg of recombinant human bone morphogenetic protein 2 mixed with inactivated demineralized ovine bone matrix. Bone healing was evaluated for 12 months using clinical, radiographic, gross pathologic, and histologic techniques. Bone formation within the defect was first visible radiographically between Weeks 2 and 4 after surgery; bone union was apparent between Weeks 12 and 16, at which time the plates were removed. Recanalization of the medullary cavity with neocortex formation was near completion at Week 52. Bone mineral content at the defect sites equaled that of the nonsurgically treated intact femora by Week 16. Perifemoral soft tissue mineralization did not occur, and callus size was not greater than that formed with autograft. By Week 52, the sheep were not lame, and at necropsy the surgically treated femora were rigidly healed. Woven and lamellar bone bridged the defect site. An apparently normal sequence of ossification, modeling, and remodeling events had occurred. Recombinant human bone morphogenetic protein 2 mixed with a suitable carrier could provide an alternative to autograft for use in a variety of orthopaedic procedures.

Absorptiometry, Photon↗
PubMed1993

Antibiotic-loaded biodegradable bone cement for prophylaxis and treatment of experimental osteomyelitis in rats.

A biodegradable, particulate composite bone cement containing gentamicin and vancomycin was used for both treatment and prophylaxis of Staphylococcus aureus osteomyelitis in rats. Osteomyelitis was established by inoculating S. aureus into holes that were drilled in the proximal tibiae and were filled with polymethylmethacrylate (PMMA) cylinders. The cylinders were left in place for 3 weeks. The infections were serially evaluated by clinical and radiographic examination and by quantitative culture for colony forming units (CFUs) at the time the rats were killed. For treatment, cements containing antibiotic were implanted in animals that had established osteomyelitis and were left in place for an additional 3 weeks. Sites treated with biodegradable cement containing antibiotics exhibited significantly fewer CFUs in comparison with controls (p < 0.01). Sites treated prophylactically with the biodegradable cement developed no infections as evaluated by clinical or radiographic criteria or by quantitative culture. At this relatively early time, no significant difference in therapeutic effectiveness was found when either the biodegradable cement or PMMA was used as a carrier for antibiotics.

Animals↗
PubMed1993

Impact near the hip dominates fracture risk in elderly nursing home residents who fall.

Hip fractures among the elderly are a significant and rapidly growing public health problem. The prevailing view is that most hip fractures are the consequence of age-related bone loss or osteoporosis. However, because over 90% of hip fractures are the result of falls, we have undertaken a falls surveillance study to determine if factors related to the mechanics of falling are associated with increased risk of hip fracture. Case subjects with hip fracture and control subjects without hip fracture were sampled from falls recorded at the Hebrew Rehabilitation Center for Aged, a chronic care facility. Fall information was obtained by interview of the subject and witnesses if the fall was witnessed. Data were analyzed by multiple logistic regression. Increased risk of hip fracture from a fall was associated with impacting on the hip or side of the leg and potential energy associated with the fall. Quetelet, or body mass index, was inversely related to fracture risk. The adjusted odds ratio of hip fracture for a fall involving impact on the hip region was 21.7 (95% confidence interval, 8.2-58). The potential energy associated with these falls was an order of magnitude greater than the average energy required to fracture elderly, cadaveric, proximal femurs in earlier in vitro experiments. We conclude, therefore, that a fall from standing height should no longer be considered minimal trauma but rather trauma of sufficient magnitude to pose a high risk of hip fracture if impact occurs on the hip and if energy-absorbing processes are inadequate.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidental Falls↗
PubMed1993

Healing segmental femoral defects in sheep using recombinant human bone morphogenetic protein.

A middiaphyseal, 2.5-cm osteoperiosteal segmental defect stabilized by plate fixation was created in the right femur of 17 sheep. Four treatment groups were included: Group I, no implant; Group II, inactive bone matrix; Group III, recombinant human bone morphogenetic protein (rhBMP-2) mixed with inactive bone matrix; and Group IV, autogeneic bone graft. Three animals had early failure of fixation, and the remaining 14 were evaluated at three months after implantation. Radiographs showed bony union of all defects treated with rhBMP-2 (six) and a lack of bony union in the negative-control groups treated with no implant (three) and inactive bone matrix without BMP (three). Both defects treated with autograft healed. New bone formation in the defect sites treated with rhBMP-2 first appeared one month after implantation and had a mean bending strength (expressed as a percentage of the contralateral femur) of 91% +/- 59% (mean +/- standard deviation) for defects treated with BMP-2, 77% +/- 34% for autograft, 9% +/- 8% for no implant, and 11% +/- 7% for inactive matrix without BMP. Three sheep treated with rhBMP-2 had their fixation plates removed at four months and were followed for one year. Their bone defect sites remained solidly healed one year after the initial operation.

Animals↗
PubMed1992

Holding power and reinforcement of cancellous screws in human bone.

The authors report an in vitro biomechanical evaluation of a biodegradable material that might be used for the reinforcement of surgical screws in fractures involving severely osteoporotic bone. The material is a particulate composite with a matrix phase consisting of a hydrolyzable prepolymer, polypropylene fumarate (PPF), crosslinked with methacrylate monomer, and a particulate phase consisting of tricalcium phosphate and calcium carbonate. Pullout force and stripping load of cancellous screws were determined along with screw pullout force before and after reinforcement with either polymethylmethacrylate (PMMA) or PPF composite. Pullout force was moderately correlated (R2 = 0.59) with apparent density by a power law relationship of the form 0.065p1.37-1.77. Stripping load was strongly correlated (R2 = 0.91) with apparent density by a power law of the form 0.13p1.35-93.8. Mean pullout force before and after reinforcement with PMMA was 382 +/- 100 N (mean +/- standard deviation) and 879 +/- 315 N, respectively. Mean pullout force before and after reinforcement with PPF composite was 571 +/- 294 N and 829 +/- 354 N, respectively. Although the increase in pullout force with cement reinforcement was highly significant in both cases, the magnitude of the increase did not depend on the type of cement. Thus PPF seems to provide reinforcement that is equivalent to that provided by PMMA.

Aged↗
PubMed1992

Failure of growth hormone to alter the biomechanics of fracture-healing in a rabbit model.

Standardized tibial osteotomies were created and stabilized with external fixation in twenty-seven skeletally mature rabbits. Fourteen animals were treated with a daily injection of human growth hormone (150 micrograms per kilogram of body weight), and thirteen received a daily injection of saline solution. Serial non-destructive biomechanical tests, radiography, and determinations of the levels of serum insulin-like growth-factor I were performed for all of the animals. Destructive strength-testing of the sites of osteotomy was performed at four, six, or eight weeks. Twenty-five of the twenty-seven osteotomies healed uneventfully. There were no significant differences in the serial biomechanical measurements at the sites of the healing osteotomies, in the radiographic measurements, or in the ultimate strength of the sites of the osteotomy between the two groups. The mean level of serum insulin-like growth-factor I increased 33 per cent relative to the preoperative baseline level in the group that received growth hormone and increased 10 per cent in the control group. This difference was not statistically significant. There was no significant correlation between the biomechanical properties at the sites of the osteotomies and the levels of serum insulin-like growth-factor I. Administration of growth hormone had no measurable effect on fracture-healing in this model of normal animals. It remains to be determined whether injection of growth hormone might affect healing when there is a state of deficiency of endogenous growth hormone or when there is a non-union of a fracture.

Analysis of Variance↗
PubMed1991

Biomechanical evaluation of a biodegradable composite as an adjunct to internal fixation of proximal femur fractures.

Internal fixation of comminuted unstable fractures of the severely osteoporotic proximal femur is sometimes supplemented with polymethyl-methacrylate (PMMA). We here report an in vitro biomechanical evaluation of a biodegradable particulate composite that might be used for similar purposes. The composite includes a matrix phase consisting of a hydrolyzable prepolymer [polypropylene fumarate (PPF)] cross-linked with methacrylate monomer, and a particulate phase consisting of tricalcium phosphate and calcium carbonate. We implanted dynamic hip screws in 22 cadaveric proximal femora and measured the yield load for an oblique force applied to the femoral head. The hip screws were then reinforced with either PMMA or the PPF composite and tested again. On the basis of analysis of variance, the average increases in yield load for PMMA and PPF reinforcement of 1,750 and 1,130 N were statistically significant (p less than 0.00005), suggesting that both materials enhance congruence between implant and bone and thereby increase the projected load-bearing area of the implant. The increase in yield force with PMMA was slightly higher than the increase with PPF (p less than 0.05), but both values after reinforcement were close (3,790 +/- 561 N for PMMA vs. 3,240 +/- 669 N for PPF). If we can demonstrate that appropriate rates of degradation, bony ingrowth, and static and fatigue properties can be achieved in vivo with this system, our data suggest that this PPF composite may have potential as an adjunct to the internal fixation of unstable fractures of the osteoporotic hip.

Aged↗
PubMed1991

Mechanical properties of metaphyseal bone in the proximal femur.

We used a three-point bending test to investigate the structural behavior of 123 rectangular flat plate specimens harvested from the metaphyseal shell of the cervical and intertrochanteric regions of five fresh/frozen human proximal femora. For comparison purposes, 36 specimens of similar geometry were also fabricated from bone of the femoral diaphysis. All specimens were oriented in either the local longitudinal or transverse directions. The mean longitudinal elastic modulus was 9650 +/- 2410 (SD) MPa and demonstrated a 24% decrease from that measured for the diaphysis (12500 +/- 2140 MPa) using the same testing technique. However, the transverse elastic moduli did not differ significantly between the proximal (5470 +/- 1720 MPa) and diaphyseal (5990 +/- 1520 MPa) specimens. The globally averaged values for the ultimate tensile strengths of the metaphyseal shell were 101 +/- 26 MPa in the longitudinal and 50 +/- 12 MPa in the transverse directions. These compared with diaphyseal values of 128 +/- 16 MPa and 47 +/- 12 MPa, respectively. While these differences were largely due to the reduced density of the proximal specimens, a slight decrease in transverse anisotropy for the proximal specimens was also noted by comparing the ratio of longitudinal to transverse moduli (1.76) and tensile strength (2.02) to the diaphyseal values (2.09 and 2.71, respectively). Use of these data should lead to improved performance of analytical models for the proximal femur, and thus help focus increased attention on the structural contribution of trabecular bone to the strength and rigidity of the proximal femur.

Acrylic Resins↗
PubMed1991

Low-molecular-weight heparinoid compared with warfarin for prophylaxis of deep-vein thrombosis in patients who are operated on for fracture of the hip. A prospective, randomized trial.

In a randomized, prospective trial, a low-molecular-weight heparinoid (Org 10172 [Lomoparan]) was compared with warfarin for efficacy and safety in preventing deep-vein thrombosis in 263 patients who had an operatively treated fracture of the hip. One group of patients received Org 10172 in a dose of 750 units subcutaneously every twelve hours until the ninth postoperative day; on the seventh postoperative day, warfarin was added to the regimen. The other group received only warfarin. Both drugs were begun preoperatively, immediately after the admission evaluation. In the patients who received warfarin, the desired prothrombin time was one and one-half times the control level. Deep-vein thrombosis was detected by 125I-fibrinogen scanning and impedance plethysmography and was confirmed by phlebography and compression ultrasonography. Deep-vein thrombosis was found in nine (7 per cent) of the 132 patients who received Org 10172 and in twenty-eight (21 per cent) of the 131 patients who received warfarin (p less than 0.001). Adverse reactions were not significantly different in the two groups. Major bleeding complications occurred in eight patients in the Org-10172 group, only four of whom were receiving the drug at the time of bleeding, and in five patients who were receiving warfarin (not significant). There was no difference in intraoperative loss of blood or in requirements for transfusion. We concluded that the low-molecular-weight heparinoid Org 10172 is a safe, convenient, effective antithrombotic agent for the prevention of venous thrombosis after an operation for fracture of the hip.

Aged↗
PubMed1989

In vivo histologic and biomechanical characterization of a biodegradable particulate composite bone cement.

A biodegradable particulate composite bone cement consisting of a crosslinked gelatin matrix and tricalcium phosphate particles was implanted intraosseously in rabbits for up to 12 weeks. Cured cylindrical implants were inserted in holes drilled in the proximal tibial metaphysis. Sequential fluorochrome labeling and radiographs were done, and specimens were processed for decalcified and nondecalcified histology. At 4 weeks, the cross-sectional diameter of the implant was slightly greater than at implantation. There was considerable dissolution of the matrix and some new bone ingrowth. At 12 weeks, the diameter was reduced to half the original diameter and bone had grown throughout the matrix. In the distal femur, freshly mixed cement was used to stabilize an osteochondral fracture. Mechanical testing of the cement-stabilized fracture revealed a decrease in compressive strength and modulus at 4 weeks followed by an increase to greater than initial values at 12 weeks. Over time, the osteochondral fragment subsided into the underlying cement, but the subsidence did not correlate with mechanical strength. This osteochondral fracture model permits measurement of the overall material properties of a cement simultaneously weakened by resorption and reinforced by ingrowing bone.

Animals↗
PubMed1988

In vitro characterization and biomechanical optimization of a biodegradable particulate composite bone cement.

We have developed a biodegradable particulate composite bone cement and used in vitro and in vivo methods for studying its suitability for orthopaedic applications. The composite matrix consists of gelatin, water, and sodium salicylate. The particulate phase is made up of powdered and particulate (355-600 microns diameter) tricalcium phosphate. Paraformaldehyde (0.1% to 0.5% by weight) is used as a matrix cross-linking agent. The effects of incubation time, particulate volume fraction, density of the individual particles, water content, concentration of crosslinking agent, and freeze-drying on the unconfined compressive strength and modulus of the particulate composite were measured. Compressive strengths of 7 MPa and moduli of 65 MPa could be achieved. Mechanical properties depended critically upon the water content of the particulate composite, with values of strength and modulus decreasing rapidly outside a range of 10-14% of specimen dry weight. High-density tricalcium phosphate particulate produced cement with twice the strength found with porous particulate. In a companion study we document in vivo performance of this particulate composite in an animal model system.

Biocompatible Materials↗
PubMed1988

Antibiotic release from an experimental biodegradable bone cement.

An experimental biodegradable bone cement [poly(propylene fumarate)-methylmethacrylate] (PPF-MMA) has been compared in vivo with polymethylmethacrylate (PMMA) as a carrier agent for local release of antibiotics. This approach is potentially applicable to the treatment of chronic osteomyelitis where the clinical goal is to achieve sustained high concentrations of antibiotics locally in the infected bone. In our experiments, gentamicin- and vancomycin-impregnated cylindrical PMMA and PPF-MMA cement specimens were implanted subcutaneously in rats, and blood and wound fluid samples were obtained over a 2-week period. Antibiotic levels were determined using immunoassays, and microbiologic activity was confirmed with agar diffusion techniques. The biodegradable PPF-MMA cement achieved and maintained considerably higher wound antibiotic levels than did PMMA cement. Vancomycin levels for the PPF-MMA cement were greater than 20 times those for the PMMA cement at all sampling times from 24 h to 14 days. For both cements, the serum antibiotic concentrations remained safely below maximum levels recommended for parenteral therapy. Mechanical testing of the PPF-MMA cement showed that admixture of 3% by weight of antibiotic did not adversely affect material properties. We conclude that this experimental biodegradable bone cement (PPF-MMA) can be used as a carrier to achieve high sustained local levels and low serum levels of antibiotics. Because it is biodegradable and thus does not require a secondary procedure for removal, it has special potential for use in treatment of chronic osteomyelitis.

Administration, Topical↗
PubMed1986

Biomechanical optimization of a model particulate composite for orthopaedic applications.

Particulate composites are a potential solution to the need for an injectable, biocompatible, resorbable material that could be used to reinforce fractures and defects in bone and temporarily to stabilize porous ingrowth prostheses. We have developed a model system for producing and testing particulate composites to determine if mechanical properties suitable for orthopaedic applications can be achieved. The experiments used bovine cortical bone and various forms of hydroxyapatite for the particulate phase and a collagen and particulate reinforce gelatin-resorcinol-formaldehyde (G-R-F) adhesive for the matrix phase. Using unconfined compression testing, we measured the effects of variation in particulate type, size, shape, and volume fraction on the material properties of the particulate composites. We found that compressive strengths greater than 10 MPa and compressive moduli greater than 100 MPa could be achieved in this model system. Rough and irregular particulates exhibited higher compressive strengths and moduli than smooth and spherical particulates. Mechanical properties were largely independent of particulate size in the range of 125-850 microns diameter. This model system suggests that, with the development of new biocompatible matrix materials, particulate composites with mechanical properties suitable for orthopaedic applications can be achieved.

Animals↗
PubMed1986

Compartmental pressure monitoring after arterial reconstruction lacks clinical relevance.

Anterior compartmental intramuscular pressure was studied by the continuous-infusion technique during and after arterial reconstruction of the abdominal or lower extremity vessels in 23 patients. Although there were significant differences between the mean pressures in those patients who had proximal or distal arterial reconstruction, the mean pressure did not increase in the sequential preocclusion, occlusion, and postoperative periods during a mean follow-up of 26 hours in proximal reconstructions and 19 hours in distal reconstructions. One patient had pressures consistent with a borderline compartmental syndrome but died of a ruptured left ventricle before complete correlation of the clinical course and pressures could be made. We conclude from this study that although routine measurement of compartmental pressures during arterial reconstruction of the lower extremities yields interesting findings, it makes no important contribution to the clinical management of the patient.

Blood Pressure↗