Biomedical subjects
D D D'Lima
Publications and source records attributed to D D D'Lima.
Human chondrocyte apoptosis in response to mechanical injury.
OBJECTIVE: The effect of mechanical injury on chondrocyte viability and matrix degradation was studied. It was proposed that mechanical injury to human cartilage explants results in chondrocyte apoptosis with associated loss of glycosaminoglycans. DESIGN: Full thickness human cartilage explants, 5 mm in diameter were subjected to a single static mechanical stress of 14 MPa for 500 ms under radially unconfined compression. Glycosaminoglycan (GAG) release and percentage of cells undergoing apoptosis were measured at 96 h after injury. To establish the time course of apoptosis, explants were subjected to 30% strain and cultured for varying intervals up to 7 days after injury. A group of loaded explants were also treated with the broad spectrum caspase inhibitor z-Vad.fmk after injury. RESULTS: Internucleosomal DNA fragmentation as one indicator of apoptosis was observed in 34% (S.D.+/-11) of chondrocytes at 96 h in response to mechanical loading at 14 MPa, compared to 4% (S.D.+/-2) in the non-loaded explants. Evidence for cell death induction via apoptosis was also obtained by electron microscopy and caspase cleavage of cytokeratin. GAG release was also higher for the loaded explants, mean 1.9% (S.D.+/-0.14) of total GAG content, compared to control explants, mean 0.8% (S.D.+/-0.28). The percentage of apoptotic cells also correlated with the level of GAG release into the culture media. The percentage of apoptotic chondrocytes demonstrated a progressive increase from 6 h to 7 days post-injury. When loaded explants were cultured in z-Vad.fmk after injury, a 50% reduction in apoptosis rates was seen. CONCLUSIONS: These results demonstrate that mechanical injury induces chondrocyte apoptosis and release of GAG from the matrix. The time course suggests that a therapeutic window may exist where apoptosis could be inhibited. This potentially identifies a new approach to chondroprotection.
Patellar tracking in total knee arthroplasty: inset versus onset design.
Patellar components come in onset and inset designs. Kinematic differences between these designs were studied in a cadaver model of closed kinetic chain knee extension. Seven frozen knees were implanted with a standard posterior cruciate-retaining design. Each knee first was tested with the inset design, followed by the onset design in the Oxford Knee Rig. Three-dimensional tracking of the femur, tibia, and patella was performed using an electromagnetic system during active knee extension under load. No statistically significant differences were seen in knee kinematics between the 2 designs. The inset patella tended to shift laterally and tilt laterally more than the onset patella. This difference may be clinically significant.
Tibiofemoral conformity and kinematics of rotating-bearing knee prostheses.
Increasing tibiofemoral articular conformity theoretically increases articular contact area and reduces contact stresses in total knee arthroplasty. Fixed-bearing knee designs possess relatively low tibiofemoral conformity, in part to allow tibiofemoral rotation without generating excessive stresses at the articulation or the implant-bone interface. This study analyzed knee kinematics of mobile-bearing designs in a closed chain dynamic knee extension model in posterior cruciate-retaining design with high- and low tibiofemoral conformity and posterior cruciate-substituting designs with and without rotational constraint. Overall, for all conditions, the mobile-bearing insert rotated with the femur in the presence of tibiofemoral axial rotation. In addition, the correlation of bearing rotation with femoral rotation was stronger for the high-conformity and rotationally-constrained designs than for the low-conformity designs and strongest for the posterior cruciate-retaining high-conformity condition. Changes in conformity or rotational constraint did not appear to affect femoral roll back, tibiofemoral axial rotation, or varus-valgus angulation. The results suggest that mobile-bearing inserts rotate with the femur and increasing conformity or rotational constraint in mobile-bearing design knee prostheses does not affect knee kinematics adversely, at least under closed chain knee extension conditions in vitro.
Impact of mechanical trauma on matrix and cells.
Posttraumatic arthritis is one of the most common causes of secondary osteoarthritis. The contribution of cell death to matrix degradation has not been characterized fully. The current study was designed to determine the effect of mechanical injury on chondrocyte viability and matrix degradation. Full-thickness bovine and human cartilage explants, 5 mm in diameter were subjected to mechanical loads representative of traumatic joint injury. Glycosaminoglycan release and percent apoptotic cells were measured. Unilateral patellas in eight anesthetized rabbits were subjected to an impact load. Rabbits were euthanized at 96 hours after injury and patellar cartilage was harvested for analysis. The effect of a pan-caspase inhibitor, z-VAD.fmk [benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone] in preventing chondrocyte apoptosis in human articular cartilage explants was determined. A significant increase in the number of apoptotic cells was observed in response to mechanical loading. The mean in vivo apoptotic rates were 1% in control rabbits and 15% in impacted patellas. Caspase inhibition reduced chondrocyte apoptosis from 34% to 25% after mechanical injury and was associated with reduction in glycosaminoglycan release. Mechanical injury induces chondrocyte apoptosis that is sensitive to pharmacologic inhibition. This identifies a new approach to limit traumatic cartilage injury and the subsequent development of secondary osteoarthritis.
In vivo changes after mechanical injury.
Chondrocytes undergo apoptosis in response to mechanical injury in vitro. The current clinical study correlates arthroscopic and magnetic resonance imaging results with biopsy specimens of cartilage from patients with knee injury. Twenty patients were evaluated at a mean 2.7 months after acute knee injury. The mean age of the patients was 32 years and the mean weight was 83 kg. Cartilage lesions were graded separately on magnetic resonance images and arthroscopy in a blinded manner. During arthroscopy, a 1.8 mm diameter biopsy specimen was obtained from the edge of cartilage lesion. The biopsy specimen underwent histologic examination by safranin O staining and detection of chondrocyte apoptosis by the presence of deoxyribonucleic acid fragmentation. There was a positive correlation in 50% (10 of 20) when the presence or absence of cartilage lesions by magnetic resonance imaging was correlated with arthroscopy. All cases of partial thickness or full-thickness cartilage loss that were seen by arthroscopy also were detected by magnetic resonance images. Apoptotic cells were significantly more numerous in biopsy specimens from lesions compared with control biopsy specimens. The findings of reduced cell viability attributable to apoptosis may have profound implications for cartilage repair. This opens potential therapeutic avenues for the treatment of posttraumatic cartilage lesions through apoptosis prevention.
Clinical objectives for cartilage repair.
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Polyethylene wear and variations in knee kinematics.
A six-station knee wear simulator was used to test a posterior cruciate-retaining total knee arthroplasty design. Six implants each were tested in three groups; low intensity, high intensity, and malalignment using kinematic inputs from normal gait data, more severe loading conditions, and 3 degrees varus malalignment, respectively. For each group, gravimetric wear of the polyethylene inserts was measured for 5,000,000 cycles. Knee wear testing showed significantly different results for the three groups. Low intensity group inserts had mean wear rates of 3.1 (+/- 1.2) mg per million cycles. High intensity group inserts had significantly higher mean wear rates of 7.4 (+/- 2.7) mg per million cycles. Malalignment group inserts had the highest wear rates of 9.2 (+/- 3.3) mg per million cycles. The wear generated in the knee simulator seems to be dependent on the relative motions and loads at the articulating surface. The high intensity groups were subjected to motions that included reciprocating anteroposterior translations and a higher peak axial load than the low intensity group. This resulted in increasing the amount of wear. Varus malalignment also increased the total wear significantly. These results may explain some of the wide variations in wear seen in retrieved knee implants.
Quadriceps moment arm and quadriceps forces after total knee arthroplasty.
Knee prosthetic designs that increase quadriceps moment arm can reduce quadriceps tension and patellofemoral compressive forces. Six knees from cadavers were tested on the Oxford knee rig, which simulates closed chain knee extension under load. Three conditions were tested sequentially for each knee: Normal, Control (implanted with the Osteonics 7000 knee design), and Scorpio (implanted with the Osteonics Scorpio design). The center of flexion-extension of the Scorpio design was 10 mm posterior to that of Control that served to lengthen the quadriceps moment arm. An electromagnetic tracking system measured dynamic knee kinematics, and a uniaxial load cell measured quadriceps tension. The Scorpio design reduced quadriceps tension when compared with the Normal or Control knee ranging from 5% to 20%. This was statistically significant at flexion angles greater than 50 degrees. In three knees, the patellar component was instrumented with a triaxial load cell that measured patellofemoral forces. Patellofemoral forces were lower with the Scorpio design compared with the Control. Increasing quadriceps lever arm reduces quadriceps forces and can facilitate activities of daily living and enhance patient rehabilitation. Reduced quadriceps forces may result in reduced patellofemoral forces that can have a beneficial effect on anterior knee pain, patellar component wear, and loosening.
Polyethylene contact stresses, articular congruity, and knee alignment.
Increased conformity at the tibiofemoral articulation increases contact area and reduces contact stresses in total knee arthroplasty. Malalignment, however, can increase polyethylene contact stresses. The effect of knee alignment and articular conformity on contact stresses was evaluated in a finite element model. The polyethylene insert and femoral component were modeled in high- and low-conformity conditions. An axial tibial load of 3000 N was applied across the tibiofemoral articulation at different knee positions ranging from 0 degrees, to 90 degrees, flexion, 0 to 10 mm anteroposterior translation, 0 degrees to 10 degrees axial rotation, and coronal plane angulation (liftoff). Increased conformity significantly reduced contact stresses in neutral alignment (by 44% at 0 degrees flexion and 36% at 60 degrees and 90 degrees flexion). Liftoff significantly increased contact stresses in low- and high-conformity conditions, but to a lesser degree in the high-conformity condition. Malalignment in rotation was most detrimental especially with the high-conformity insert design. Overall, increasing articular conformity reduced stresses when the knee was well-aligned. However, malalignment in axial rotation was detrimental. Mobile-bearing knee designs with increased articular congruity may result in lower contact stresses, especially the rotating-bearing designs that theoretically minimize rotational malalignment.
Cartilage injury induces chondrocyte apoptosis.
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In vitro and in vivo models of cartilage injury.
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Prevention of chondrocyte apoptosis.
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e-Knee: evolution of the electronic knee prosthesis. Telemetry technology development.
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Optimizing acetabular component position to minimize impingement and reduce contact stress.
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What's new in orthopaedic rehabilitation.
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The Harris-Galante Porous acetabular component at intermediate follow-up.
Outcome of the acetabular component in 90 consecutive primary noncemented total hip arthroplasties (THAs) was prospectively studied. The acetabular cup consisted of a hemispherical titanium alloy shell with a titanium fiber-mesh porous coating and a modular polyethylene liner (Harris-Galante Porous-1, Zimmer, Warsaw, Ind). The cup was implanted using line-to-line reaming with adjunctive dome screw fixation. The femoral component consisted of a titanium alloy stem with titanium fiber-mesh porous coating and a 28-mm cobalt-chrome modular head. Mean patient age was 53 years (range: 27-75 years); male:female ratio was 48:42; and mean follow-up was 6 years (range: 4.5-8 years). One acetabular component was revised for aseptic loosening. Of 81 unrevised hips available for follow-up, mean Harris hip score was 57 preoperatively and 96 at final follow-up (72% excellent, 15% good, 1 3% fair, and none poor). Of 61 unrevised hips with adequate radiographic follow-up, radiographic failure (complete periprosthetic radiolucency) was evident in 3 (4.9%) and periacetabular osteolysis in none. Radiographic failure did not correlate with poor clinical outcome. Linear polyethylene wear rate (mean: 0.13 mm/year) did not correlate with age, gender, weight, outcome, or cup abduction angle, but did correlate with the presence of femoral periprosthetic osteolysis (0.18 mm/year with femoral osteolysis versus 0.11 mm/year without; P= .01). This series of porous-coated hemispherical cups demonstrated excellent intermediate-term clinical and radiographic outcome, comparable with similarly favorable results reported by the prosthesis designers. A potentially adverse effect of polyethylene wear on the longevity of a THA was supported by a positive correlation between polyethylene wear rate and femoral osteolysis.
Indomethacin versus radiation therapy for heterotopic ossification after hip arthroplasty.
This study compared the efficacy and cost of radiation therapy with indomethacin in the prophylaxis of heterotopic ossification following total hip replacement. Twenty-two patients received a radiation dose of 10 Gy in five fractions, 28 patients 8 Gy in one fraction, and 27 patients 25 mg oral indomethacin three times a day for either 7 or 21 days. Patients at higher risk for heterotopic ossification were more likely to receive radiation therapy than indomethacin. At a mean follow-up of 2 years, there were no differences in failure rates between the high-risk patients treated with radiation and the low-risk patients treated with indomethacin. Currently, the patient-billed cost of radiation is $1400 whereas the cost for indomethacin is approximately $100. Indomethacin appears to be as effective as radiation therapy in patients at low to moderate risk for heterotopic ossification and offers significant cost savings.