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Dive into the research topics where Darryl D. D'Lima is active.

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Featured researches published by Darryl D. D'Lima.


Journal of Bone and Joint Surgery, American Volume | 2000

The Effect of the Orientation of the Acetabular and Femoral Components on the Range of Motion of the Hip at Different Head-Neck Ratios*

Darryl D. D'Lima; Andrew G. Urquhart; Knute O. Buehler; Richard H. Walker; Clifford W. Colwell

Background: Prosthetic impingement due to poor positioning can limit the range of motion of the hip after total hip arthroplasty. In this study, a computer model was used to determine the effects of the positions of the acetabular and femoral components and of varying head-neck ratios on impingement and range of motion. Methods: A three-dimensional generic hip prosthesis with a hemispherical cup, a neck diameter of 12.25 millimeters, and a head size ranging from twenty-two to thirty-two millimeters was simulated on a computer. The maximum range of motion of the hip was measured, before the neck impinged on the liner of the cup, for acetabular abduction angles ranging from 35 to 55 degrees and acetabular and femoral anteversion ranging from 0 to 30 degrees. Stability of the hip was estimated as the maximum possible flexion coupled with 10 degrees of adduction and 10 degrees of internal rotation and also as the maximum possible extension coupled with 10 degrees of external rotation. The effects of prosthetic orientation on activities of daily living were analyzed as well. Results: Acetabular abduction angles of less than 45 degrees decreased flexion and abduction of the hip, whereas higher angles decreased adduction and rotation. Femoral and acetabular anteversion increased flexion but decreased extension. Acetabular abduction angles of between 45 and 55 degrees permitted a better overall range of motion and stability when combined with appropriate acetabular and femoral anteversion. Lower head-neck ratios decreased the range of motion that was possible without prosthetic impingement. The addition of a modular sleeve that increased the diameter of the femoral neck by two millimeters decreased the range of motion by 1.5 to 8.5 degrees, depending on the direction of motion that was studied. Conclusions: There is a complex interplay between the angles of orientation of the femoral and acetabular components. Acetabular abduction angles between 45 and 55 degrees, when combined with appropriate acetabular and femoral anteversion, resulted in a maximum overall range of motion and stability with respect to prosthetic impingement. Clinical Relevance: During total hip arthroplasty, acetabular abduction is often constrained by available bone coverage, while femoral anteversion may be dictated by the geometry of the femoral shaft. For each combination of acetabular abduction and femoral anteversion, there is an optimum range of acetabular anteversion that allows the potential for a maximum range of motion without prosthetic impingement after total hip arthroplasty. These data can be used intraoperatively to determine optimum position.


Cell Stem Cell | 2012

Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and Their Differentiated Derivatives

Kristopher L. Nazor; Gulsah Altun; Candace L. Lynch; Ha Tran; Julie V. Harness; Ileana Slavin; Ibon Garitaonandia; Franz Josef Müller; Yu Chieh Wang; Francesca S. Boscolo; Eyitayo Fakunle; Biljana Dumevska; S.J Lee; Hyun Sook Park; Tsaiwei Olee; Darryl D. D'Lima; Ruslan Semechkin; Mana M. Parast; Vasiliy Galat; Andrew L. Laslett; Uli Schmidt; Hans S. Keirstead; Jeanne F. Loring; Louise C. Laurent

Human pluripotent stem cells (hPSCs) are potential sources of cells for modeling disease and development, drug discovery, and regenerative medicine. However, it is important to identify factors that may impact the utility of hPSCs for these applications. In an unbiased analysis of 205 hPSC and 130 somatic samples, we identified hPSC-specific epigenetic and transcriptional aberrations in genes subject to X chromosome inactivation (XCI) and genomic imprinting, which were not corrected during directed differentiation. We also found that specific tissue types were distinguished by unique patterns of DNA hypomethylation, which were recapitulated by DNA demethylation during in vitro directed differentiation. Our results suggest that verification of baseline epigenetic status is critical for hPSC-based disease models in which the observed phenotype depends on proper XCI or imprinting and that tissue-specific DNA methylation patterns can be accurately modeled during directed differentiation of hPSCs, even in the presence of variations in XCI or imprinting.


Journal of Bone and Joint Surgery, American Volume | 2003

Polyethylene wear and acetabular component orientation.

Shantanu Patil; Arnie Bergula; Peter C. Chen; Clifford W. Colwell; Darryl D. D'Lima

Background: Polyethylene wear contributes substantially to both periprosthetic osteolysis and aseptic loosening after total hip arthroplasty. Acetabular component orientation has been shown to affect the range of motion of the hip as well as contact stresses. A series of studies was designed to test the hypothesis that acetabular component orientation can affect the magnitude and direction of polyethylene wear. Methods: A finite-element model was used to compute contact stresses during a normal gait cycle. Wear at the end of each gait cycle was calculated with use of the sliding-distance-coupled finite-element formulation. The wear that was calculated with use of finite-element analysis was validated by comparison with the findings of hip wear simulator studies with the acetabular liner oriented to simulate 45° and 55° of abduction. In a clinical study, fifty-six patients who underwent sixty hip arthroplasties with use of a single prosthetic design were followed for as long as five years. Radiographs were analyzed to measure the abduction angle of the acetabular component and polyethylene wear. Results: The finite-element analysis predicted increased peak contact stresses with an increased abduction angle and reduced peak contact stresses with an increased anteversion angle. Linear wear rates ranging from 0.036 to 0.045 mm/million cycles were also predicted, and increased acetabular abduction angles were predicted to be associated with higher linear wear rates. In the hip wear simulator studies, significantly different wear rates were found between the cups with acetabular abduction angles of 45° and 55° (mean, 17.2 compared with 21.7 mg/million cycles; p < 0.01). In the clinical study, radiographic analysis revealed significant correlation between the acetabular abduction angle and the linear polyethylene wear rate. A 40% increase in mean linear polyethylene wear was seen in cups with an abduction angle of ≥45°. The direction of wear was more medial (by 9.4°) in cups with an abduction angle of <45°. Conclusion: All three studies presented here underlined the importance of optimizing the position of the acetabular component. Careful attention to acetabular position may help to minimize wear.


Journal of Orthopaedic Research | 2012

Grand Challenge Competition to Predict In Vivo Knee Loads

Benjamin J. Fregly; Thor F. Besier; David G. Lloyd; Scott L. Delp; Scott A. Banks; Marcus G. Pandy; Darryl D. D'Lima

Impairment of the human neuromusculoskeletal system can lead to significant mobility limitations and decreased quality of life. Computational models that accurately represent the musculoskeletal systems of individual patients could be used to explore different treatment options and optimize clinical outcome. The most significant barrier to model‐based treatment design is validation of model‐based estimates of in vivo contact and muscle forces. This paper introduces an annual “Grand Challenge Competition to Predict In Vivo Knee Loads” based on a series of comprehensive publicly available in vivo data sets for evaluating musculoskeletal model predictions of contact and muscle forces in the knee. The data sets come from patients implanted with force‐measuring tibial prostheses. Following a historical review of musculoskeletal modeling methods used for estimating knee muscle and contact forces, we describe the first two data sets used for the first two competitions and summarize four subsequent data sets to be used for future competitions. These data sets include tibial contact force, video motion, ground reaction, muscle EMG, muscle strength, static and dynamic imaging, and implant geometry data. Competition participants create musculoskeletal models to predict tibial contact forces without having access to the corresponding in vivo measurements. These blinded predictions provide an unbiased evaluation of the capabilities and limitations of musculoskeletal modeling methods. The paper concludes with a discussion of how these unique data sets can be used by the musculoskeletal modeling research community to improve the estimation of in vivo muscle and contact forces and ultimately to help make musculoskeletal models clinically useful.


Journal of Orthopaedic Research | 2010

Decreased Knee Adduction Moment Does Not Guarantee Decreased Medial Contact Force during Gait

Jonathan P. Walter; Darryl D. D'Lima; Clifford W. Colwell; Benjamin J. Fregly

Excessive contact force is believed to contribute to the development of medial compartment knee osteoarthritis. The external knee adduction moment (KAM) has been identified as a surrogate measure for medial contact force during gait, with an abnormally large peak value being linked to increased pain and rate of disease progression. This study used in vivo gait data collected from a subject with a force‐measuring knee implant to assess whether KAM decreases accurately predict corresponding decreases in medial contact force. Changes in both quantities generated via gait modification were analyzed statistically relative to the subjects normal gait. The two gait modifications were a “medial thrust” gait involving knee medialization during stance phase and a “walking pole” gait involving use of bilateral walking poles. Reductions in the first (largest) peak of the KAM (32–33%) did not correspond to reductions in the first peak of the medial contact force. In contrast, reductions in the second peak and angular impulse of the KAM (15–47%) corresponded to reductions in the second peak and impulse of the medial contact force (12–42%). Calculated reductions in both KAM peaks were highly sensitive to rotation of the shank reference frame about the superior–inferior axis of the shank. Both peaks of medial contact force were best predicted by a combination of peak values of the external KAM and peak absolute values of the external knee flexion moment (R2 = 0.93). Future studies that evaluate the effectiveness of gait modifications for offloading the medial compartment of the knee should consider the combined effect of these two knee moments. Published by Wiley Periodicals, Inc. J Orthop Res 28:1348–1354, 2010


Arthritis Research & Therapy | 2009

Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis

Shawn P. Grogan; Shigeru Miyaki; Hiroshi Asahara; Darryl D. D'Lima; Martin Lotz

IntroductionRecent findings suggest that articular cartilage contains mesenchymal progenitor cells. The aim of this study was to examine the distribution of stem cell markers (Notch-1, Stro-1 and VCAM-1) and of molecules that modulate progenitor differentiation (Notch-1 and Sox9) in normal adult human articular cartilage and in osteoarthritis (OA) cartilage.MethodsExpression of the markers was analyzed by immunohistochemistry (IHC) and flow cytometry. Hoechst 33342 dye was used to identify and sort the cartilage side population (SP). Multilineage differentiation assays including chondrogenesis, osteogenesis and adipogenesis were performed on SP and non-SP (NSP) cells.ResultsA surprisingly high number (>45%) of cells were positive for Notch-1, Stro-1 and VCAM-1 throughout normal cartilage. Expression of these markers was higher in the superficial zone (SZ) of normal cartilage as compared to the middle zone (MZ) and deep zone (DZ). Non-fibrillated OA cartilage SZ showed reduced Notch-1 and Sox9 staining frequency, while Notch-1, Stro-1 and VCAM-1 positive cells were increased in the MZ. Most cells in OA clusters were positive for each molecule tested. The frequency of SP cells in cartilage was 0.14 ± 0.05% and no difference was found between normal and OA. SP cells displayed chondrogenic and osteogenic but not adipogenic differentiation potential.ConclusionsThese results show a surprisingly high number of cells that express putative progenitor cell markers in human cartilage. In contrast, the percentage of SP cells is much lower and within the range of expected stem cell frequency. Thus, markers such as Notch-1, Stro-1 or VCAM-1 may not be useful to identify progenitors in cartilage. Instead, their increased expression in OA cartilage implicates involvement in the abnormal cell activation and differentiation process characteristic of OA.


Journal of Orthopaedic Research | 2008

In Vivo Knee Loading Characteristics during Activities of Daily Living as Measured by an Instrumented Total Knee Replacement

Annegret Mündermann; Chris O. Dyrby; Darryl D. D'Lima; Clifford W. Colwell; Thomas P. Andriacchi

We examined the relationship between activity, peak load, medial to lateral load distribution, and flexion angle at peak load for activities of daily living. An instrumented knee prosthesis was used to measure knee joint force simultaneously with motion capture during walking, chair sit to stand and stand to sit, stair ascending and descending, squatting from a standing position, and golf swings. The maximum total compressive load at the knee was highest during stair ascending and descending and lowest during rising from a chair. Maximum total compressive load occurred at substantially different flexion angles ranging from 8.5° during walking to 91.8° during squatting. For all activities, total compressive load exceeded 2 times body weight, and for most activities 2.5 times body weight. Most activities placed a greater load on the medial compartment than the lateral compartment. Activities were grouped into three categories: high cycle loading (walk), high load (stair ascent, descent, and golf), and high flexion angle (chair sit to stand/stand to sit, and squat). The results demonstrate that the forces and motion sustained by the knee are highly activity‐dependent and that the unique loading characteristics for specific activities should be considered for the design of functional and robust total knee replacements, as well as for rehabilitation programs for patients with knee osteoarthritis or following total knee arthroplasty.


Journal of Bone and Joint Surgery, American Volume | 2005

Can Normal Knee Kinematics Be Restored with Unicompartmental Knee Replacement

Shantanu Patil; Clifford W. Colwell; Kace A. Ezzet; Darryl D. D'Lima

BACKGROUND Unicompartmental replacement can be an alternative to tibial osteotomy in younger, active patients with unicompartmental knee disease. In unicompartmental replacement, the other compartments and knee ligaments are largely untouched. Therefore, it was hypothesized that the knee kinematics after unicompartmental replacement may also be unchanged. To test this hypothesis, knee kinematics and quadriceps tension were recorded before and after replacement with a unicompartmental design and then with a tricompartmental design. METHODS Six human cadaver knees were tested before implantation, after implantation with a bicruciate-retaining unicompartmental knee prosthesis, and after implantation with a posterior cruciate-retaining tricompartmental knee prosthesis. The unicompartmental prosthesis was initially implanted, and it was then revised to a total condylar knee replacement. The knee kinematics were measured with use of an electromagnetic tracking device while the knee was put through dynamic simulated stair-climbing under peak flexion moments of approximately 40 N-m. Quadriceps tension was also measured for all three conditions. RESULTS No significant differences in tibial axial rotation were noted between the intact and unicompartmental conditions. However, tricompartmental replacement significantly affected tibial axial rotation (p = 0.001). Femoral rollback was not significantly affected by either unicompartmental or tricompartmental arthroplasty. Quadriceps tension was also similar among all three conditions. CONCLUSIONS In this in vitro cadaver study, the tricompartmental replacement significantly changed knee kinematics while the unicompartmental replacement preserved normal knee kinematics.


Recent Patents on Drug Delivery & Formulation | 2012

Thermal inkjet printing in tissue engineering and regenerative medicine.

Xiaofeng Cui; Thomas Boland; Darryl D. D'Lima; Martin Lotz

With the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the desired 2D and 3D locations, bioprinting has great potential to develop promising approaches in translational medicine and organ replacement. The most recent advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review. Bioprinting has no or little side effect to the printed mammalian cells and it can conveniently combine with gene transfection or drug delivery to the ejected living systems during the precise placement for tissue construction. With layer-by-layer assembly, 3D tissues with complex structures can be printed using scanned CT or MRI images. Vascular or nerve systems can be enabled simultaneously during the organ construction with digital control. Therefore, bioprinting is the only solution to solve this critical issue in thick and complex tissues fabrication with vascular system. Collectively, bioprinting based on thermal inkjet has great potential and broad applications in tissue engineering and regenerative medicine. This review article introduces some important patents related to bioprinting of living systems and the applications of bioprinting in tissue engineering field.


Clinical Orthopaedics and Related Research | 2001

Polyethylene contact stresses, articular congruity, and knee alignment.

Darryl D. D'Lima; Peter C. Chen; Clifford W. Colwell

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° to 90° flexion, 0 to 10 mm anteroposterior translation, 0° to 10° axial rotation, and coronal plane angulation (liftoff). Increased conformity significantly reduced contact stresses in neutral alignment (by 44% at 0° flexion and 36% at 60° and 90° 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.

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Martin Lotz

Scripps Research Institute

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Peter C. Chen

University of California

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