Effect of Passaging on Bovine Chondrocyte Gene Expression and Engineered Cartilage Production.

Tissue engineering strategies show great potential for repairing osteochondral defects in osteoarthritic joints; however, these approaches often rely on passaging cells multiple times to obtain enough cells to produce functional tissue. Unfortunately, monolayer expansion culture causes chondrocyte dedifferentiation, which is accompanied by a phenotypical and morphological shift in chondrocyte properties that leads to a reduction in the quality of de novo cartilage produced. Thus, the objective of this study was to evaluate transcriptional variations during in vitro expansion culture and determine how differences in cell phenotype from monolayer expansion alter development of functional engineered cartilage. We used an unbiased approach to explore genome-wide transcriptional differences in chondrocyte phenotype at passage 1 (P1), P3, and P5, and then seeded cells into hydrogel scaffolds at P3 and P5 to assess cells' abilities to produce cartilaginous extracellular matrix in three dimensional (3D). We identified distinct phenotypic differences, specifically for genes related to extracellular organization and cartilage development. Both P3 and P5 chondrocytes were able to produce chondrogenic tissue in 3D, with P3 cells producing matrix with greater compressive properties and P5 cells secreting matrix with higher glycosaminoglycan/DNA and collagen/DNA ratios. Furthermore, we identified 24 genes that were differentially expressed with passaging and enriched in human osteoarthritis (OA) genome-wide association studies, thereby prioritizing them as functionally relevant targets to improve protocols that recapitulate functional healthy cartilage with cells from adult donors. Specifically, we identified novel genes, such as TMEM190 and RAB11FIP4, which were enriched with human hip OA and may play a role in chondrocyte dedifferentiation. This work lays the foundation for several pathways and genes that could be modulated to enhance the efficacy for chondrocyte culture for tissue regeneration, which could have transformative impacts for cell-based cartilage repair strategies.

Priming chondrocytes during expansion alters cell behavior and improves matrix production in 3D culture.

OBJECTIVE: Cartilage tissue engineering strategies that use autologous chondrocytes require in vitro expansion of cells to obtain enough cells to produce functional engineered tissue. However, chondrocytes dedifferentiate during expansion culture, limiting their ability to produce chondrogenic tissue and their utility for cell-based cartilage repair strategies. The current study identified conditions that favor cartilage production and the mechanobiological mechanisms responsible for these benefits. DESIGN: Chondrocytes were isolated from juvenile bovine knee joints and cultured with (primed) or without (unprimed) a growth factor cocktail. Gene expression, cell morphology, cell adhesion, cytoskeletal protein distribution, and cell mechanics were assessed. Following passage 5, cells were embedded into agarose hydrogels to evaluate functional properties of engineered cartilage. RESULTS: Priming cells during expansion culture altered cell phenotype and chondrogenic tissue production. Unbiased ribonucleic acid-sequencing analysis suggested, and experimental studies confirmed, that growth factor priming delays dedifferentiation associated changes in cell adhesion and cytoskeletal organization. Priming also overrode mechanobiological pathways to prevent chondrocytes from remodeling their cytoskeleton to accommodate the stiff, monolayer microenvironment. Passage 1 primed cells deformed less and had lower yes associated protein 1 activity than unprimed cells. Differences in cell adhesion, morphology, and cell mechanics between primed and unprimed cells were mitigated by passage 5. CONCLUSIONS: Priming suppresses mechanobiologic cytoskeletal remodeling to prevent chondrocyte dedifferentiation, resulting in more cartilage-like tissue-engineered constructs.

Patient-Reported Outcomes of Kinematic vs Mechanical Alignment in Total Knee Arthroplasty: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Background: Total knee arthroplasty (TKA) is an effective treatment method for severe osteoarthritis of the knee. Poor alignment of a knee replacement has been associated with suboptimal clinical results. Traditionally, mechanical alignment (MA) has been considered the gold standard. In light of reports of decreased satisfaction with TKA, a new technique called kinematic alignment (KA) has been developed. The purpose of this study is to (1) review the results of KA and MA for TKA in randomized controlled trials based on the Western Ontario and McMaster Universities Arthritis Index score, the Oxford Knee Score, and the Knee Society Scores, (2) perform a meta-analyses of the randomized controlled trials with baseline and follow-up values of these parameters, and (3) discuss other shortcomings of this literature from the perspective of study design and execution. Methods: Two independent reviewers performed a systematic review of the English literature using the Embase, Scopus, and PubMed databases searching for randomized controlled trials of MA vs KA in TKA. Of the initial 481 published reports, 6 studies were included in the final review for meta-analysis. The individual studies were then analyzed to evaluate for risks of bias and inconsistencies of methodology. Results: A majority of studies demonstrated low risk of bias. All studies had fundamental technical issues by utilizing different techniques to achieve KA vs MA. There was no significant difference between KA and MA in these studies. Conclusions: There is no significant difference in any outcomes measured between KA and MA in TKA. Both statistical and methodological factors diminish the value of these conclusions.

Improving Technical Outcome in Osteochondral Allograft Transplantation of the Femoral Trochlea: The Role of Contoured Guides, Experience Level, Graft Size, and Graft Position.

Background: The use of coring instrumentation for osteochondral allograft (OCA) transplantation of the femoral trochlea is challenging due to the complex topography of this anatomical area. Purpose: We sought to determine the effect of flat guides versus guides contoured to the surface of the trochlea on graft step-off in trochlear OCAs performed on a foam bone model. We also determined the effect of surgeon experience level and graft size on step-off. Study Design: Controlled laboratory study. Methods: Allograft harvesters were produced in 3 different sequential sizes with either a flat or a contoured undersurface. The guides matched one another in all aspects of shape and size except for the undersurface contour. The contoured undersurface generally matched the surface of the bone model trochlea but was not customized to that surface. A total of 72 foam femora were obtained. Identical trochlear stellate lesions of 3 different sizes (small, medium, and large) were created using 3-dimensional printed surface templates. A total of 6 surgeons (3 attending and 3 resident surgeons) performed OCAs of each trochlear lesion. Each surgeon performed 1 graft for each size and each guide type (n = 6 per surgeon). A specialized digital caliper was prepared that allowed the measurement of graft step-off to within 0.01 mm at a distance of 5 mm between the 2 sensors. The measurements were performed at 8 positions around the clockface of the grafts. Results: Grafts performed with the contoured guides had a mean step-off of 0.43 ± 0.37 mm. Grafts performed with the flat guides had a mean step-off of 0.74 ± 0.78 mm (P < .0001). Experience level did not have a significant effect on graft step-off (P = .81). There was no identifiable pattern indicating higher step-off at any one position on the clockface. Conclusion: In this study, contoured grafts had significantly lower step-offs compared with flat guides. Experience level, clockface position, and graft size did not affect step-off.

Acetabular cartilage repair: state of the art in surgical treatment.

Hip preservation has emerged as a developing surgical subspecialty with a variety of tools to address hip joint pain and dysfunction. Cartilage tears and delamination are caused by injury to the hip and can ultimately progress to osteoarthritis. It has been established that the acetabulum is particularly at risk of cartilage injury secondary to trauma, hip dysplasia and hip impingement. In spite of the high frequency of acetabular cartilage lesions based on our experience and the literature, there is no consensus as to the optimal treatment of these lesions. This review article highlights the challenges in treating cartilage injuries of the acetabulum with a particular emphasis on published studies and technical considerations in performing these procedures.

Extensive Recontouring of the Femoral Head with Osteochondral Allografting: A Case Report with Histological and MicroCT Analysis.

Morphological abnormalities such as cam deformity or growth disturbances can have a detrimental effect on the smooth function of the hip joint. This case reports an attempt to salvage the hip joint of a young patient with a posttraumatic growth disturbance of the femoral head using a fresh osteochondral allograft. This treatment has been used very rarely in the femoral head due to the presumed tenuous blood supply of the head and the perceived risk of nonunion or progressive avascular necrosis. The patient in this case had persistent pain and mechanical symptoms leading to hip replacement. A detailed analysis of the retrieved femoral head demonstrated durability and healing of the grafts based on gross inspection, histology of bone and cartilage, and microCT analysis. This case is the first report to our knowledge of a detailed histological and radiographic analysis of the fate of osteochondral allografts of the femoral head. We hope that this case provides justification for the use of osteochondral allografts of the femoral head for other indications such as femoral head fractures, avascular necrosis, and benign epiphyseal tumors of the femoral head in an effort to avoid arthroplasty in young patients. The authors have obtained the patient's informed written consent for print and electronic publication of the case report.

Do small changes in rotation affect measurements of lower extremity limb alignment?

BACKGROUND: The alignment of the lower extremity has important implications in the development of knee arthritis. The effect of incremental rotations of the limb on common parameters of alignment has not been studied. The purpose of the study was to (1) determine the standardized neutral position measurements of alignment and (2) determine the effect of rotation on commonly used measurements of alignment. METHODS: Eighty-seven full length CT angiography studies (49 males and 38 females, average age 66 years old) were included. Three-dimensional models were created using a rendering software program and placed on a virtual plane. An image of the extremity was obtained. Thirty scans were randomly selected, and those models were rotated in 3° intervals around the longitudinal axis and additional images were obtained. RESULTS: In the neutral position, the mechanical lateral distal femoral articular angle (mLDFA) was 85.6 ± 2.3°, medial proximal tibial angle (MPTA) was 86.1 ± 2.8°, and mechanical tibiofemoral angle (mTFA) was -0.7 ± 3.1°. Females had a more valgus alignment with a mTFA of 0.5 ± 2.9° while males had a more varus alignment with a mTFA of -1.7 ± 2.9°. The anatomic tibiofemoral angle (aTFA) was 4.8 ± 2.6°, the anatomic lateral distal femoral angle (aLDFA) measured 80.2 ± 2.2°, and the anatomical-mechanical angle (AMA) was 5.4 ± 0.7°. The prevalence of constitutional varus was 18%. The effect of rotation on the rotated scans led to statistically significant differences relative to the 0° measurement for all measurements. These effects may be small, and their clinical importance is unknown. CONCLUSIONS: This study provides new information on standardized measures of lower extremity alignment and the relationship between discreet axial rotations of the entire lower extremity and these parameters.

Femoroacetabular impingement: current concepts in diagnosis and treatment.

EDUCATIONAL OBJECTIVES: As a result of reading this article, physicians should be able to: 1. Identify the etiology of femoroacetabular impingement. 2. Assess femoroacetabular impingement on physical examination. 3. Recognize femoroacetabular impingement on imaging studies. 4. Discuss modern techniques to effectively treat femoroacetabular impingement, both open and arthroscopic. Femoroacetabular impingement (FAI) is a recently proposed concept describing abnormal anatomic relationships within the hip joint that may lead to articular damage. Impingement is caused by bony deformities or spatial malorientation of the femoral head-neck junction and/or the acetabulum. These abnormalities lead to pathologic contact and shearing forces at the acetabular labrum and cartilage during physiological hip motion. There is an increasing body of evidence that these forces lead to cartilage wear and eventual osteoarthritis. Treatment options for FAI are evolving rapidly. Although the gold standard remains open hip dislocation, arthroscopic techniques have shown significant promise. It is possible that early recognition and treatment of subtle deformity about the hip may reduce the rate of hip osteoarthritis in the future.

Periprosthetic supracondylar femur fracture treated with spanning external fixation.

Periprosthetic supracondylar fractures of the femur after total knee arthroplasty represent a devastating complication for the patient and a technical challenge for the surgeon. Treatment is often complicated by advanced patient age, retained cement, and accompanying osteoporosis. We present the case of a 54-year-old woman with a comminuted fracture of the distal femur just above a total knee prosthesis. She had a complex past medical history, including extensive coronary artery disease, morbid obesity, chronic osteoporosis, anemia, diabetes, and rheumatoid arthritis. She was a Jehovah's Witness and thus refused all blood products. Given her medical history, religious preferences, and fracture comminution, a spanning external fixator was used. She completed fracture union with an excellent clinical and radiographic result at 2 years.

Management of incarcerating pincer-type femoroacetabular impingement with hip arthroscopy.

This report describes the arthroscopic management of a case of incarcerating pincer-type femoroacetabular impingement. The hip joint had a marked restriction of range of motion and secondary pain as a result of osteophytes wrapping around the femoral head down the femoral neck. The patient was treated with staged bilateral hip arthroscopy. The procedures were initially performed through the peripheral compartment to remove the incarcerating acetabular rim, followed by arthroscopy of the central compartment with acetabuloplasty and femoral head osteochondroplasty. The patient's treatment has led to an excellent clinical and radiographic result at 24 months' follow-up despite an unrelated pelvic fracture sustained in the postoperative period. This technique emphasizes the capabilities of hip arthroscopy in advanced cases of femoroacetabular impingement as an alternative to arthroplasty for patients with healthy articular cartilage.

Younger age is associated with a higher risk of early periprosthetic joint infection and aseptic mechanical failure after total knee arthroplasty.

BACKGROUND: Although early aseptic mechanical failure after total knee arthroplasty has been reported in younger patients, it is unknown whether early revision due to periprosthetic joint infection is more or less frequent in this patient subgroup. The purpose of this study was to determine whether the incidence of early periprosthetic joint infection requiring revision knee surgery is significantly different in patients younger than fifty years of age compared with older patients following primary unilateral total knee arthroplasty. METHODS: A large population-based study was conducted with use of the California Patient Discharge Database, which allows serial linkage of all discharge data from nonfederal hospitals in the state over time. Patients undergoing primary unilateral total knee arthroplasty during 2005 to 2009 were identified. Principal outcomes were partial or complete revision arthroplasty due to periprosthetic joint infection or due to aseptic mechanical failure within one year. Multivariate analysis included risk adjustment for important demographic and clinical variables. The effect of hospital total knee arthroplasty volume on the outcomes of infection and mechanical failure was analyzed with use of hierarchical modeling. RESULTS: At one year, 983 (0.82%) of 120,538 primary total knee arthroplasties had undergone revision due to periprosthetic joint infection and 1385 (1.15%) had undergone revision due to aseptic mechanical failure. The cumulative incidence in patients younger than fifty years of age was 1.36% for revision due to periprosthetic joint infection and 3.49% for revision due to aseptic mechanical failure. In risk-adjusted models, the risk of periprosthetic joint infection was 1.8 times higher in patients younger than fifty years of age (odds ratio = 1.81, 95% confidence interval = 1.33 to 2.47) compared with patients sixty-five years of age or older, and the risk of aseptic mechanical failure was 4.7 times higher (odds ratio = 4.66, 95% confidence interval = 3.77 to 5.76). The rate of revision due to infection at hospitals in which a mean of more than 200 total knee arthroplasties were performed per year was lower than the expected (mean) value (p = 0.04). CONCLUSIONS: Patients younger than fifty years of age had a significantly higher risk of undergoing revision due to periprosthetic joint infection or to aseptic mechanical failure at one year after primary total knee arthroplasty.

What is normal femoral head/neck anatomy? An analysis of radial CT reconstructions in adolescents.

BACKGROUND: Cam morphology in femoroacetabular impingement has been implicated in the development of osteoarthritis. The alpha angle and femoral head/neck offset are widely used to determine femoral head asphericity. To our knowledge, no study has evaluated the alpha angle circumferentially using three-dimensional imaging in a population of healthy individuals of adolescent age. QUESTIONS/PURPOSES: We sought to (1) determine normal values for the alpha angle in adolescents, (2) define the location along the neck with the highest alpha angle, and (3) determine normal femoral head and neck radii and femoral head/neck offset. METHODS: Fifty CT scans from a database of scans obtained for reasons not related to hip pain were studied. The average age of the subjects was 15 years (range, 14-16 years). Alpha angle and femoral head/neck offset were measured circumferentially. RESULTS: The alpha angle averaged 40.66 ± 4.46 mm for males and 37.77 ± 5.65 mm for females. The alpha angle generally was highest between the 11:40 and 12:40 o'clock and between the 6:00 and 7:40 o'clock positions. The femoral head radius was 24.53 ± 1.74 mm for males and 21.94 ± 1.13 mm for females, and the femoral neck radius was 16.14 ± 2.32 mm for males and 13.82 ± 2.38 mm for females. The mean femoral head/neck offset was 8.39 ± 1.97 mm for males and 8.13 ± 2.27 mm for females. CONCLUSIONS: In this healthy population of 14- to 16-year-old subjects, the highest alpha angle was at the superior and inferior aspects of the heads rather than at the anterosuperior aspect. This information will provide benchmark values for distinction between normal and abnormal morphologic features of the femoral head.

Patellar polyethylene spinout after low-contact stress, high-congruity, mobile-bearing patellofemoral arthroplasty.

A low-contact stress, high-congruity, mobile-bearing patellofemoral joint arthroplasty decreases the contact force in the patellofemoral joint, theoretically reducing patellar polyethylene wear and increasing implant longevity. This article describes the case of a 47-year-old obese woman who presented with pain and loss of extension after a low-contact stress, high-congruity, mobile-bearing patellofemoral joint arthroplasty. Radiographs revealed dislocation (ie, spinout) of the patellar polyethylene. Patellar polyethylene spinout is a rare complication of metal-backed, mobile-bearing patellar resurfacing. Theoretically, patellar polyethylene spinout in low-contact stress, high-congruity, mobile-bearing patellofemoral arthroplasty is related to implant design and the placement of the metal base plate. Ultimately, the articulation of low-contact stress, high-congruity, mobile-bearing patellofemoral arthroplasty may be too congruent to resist the forces of the patellofemoral joint, particularly in patients who are obese, and the patellar rotation allowed by this articulation may not be sufficient for all patients. Should patellar spinout occur, replacement of the polyethylene is not sufficient to correct the problem; hence, revision of the patellar and trochlear components is required because it remains unclear whether failure is secondary to patellar or trochlear design deficiencies.

A population-based comparison of the incidence of adverse outcomes after simultaneous-bilateral and staged-bilateral total knee arthroplasty.

BACKGROUND: It is unclear whether simultaneous-bilateral total knee arthroplasty is as safe as staged-bilateral arthroplasty is. We are aware of no randomized trials comparing the safety of these surgical strategies. The purpose of this study was to retrospectively compare these two strategies, with use of an intention-to-treat approach for the staged-bilateral arthroplasty cohort. METHODS: We used linked hospital discharge data to compare the safety of simultaneous-bilateral and staged-bilateral knee arthroplasty procedures performed in California between 1997 and 2007. Estimates were generated to take into account patients who had planned to undergo staged-bilateral arthroplasty but never underwent the second procedure because of death, a major complication, or elective withdrawal. Hierarchical logistic regression modeling was used to adjust the comparisons for patient and hospital characteristics. The principal outcomes of interest were death, a major complication involving the cardiovascular system, and a periprosthetic knee infection or mechanical malfunction requiring revision surgery. RESULTS: Records were available for 11,445 simultaneous-bilateral arthroplasty procedures and 23,715 staged-bilateral procedures. On the basis of an intermediate estimate of the number of complications that occurred after the first procedure in a staged-bilateral arthroplasty, patients who underwent simultaneous-bilateral arthroplasty had a significantly higher adjusted odds ratio (OR) of myocardial infarction (OR = 1.6, 95% confidence interval [CI] = 1.2 to 2.2) and of pulmonary embolism (OR = 1.4, 95% CI = 1.1 to 1.8), similar odds of death (OR = 1.3, 95% CI = 0.9 to 1.9) and of ischemic stroke (OR = 1.0, 95% CI = 0.6 to 1.6), and significantly lower odds of major joint infection (OR = 0.6, 95% CI = 0.5 to 0.7) and of major mechanical malfunction (OR = 0.7, 95% CI = 0.6 to 0.9) compared with patients who planned to undergo staged-bilateral arthroplasty. The unadjusted thirty-day incidence of death or a coronary event was 3.2 events per thousand patients higher after simultaneous-bilateral arthroplasty than after staged-bilateral arthroplasty, but the one-year incidence of major joint infection or major mechanical malfunction was 10.5 events per thousand lower after simultaneous-bilateral arthroplasty. CONCLUSIONS: Simultaneous-bilateral total knee arthroplasty was associated with a clinically important reduction in the incidence of periprosthetic joint infection and malfunction within one year after arthroplasty, but it was associated with a moderately higher risk of an adverse cardiovascular outcome within thirty days. If patients who are at higher risk for cardiovascular complications can be identified, simultaneous-bilateral knee arthroplasty may be the preferred surgical strategy for the remaining lower-risk patients.

Computer-assisted navigation of total knee arthroplasty for osteoarthritis in a patient with severe posttraumatic femoral deformity.

In the setting of extraarticular deformities of the knee, total knee arthroplasty (TKA) is difficult, as anatomical abnormalities obstruct identification of alignment landmarks and may preclude the use of traditional instrumentation. The long-term clinical value of computer assistance for TKA is a point of ongoing controversy. Few reports describe the use of computer-assisted orthopedic surgery as a method to decrease alignment outliers in TKA with associated posttraumatic deformities. In this report, a 70-year-old woman who had a severe distal femoral deformity from a previous open fracture underwent computer-assisted TKA for osteoarthritis. The use of a computer-assisted navigation system achieved a high degree of accuracy relative to the desired target alignment and led to improved function in a patient in which standard instrumentation was not feasible.

Intermediate-term radiographic and patient outcomes in revision hip arthroplasty with a modular calcar design and porous plasma coating.

This study is a retrospective evaluation of the intermediate-term results of 26 consecutive revision total hip arthroplasties performed with a modular titanium, uncemented femoral component. The average patient age at the time of revision total hip arthroplasty was 72 years, and there were an equal number of males and females. The mean follow-up was 5.7 years (ranging from 4 to 11 years). No re-revision was necessary during this follow-up time. The mean Harris hip score improved significantly (preoperative and postoperative score was 50.7 and 89.6, respectively; P < .001). Postoperatively, Short Form 36 functional scores averaged 67.7 across 9 functional parameters. Our observed low revision rate and favorable patient-reported outcome scores support the continuous use of modular titanium, uncemented femoral components in revision total hip arthroplasty.

Multilevel measurement of acetabular version using 3-D CT-generated models: implications for hip preservation surgery.

BACKGROUND: Numerous structural deformities of the acetabulum are associated with hip osteoarthritis (OA). Acetabular retroversion has been implicated in the development of femoroacetabular impingement. However, it is unknown if retroversion occurs from isolated excessive bone in the superior acetabulum or a torsional phenomenon of the entire pelvic segment. QUESTIONS/PURPOSES: A method was developed to measure acetabular version (AV) using 3-D models thus eliminating positional factors. This method was used to determine if acetabular retroversion is an isolated entity or an effect involving the entire pelvic segment containing the acetabulum. METHOD: Fifty pelvic CT scans were selected from a large database. Measurements were performed for abduction, ischial spine position, and AV at multiple levels. The relationships between anteversion at multiple levels and between midacetabular anteversion and ischial spine position were analyzed. RESULTS: The mean upper and midlevel acetabular anteversion values were 14.4° ± 10.5° and 21.3° ± 5.8°, respectively. The mean abduction was 39.7° ± 4.3°. The prevalence of acetabular retroversion was 7%. Females had greater anteversion than males at all levels. Correlations were found between Levels 1 and 4 version (r = 0.74) and the ischial spine index and Level 4 version (r = 0.67). CONCLUSIONS: These data suggest retroversion involves the acetabulum at all levels and includes the entire pelvic segment containing the acetabulum and the ischial spine. CLINICAL RELEVANCE: These data are relevant for surgeons in providing targets for normal positioning of the acetabulum during periacetabular osteotomies and acetabular recontouring procedures.

Rabbit trochlear model of osteochondral allograft transplantation.

Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft-host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host-graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host-graft bone interface available for analysis.