Anish K. Amin

Unicompartmental or total knee arthroplasty?: Results from a matched study.

There are few direct comparative studies evaluating results after unicompartmental knee arthroplasty and total knee arthroplasty. We determined the active range of motion, Knee Society score, and 5-year survivorship rate after 54 consecutive unilateral unicompartmental knee arthroplasties compared with a matched group of 54 unilateral total knee arthroplasties. The two groups of patients were matched for age, gender, body mass index, preoperative active range of movement, and preoperative Knee Society scores. All patients had osteoarthritis of the knee. Patients were assessed prospectively at 6, 18, 36, and 60 months postoperatively, and the mean followup was 59 months in both groups. The mean postoperative active range of motion was greater after unicompartmental knee arthroplasty, but there were no differences in the overall Knee Society knee and function scores. The 5-year survivorship rate based on revision for any reason was 88% for unicompartmental knee arthroplasty and 100% for total knee arthroplasty. The worst case 5-year survivorship rate, assuming all patients lost to followup had revision surgery, was 85% for unicompartmental knee arthroplasty and 98% for total knee arthroplasty. Total knee arthroplasty was a more reliable procedure. Midterm clinical outcomes were similar for both procedures, but the complication rate may be greater for unicompartmental knee arthroplasty. Level of evidence:Therapeutic Level III. See the Guidelines for Authors for a complete description of levels of evidence.

Osmolarity influences chondrocyte death in wounded articular cartilage

BACKGROUND Mechanical injury results in chondrocyte death in articular cartilage. The purpose of the present study was to determine whether medium osmolarity affects chondrocyte death in injured articular cartilage. METHODS Osteochondral explants (n = 48) that had been harvested from the metacarpophalangeal joints of three-year-old cows were exposed to media with varying osmolarity (0 to 480 mOsm) for ninety seconds to allow in situ chondrocytes to respond to the altered osmotic environment. Explants were then wounded with a scalpel through the full thickness of articular cartilage, incubated in the same media for 2.5 hours, and transferred to 340-mOsm Dulbeccos Modified Eagle Medium (control medium) with further incubation for seven days. The spatial distribution of in situ chondrocyte death, percentage cell death, and marginal cell death at the wounded cartilage edge were compared as a function of osmolarity and time (2.5 hours compared with seven days) with use of confocal laser scanning microscopy. RESULTS In situ chondrocyte death was mainly localized to the superficial tangential zone of injured articular cartilage for the range of medium osmolarities (0 to 480 mOsm) at 2.5 hours and seven days. Therefore, a sample of articular cartilage from the superficial region (which included the scalpel-wounded cartilage edge) was studied with use of confocal laser scanning microscopy to compare the effects of osmolarity on percentage and marginal cell death in the superficial tangential zone. Compared with the control explants exposed to 340-mOsm Dulbeccos Modified Eagle Medium, percentage cell death in the superficial tangential zone was greatest for explants exposed to 0-mOsm (distilled water) and least for explants exposed to 480-mOsm Dulbeccos Modified Eagle Medium at 2.5 hours (13.0% at 340 mOsm [control], 35.5% at 0 mOsm, and 4.3% at 480 mOsm; p <or= 0.02 for paired comparisons) and seven days (9.9% at 340 mOsm [control], 37.7% at 0 mOsm, and 3.5% at 480 mOsm; p <or= 0.01 for paired comparisons). Marginal cell death in the superficial tangential zone decreased with increasing medium osmolarity at 2.5 hours (p = 0.001) and seven days (p = 0.002). There was no significant change in percentage cell death from 2.5 hours to seven days for explants initially exposed to any of the medium osmolarities. CONCLUSIONS Medium osmolarity significantly affects chondrocyte death in wounded articular cartilage. The greatest chondrocyte death occurs at 0 mOsm. Conversely, increased medium osmolarity (480 mOsm) is chondroprotective. The majority of cell death occurs within 2.5 hours, with no significant increase over seven days.

Chondrocyte survival in articular cartilage: THE INFLUENCE OF SUBCHONDRAL BONE IN A BOVINE MODEL

The aim of this study was to determine whether subchondral bone influences in situ chondrocyte survival. Bovine explants were cultured in serum-free media over seven days with subchondral bone excised from articular cartilage (group A), subchondral bone left attached to articular cartilage (group B), and subchondral bone excised but co-cultured with articular cartilage (group C). Using confocal laser scanning microscopy, fluorescent probes and biochemical assays, in situ chondrocyte viability and relevant biophysical parameters (cartilage thickness, cell density, culture medium composition) were quantified over time (2.5 hours vs seven days). There was a significant increase in chondrocyte death over seven days, primarily within the superficial zone, for group A, but not for groups B or C (p < 0.05). There was no significant difference in cartilage thickness or cell density between groups A, B and C (p > 0.05). Increases in the protein content of the culture media for groups B and C, but not for group A, suggested that the release of soluble factors from subchondral bone may have influenced chondrocyte survival. In conclusion, subchondral bone significantly influenced chondrocyte survival in articular cartilage during explant culture. The extrapolation of bone-cartilage interactions in vitro to the clinical situation must be made with caution, but the findings from these experiments suggest that future investigation into in vivo mechanisms of articular cartilage survival and degradation must consider the interactions of cartilage with subchondral bone.

Chondrocyte Death in Mechanically Injured Articular Cartilage―The Influence of Extracellular Calcium

Calcium is thought to be an important regulator of chondrocyte death associated with articular cartilage injury. Our objective was to determine the influence of extracellular calcium on chondrocyte death following mechanical injury. Using a surgically relevant model of sharp mechanical injury (with a scalpel) and confocal laser scanning microscopy (CLSM), in situ chondrocyte death was quantified within the full thickness of articular cartilage as a function of medium calcium concentration and time (2.5 h and 7 days). Exposure of articular cartilage to calcium‐free media (∼0 mM) significantly reduced superficial zone chondrocyte death after mechanical injury compared with exposure to calcium‐rich media (2–20 mM, ANOVA at 2.5 h, p = 0.002). In calcium‐rich media, although the extent of chondrocyte death increased with increasing medium calcium concentration, cell death remained localized to the superficial zone of articular cartilage over 7 days (ANOVA, p < 0.05). However, in calcium‐free media, there was an increase in chondrocyte death within deeper zones of articular cartilage over 7 days. The early (within hours) chondroprotective effect in calcium‐free media suggests that the use of joint irrigation solutions without added calcium may decrease chondrocyte death from mechanical injury during articular surgery. The delayed (within days) increase in chondrocyte death in calcium‐free media supports the use of calcium supplementation in media used during cartilage culture for tissue engineering or transplantation.

Hyperosmolarity protects chondrocytes from mechanical injury in human articular cartilage

The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces in situ chondrocyte death following a standardised mechanical injury produced by a scalpel cut compared with the same assault and exposure to normal saline (0.9%, 285 mOsm). Human cartilage explants were exposed to normal (control) and hyperosmotic 0.9% saline solutions for five minutes before the mechanical injury to allow in situ chondrocytes to respond to the altered osmotic environment, and incubated for a further 2.5 hours in the same solutions following the mechanical injury. Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline. These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair.

The use of hyperosmotic saline for chondroprotection: implications for orthopaedic surgery and cartilage repair

OBJECTIVE Articular cartilage may experience iatrogenic injury during routine orthopaedic/arthroscopic procedures. This could cause chondrocyte death, leading to cartilage degeneration and posttraumatic osteoarthritis. In an in vitro cartilage injury model, chondrocyte death was reduced by increasing the osmolarity of normal saline (NS), the most commonly-used irrigation solution. Here, we studied the effect of hyperosmolar saline (HS) on chondrocyte viability and cartilage repair in an in vivo injury model. DESIGN Cartilage injury was induced by a single scalpel cut along the patellar groove of 8 week old rats in the absence of irrigation or with either NS (300 mOsm) or HS (600 mOsm). The percentage of cell death (PCD) within the injured area was assessed using confocal microscopy. Repair from injury was evaluated by histology/immunostaining, and inflammatory response by histology, cytokine array analysis and ELISA (enzyme-linked immunosorbent assay). RESULTS The PCD in saline-irrigated joints was increased compared to non-irrigated (NI) joints [PCD = 20.8% (95%CI; 14.5, 27.1); PCD = 9.14% (95%CI; 6.3, 11.9); P = 0.0017]. However, hyperosmotic saline reduced chondrocyte death compared to NS (PCD = 10.4% (95%CI; 8.5, 12.3) P = 0.0024). Repair score, type II collagen and aggrecan levels, and injury width, were significantly improved with hyperosmotic compared to NS. Mild synovitis and similar changes in serum cytokine profile occurred in all operated joints irrespective of experimental group. CONCLUSIONS Hyperosmotic saline significantly reduced the chondrocyte death associated with scalpel-induced injury and enhanced cartilage repair. This irrigation solution might be useful as a simple chondroprotective strategy and may also reduce unintentional cartilage injury during articular reconstructive surgery and promote integrative cartilage repair, thereby reducing the risk of posttraumatic osteoarthritis.

Airflow accelerates bovine and human articular cartilage drying and chondrocyte death

OBJECTIVE Exposure of articular cartilage to static air results in changes to the extracellular matrix (ECM) and stimulates chondrocyte death, which may cause joint degeneration. However during open orthopaedic surgery, cartilage is often exposed to laminar airflow, which may exacerbate these damaging effects. We compared drying in static and moving air in terms of cartilage appearance, hydration and chondrocyte viability, and tested the ability of saline-saturated gauze to limit the detrimental effects of air exposure. DESIGN Articular cartilage from bovine metatarsophalangeal joints (N = 50) and human femoral heads (N = 6) was exposed for 90 min to (1) static air (2) airflow (up to 0.34 m/s), or (3) airflow (0.18 m/s), covered with gauze. Following air exposure, cartilage was also rehydrated (0.9% saline; 120 min) to determine the reversibility of drying effects. The influence of airflow was assessed by studying macroscopic appearance, and quantifying superficial zone (SZ) chondrocyte viability and cartilage hydration. RESULTS Airflow caused advanced changes to cartilage appearance, accelerated chondrocyte death, and increased dehydration compared to static air. These effects were prevented if cartilage was covered by saline-saturated gauze. Cartilage rehydration reversed macroscopic changes associated with drying but the chondrocyte death was not altered. Chondrocytes at the cut edge of cartilage were more sensitive to drying compared to cells distant from the edge. CONCLUSIONS Airflow significantly increased articular cartilage dehydration and chondrocyte death compared to static air. As laminar airflow is routinely utilised in operating theatres, it is essential that articular cartilage is kept wet via irrigation or by covering with saline-saturated gauze to prevent chondrocyte death.

Drying of open animal joints in vivo subsequently causes cartilage degeneration.

Objectives During open orthopaedic surgery, joints may be exposed to air, potentially leading to cartilage drying and chondrocyte death, however, the long-term effects of joint drying in vivo are poorly understood. We used an animal model to investigate the subsequent effects of joint drying on cartilage and chondrocytes. Methods The patellar groove of anaesthetised rats was exposed (sham-operated), or exposed and then subjected to laminar airflow (0.25m/s; 60 minutes) before wounds were sutured and animals recovered. Animals were monitored for up to eight weeks and then sacrificed. Cartilage and chondrocyte properties were studied by histology and confocal microscopy, respectively. Results Joint drying caused extensive chondrocyte death within the superficial regions of cartilage. Histology of dried cartilage demonstrated a loss of surface integrity at four weeks, fibrillations at eight weeks, and an increased modified Mankin score (p < 0.001). Cartilage thickness increased (p < 0.001), whereas chondrocyte density decreased at four weeks (p < 0.001), but then increased towards sham-operated levels (p < 0.01) at eight weeks. By week eight, chondrocyte pairing/clustering and cell volume increased (p < 0.05; p < 0.001, respectively). Conclusions These in vivo results demonstrated for the first time that as a result of laminar airflow, cartilage degeneration occurred which has characteristics similar to those seen in early osteoarthritis. Maintenance of adequate cartilage hydration during open orthopaedic surgery is therefore of paramount importance. Cite this article: Dr A. Hall. Drying of open animal joints in vivo subsequently causes cartilage degeneration. Bone Joint Res 2016;5:137–144. DOI: 10.1302/2046-3758.54.2000594.

The clustering and morphology of chondrocytes in normal and mildly degenerate human femoral head cartilage studied by confocal laser scanning microscopy

Chondrocytes are the major cell type present in hyaline cartilage and they play a crucial role in maintaining the mechanical resilience of the tissue through a balance of the synthesis and breakdown of extracellular matrix macromolecules. Histological assessment of cartilage suggests that articular chondrocytes in situ typically occur singly and demonstrate a rounded/elliptical morphology. However, there are suggestions that their grouping and fine shape is more complex and that these change with cartilage degeneration as occurs in osteoarthritis. In the present study we have used confocal laser scanning microscopy and fluorescently labelled in situ human chondrocytes and advanced imaging software to visualise chondrocyte clustering and detailed morphology within grade‐0 (non‐degenerate) and grade‐1 (mildly degenerate) cartilage from human femoral heads. Graded human cartilage explants were incubated with 5‐chloromethylfluorescein diacetate and propidium iodide to identify the morphology and viability, respectively, of in situ chondrocytes within superficial, mid‐ and deep zones. In grade‐0 cartilage, the analysis of confocal microscope images showed that although the majority of chondrocytes were single and morphologically normal, clusters (i.e. three or more chondrocytes within the enclosed lacunar space) were occasionally observed in the superficial zone, and 15–25% of the cell population exhibited at least one cytoplasmic process of ~ 5 μm in length. With degeneration, cluster number increased (~ 50%) but not significantly; however, the number of cells/cluster (P < 0.001) and the percentage of cells forming clusters increased (P = 0.0013). In the superficial zone but not the mid‐ or deep zones, the volume of clusters and average volume of chondrocytes in clusters increased (P < 0.001 and P < 0.05, respectively). The percentage of chondrocytes with processes, the number of processes/cell and the length of processes/cell increased in the superficial zone of grade‐1 cartilage (P = 0.0098, P = 0.02 and P < 0.001, respectively). Processes were categorised based on length (L0 – no cytoplasmic processes; L1 < 5 μm; 5 < L2 ≤ 10 μm; 10 < L3 ≤ 15 μm; L4 > 15 μm). With cartilage degeneration, for chondrocytes in all zones, there was a significant decrease (P = 0.015) in the percentage of chondrocytes with ‘normal’ morphology (i.e. L0), with no change in the percentage of cells with L1 processes; however, there were significant increases in the other categories. In grade‐0 cartilage, chondrocyte clustering and morphological abnormalities occurred and with degeneration these were exacerbated, particularly in the superficial zone. Chondrocyte clustering and abnormal morphology are associated with aberrant matrix metabolism, suggesting that these early changes to chondrocyte properties may be associated with cartilage degeneration.

Iatrogenic articular cartilage injury: the elephant in the operating theatre: the surgeons' role in chondroprotection

Arthroscopy of the synovial joint is the most frequently performed orthopaedic procedure in the developed world.[1][1] A variety of soft-tissue and articular pathologies relating to the hip,[2][2] knee, ankle, shoulder, elbow and wrist joints can be treated arthroscopically.[1][1] While advances in