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Biomedical subjects

Anthony Ratcliffe

Publications and source records attributed to Anthony Ratcliffe.

11 recordsLinked to original sources
PubMed2006

The inferior glenohumeral ligament: a correlative investigation.

The inferior glenohumeral ligament (IGHL) was investigated by correlating the biomechanical properties, biochemical composition, and histologic morphology of its 3 anatomic regions (superior band, anterior axillary pouch, and posterior axillary pouch) in 8 human cadaveric shoulders. The overall biochemical composition of the IGHL appeared similar to other ligaments, with average water content of 80.9 +/- 2.5%, collagen content of 80.0 +/- 9.2%, and crosslinks of 0.715 +/- 0.13 mol/mol collagen. The proteoglycan content was highest in the superior band (2.73 +/- 0.7 mg/g dry weight) and may, in part, explain its viscoelastic behavior. Histologic analysis demonstrated longitudinally organized fiber bundles that were more uniform in the mid-substance but more interwoven and less uniformly oriented near the insertion sites. The superior band had the most pronounced fiber bundle interweaving, while crimping was more evident in the anterior axillary pouch. Elastin was identified in each of the regions. Tensile testing demonstrated a trend toward higher ultimate tensile stress (16.9 +/- 7.9 MPa) and tensile modulus (130.3 +/- 47.9 MPa) in the superior band compared to the axillary pouch. The mean ultimate tensile strain of the IGHL was 16.8 +/- 4.6%. These complex IGHL properties may help to explain its unique functions in stabilizing the shoulder in different arm positions and at different rates of loading, including the failure patterns seen clinically, as in Bankart lesions (insertion site) versus capsular stretching (ligament substance).

Aged↗
PubMed2006

The effect of gamma irradiation on anterior cruciate ligament allograft biomechanical and biochemical properties in the caprine model at time zero and at 6 months after surgery.

BACKGROUND: High levels of gamma irradiation are required to eliminate the risk of bacterial and viral transmission during implantation of musculoskeletal allografts. The effects of high levels of gamma irradiation on anterior cruciate ligament allograft biomechanics are still not known. HYPOTHESIS: High-dose gamma irradiation (4 Mrad) adversely affects anterior cruciate ligament allograft biomechanics at surgery and at 6 months after surgery and affects biochemistry at 6 months. STUDY DESIGN: Controlled laboratory study. METHODS: Bilateral anterior cruciate ligament reconstructions were performed in 18 adult goats, with one knee receiving an irradiated patellar tendon allograft (4 Mrad) and the other receiving a frozen control allograft (0 Mrad). In 6 recipients (time zero group), graft pairs were tested immediately after sacrifice, and load relaxation of the femur-allograft-tibia preparation was measured during cyclic anterior displacement. Twelve recipients received bilateral anterior cruciate ligament reconstructions, staged 2 months apart, and were sacrificed a mean of 6 months postoperatively. Load relaxation and tensile failure testing were performed, followed by allograft biochemistry assessment. RESULTS: At time zero, irradiated grafts showed less load relaxation than did contralateral controls, but by 6 months, the trend had reversed because of decreases in control graft relaxation, with no changes in irradiated graft relaxation. By 6 months, irradiated grafts showed lower stiffness and maximum force compared to controls but no differences in modulus, maximum stress, or biochemistry. CONCLUSION: High levels of gamma irradiation affect anterior cruciate ligament allograft subfailure viscoelastic and structural properties but not material or biochemical properties over time. CLINICAL RELEVANCE: Although high levels of gamma irradiation may inactivate infectious agents, this treatment is not a feasible clinical option because of altered allograft biomechanics.

Animals↗
PubMed2003

Bone formation on tissue-engineered cartilage constructs in vivo: effects of chondrocyte viability and mechanical loading.

Interactions between bone and cartilage formation are critical during growth and fracture healing and may influence the functional integration of osteochondral repair constructs. In this study, the ability of tissue-engineered cartilage constructs to support bone formation under controlled mechanical loading conditions was evaluated using a lapine hydraulic bone chamber model. Articular chondrocytes were seeded onto polymer disks, cultured for 4 weeks in vitro, and then transferred to empty bone chambers previously implanted into rabbit femoral metaphyses. The effects of chondrocyte viability within the implanted constructs and in vivo mechanical loading on bone formation were tested in separate experiments. After 4 weeks in vivo, biopsies from the chambers consisted of a complex composite of bone, cartilage, and fibrous tissue, with bone forming in direct apposition to the cartilage constructs. Microcomputed tomography imaging of the chamber biopsies revealed that the implantation of viable constructs nearly doubled the bone volume fraction of the chamber tissue from 0.9 to 1.6% as compared with the implantation of devitalized constructs in contralateral control chambers. The application of an intermittent cyclic mechanical load was found to increase the bone volume fraction of the chamber tissue from 0.4 to 3.6% as compared with no-load control biopsies. The results of these experiments demonstrate that tissue-engineered cartilage constructs implanted into a well-vascularized bone defect will support direct appositional bone formation and that bone formation is significantly influenced by the viability of chondrocytes within the constructs and the local mechanical environment in vivo.

Animals↗
PubMed2002

A three-dimensional osteochondral composite scaffold for articular cartilage repair.

There is a recognized and urgent need for improved treatment of articular cartilage defects. Tissue engineering of cartilage using a cell-scaffold approach has demonstrated potential to offer an alternative and effective method for treating articular defects. We have developed a unique, heterogeneous, osteochondral scaffold using the TheriForm three-dimensional printing process. The material composition, porosity, macroarchitecture, and mechanical properties varied throughout the scaffold structure. The upper, cartilage region was 90% porous and composed of D,L-PLGA/L-PLA, with macroscopic staggered channels to facilitate homogenous cell seeding. The lower, cloverleaf-shaped bone portion was 55% porous and consisted of a L-PLGA/TCP composite, designed to maximize bone ingrowth while maintaining critical mechanical properties. The transition region between these two sections contained a gradient of materials and porosity to prevent delamination. Chondrocytes preferentially attached to the cartilage portion of the device, and biochemical and histological analyses showed that cartilage formed during a 6-week in vitro culture period. The tensile strength of the bone region was similar in magnitude to fresh cancellous human bone, suggesting that these scaffolds have desirable mechanical properties for in vivo applications, including full joint replacement.

Analysis of Variance↗
PubMed2002

Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage.

Static and dynamic compression are known to modulate the metabolism of articular cartilage. The present study focused on determining the effects of compressive loading on the metabolism of sulfated glycosaminoglycans (S-GAG) and protein in tissue engineered cartilage constructs. Cartilage constructs were subjected to static or dynamic compression for 24 h and radiolabeled with 35SO4 and 3H-proline to assess the total synthesis and percentage retention of S-GAG and total protein, respectively. Static compression at an amplitude of 50% suppressed the synthesis of both S-GAG and protein by 35% and 57%, respectively. Dynamic compression at an amplitude of 5% had stimulatory effects on synthesis that were dependent on the static offset compression amplitude (10% or 50%) and dynamic compression frequency (0.001 or 0.1 Hz). Thus, tissue engineered cartilage demonstrated the ability to respond to mechanical loading in a manner similar to that observed with articular cartilage. Mechanical loading may therefore potentially be used to modulate the growth of cartilaginous tissues in vitrd, potentially facilitating the culture of functional cartilage tissues suitable for implantation.

Animals↗
PubMed2002

Perfusion increases cell content and matrix synthesis in chondrocyte three-dimensional cultures.

This work examines the effect of perfusion on the cell content and sulfated glycosaminoglycan synthesis of ovine articular chondrocytes cultured on polyglycolic acid (PGA) scaffolds. Ovine chondrocytes were seeded onto the scaffolds and cultured for up to 9 days. During this time the cells were subjected to perfusion at velocities of up to 170 microm/s. The samples were radiolabeled with (35)SO(4) to quantify the overall synthesis of sulfated glycosaminoglycans (S-GAGs) and the retention of S-GAGs in the construct. The constructs were also analyzed for DNA as a measure of cellular content. Constructs subjected to perfusion during culture had significantly higher DNA contents than those cultured statically. Matrix metabolism was also modulated by perfusion, with this modulation depending on culture duration. Nine days of continuous perfusion increased S-GAG synthesis and deposition by approximately 40% when compared with static controls. However, perfusion at early time points (during the initial 3-day culture period) suppressed the synthesis and retention of S-GAGs when compared with controls. This work demonstrates the effects of perfusion on cartilage growth in vitro, illustrating the use of perfusion to modulate the growth of tissue-engineered cartilage constructs, and potentially enhance tissue growth in vitro.

Animals↗
PubMed2002

Bioreactors and bioprocessing for tissue engineering.

Bioreactor design in tissue engineering is complex, and at the early stages of its development. Design of biologically effective, yet scalable, devices requires intimate collaboration between engineers and biologists to ensure that all aspects are considered fully. Growth conditions, harvesting time, scale-up, storage, and sterility issues all need to be considered and incorporated into the design of bioreactors. Each tissue-engineered product will likely require individualized bioreactor design. However, without a comprehensive understanding of each of these components, bioreactor design and tissue growth to manufacture product will remain at a relatively rudimentary and limited level. Increased fundamental understanding of the issues can have a dramatic impact on the ability to generate tissue-engineered product safely, economically, and in the numbers that are required to fully address the patient populations in need.

Animals↗
PubMed2002

Fluid shear stress-induced alignment of cultured vascular smooth muscle cells.

The study objectives were to quantify the time- and magnitude-dependence of flow-induced alignment in vascular smooth muscle cells (SMC) and to identify pathways related to the orientation process. Using an intensity gradient method, we demonstrated that SMC aligned in the direction perpendicular to applied shear stress, which contrasts with parallel alignment of endothelial cells under flow SMC alignment varied with the magnitude of and exposure time to shear stress and is a continuous process that is dependent on calcium and cycloskeleton based mechanisms. A clear understanding and control of flow-induced SMC alignment will have implications for vascular tissue engineering.

Aminoquinolines↗
PubMed2002

Induction of apoptosis in vascular smooth muscle cells by mechanical stretch.

We studied the response of porcine vascular smooth muscle cells (PVSMCs) to cyclic sinusoidal stretch at a frequency of 1 Hz. Cyclic stretch with an area change of 25% caused an increase in PVSMC apoptosis, which was accompanied by sustained activation of c-Jun NH(2)-terminal kinases (JNK) and the mitogen-activated protein kinase p38. Cyclic stretch with an area change of 7% had no such effect. Infection of PVSMCs with recombinant adenoviruses expressing constitutively active forms of upstream molecules that activate JNK and p38 also led to apoptosis. The simultaneous blockade of both JNK and p38 pathways with adenovirus-mediated expression of dominant-negative mutants of c-Jun and p38 caused a significant decrease (to 1/2) of the apoptosis induced by 25% cyclic stretch. The 25% stretch also caused sustained clustering of tumor necrosis factor-alpha (TNF-alpha) receptor-1 and its association with TNF-alpha receptor-associated factor-2 (TRAF-2). Overexpressing the wild-type TRAF-2 in PVSMCs caused an increase in apoptosis. In contrast, the expression of a dominant-negative mutant of TRAF-2 attenuated stretch-induced apoptois. These results support the hypothesis that circumferential overload under hypertensive conditions induces a clustering of death receptors that cause vascular smooth muscle cell apoptosis.

Animals↗