Impact of interstitial flow on cartilage matrix synthesis and NF-kB transcription factor mRNA expression in a novel perfusion bioreactor.

This work is focused on designing an easy-to-use novel perfusion system for articular cartilage (AC) tissue engineering and using it to elucidate the mechanism by which interstitial shear upregulates matrix synthesis by articular chondrocytes (AChs). Porous chitosan-agarose (CHAG) scaffolds were synthesized and compared to bulk agarose (AG) scaffolds. Both scaffolds were seeded with osteoarthritic human AChs and cultured in a novel perfusion system with a medium flow velocity of 0.33 mm/s corresponding to 0.4 mPa surfice shear and 40 mPa CHAG interstitial shear. While there were no statistical differences in cell viability for perfusion versus static cultures for either scaffold type, CHAG scaffolds exhibited a 3.3-fold higher (p < 0.005) cell viability compared to AG scaffold cultures. Effects of combined superficial and interstitial perfusion for CHAG showed 150- and 45-fold (p < 0.0001) increases in total collagen (COL) and 13- and 2.2-fold (p < 0.001) increases in glycosaminoglycans (GAGs) over AG non-perfusion and perfusion cultures, respectively, and a 1.5-fold and 3.6-fold (p < 0.005) increase over non-perfusion CHAG cultures. Contrasting CHAG perfusion and static cultures, chondrogenic gene comparisons showed a 3.5-fold increase in collagen type II/type I (COL2A1/COL1A1) mRNA ratio (p < 0.05), and a 1.3-fold increase in aggrecan mRNA. Observed effects are linked to NF-κB signal transduction pathway inhibition as confirmed by a 3.2-fold (p < 0.05) reduction of NF-κB mRNA expression upon exposure to perfusion. Our results demonstrate that pores play a critical role in improving cell viability and that interstitial flow caused by medium perfusion through the porous scaffolds enhances the expression of chondrogenic genes and extracellular matrix through downregulating NF-κB1.

Enhanced matrix production by cocultivated human stem cells and chondrocytes under concurrent mechanical strain.

Conventional treatments of osteoarthritis have failed to re-build functional articular cartilage. Tissue engineering clinical treatments for osteoarthritis, including autologous chondrocyte implantation, provides an alternative approach by injecting a cell suspension to fill lesions within the cartilage in osteoarthritic knees. The success of chondrocyte implantation relies on the availability of chondrogenic cell lines, and their resilience to high mechanical loading. We hypothesize we can reduce the numbers of human articular chondrocytes necessary for a treatment by supplementing cultures with human adipose-derived stem cells, in which stem cells will have protective and stimulatory effects on mixed cultures when exposed to high mechanical loads, and in which coculture will enhance production of requisite extracellular matrix proteins over those produced by stretched chondrocytes alone. In this work, adipose-derived stem cells and articular chondrocytes were cultured separately or cocultivated at ratios of 3:1, 1:1, and 1:3 in static plates or under excessive cyclic tensile strain of 10% and results were compared to culturing of both cell types alone with and without cyclic strain. Results indicate 75% of chondrocytes in engineered articular cartilage can be replaced with stem cells with enhanced collagen over all culture conditions and glycosaminoglycan content over stretched cultures of chondrocytes. This can be done without observing adverse effects on cell viability. Collagen and glycosaminoglycan secretion, when compared to chondrocyte alone under 10% strain, was enhanced 6.1- and 2-fold, respectively, by chondrocytes cocultivated with stem cells at a ratio of 1:3.

Platelet-rich plasma does not decrease blood loss in total knee arthroplasty.

This study was designed to assess the use of platelet-rich plasma (PRP) during primary total knee arthroplasty (TKA). The authors hypothesized that this would result in less blood loss and greater hemoglobin and hematocrit levels at discharge and would potentially decrease the length of hospital stay. Leukocyte rich PRP was used during the procedure and at wound closure. Two surgeons performed all procedures in a similar fashion. Two different TKA implants were used. Each surgeon used the same implant throughout the study. A limited medial parapatellar approach was used and drains were used at closure. No tranexamic acid preparations were used. Continuous passive motion machines were used in all patients during their hospital stay. A total of 102 consecutive TKAs were performed. The study group (n=46) consecutively received the PRP injections during the TKA, whereas the control group (n=47) did not. Hemoglobin and hematocrit levels were obtained pre- and postoperatively. Estimated blood loss was recorded during surgery, and the auto-collection reinfusion drain system output was measured. The length of hospital stay was collected and recorded. The study showed that hemoglobin and hematocrit levels were not different when comparing study and control groups. Age and sex differences were insignificant. Finally, no statistical difference was seen for the estimated blood loss and hospital stay between the 2 groups. Platelet-rich plasma use during TKA does not decrease hospital stay or reduce estimated blood loss in the perioperative period.

Rehabilitation of the osteoarthritic patient: focus on the knee.

This article reviews the factors involved in the rehabilitation process of the knee. Use of patient education, pain management, restoration of range of motion, and strengthening within the foundation of an aerobic fitness program are discussed.

Predictors of paralysis in the rheumatoid cervical spine in patients undergoing total joint arthroplasty.

BACKGROUND: Rheumatoid arthritis is sometimes associated with radiographic evidence of instability of the cervical spine, most commonly an abnormal subluxation between vertebrae. When this instability compromises the space that is available for the spinal cord, it may be predictive of paralysis. However, the prevalence of radiographic signs of instability that are predictive of paralysis among patients with nonspinal orthopaedic manifestations of rheumatoid arthritis is unknown. METHODS: Radiographs of the cervical spine of patients with rheumatoid arthritis who had undergone total joint arthroplasty over a five-year period were retrospectively reviewed. The radiographs were evaluated for predictors of paralysis (a posterior atlantodental interval of <14 mm or a subaxial space available for the cord measuring <14 mm) and were compared with traditional parameters of instability (an anterior atlantodental interval of >3 mm or subaxial subluxation of >3 mm). RESULTS: Forty-nine of the sixty-five patients who were identified had flexion and extension lateral radiographs available for review. Only one of these patients had a posterior atlantodental interval of <14 mm, and only three had a space available for the cord that measured <14 mm at one level or more. In comparison, twenty patients had radiographic evidence of instability on the basis of traditional parameters. CONCLUSIONS: Although nearly one-half of the patients in the present study had radiographic evidence of cervical instability on the basis of traditional measurements, only four patients (8%) had a radiographic finding that was predictive of paralysis. Thus, while radiographic evidence of cervical instability was not infrequent in this population of patients who underwent total joint arthroplasty for rheumatoid arthritis, radiographic predictors of paralysis were much less common.