As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA) and collagen. Chondrocytes and mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture, with accelerated cell growth seen with inclusion of cell spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion, we developed novel composite bioinks that can be triple-crosslinked, facilitating successful chondrocyte and MSC growth in 3D bioprinted scaffolds and in vitro repair of an osteochondral defect model. This offers hope for a new approach to treating AC defects.
There is a longstanding presumed association between obesity, complications, and revision surgery in primary knee arthroplasty. This has more recently been called into question, particularly in centres where a high volume of arthroplasty is performed. We investigated the correlation between Body Mass Index (BMI), mortality, and revision surgery. This was a cohort study of at least 10 years following primary knee arthroplasty from a single high volume arthroplasty unit. Mortality and revision rates were collected from all patients who underwent primary knee arthroplasty between 2009 and 2010. Kaplan Meier analysis was performed. There were 1161 female and 948 male patients with a mean age of 69 (21 to 97). All cause survivorship excluding mortality was 97.2% up to 13yrs with a minimum of 10 years. The revision rate in this series was 2.8% with no significant difference in revision rates after 10 year between patients with BMI above and below 40 (p=0.438). There was no significant difference in 10–year mortality between patients above and below a BMI of 40 (p=0.238). This study shows no significant difference in the long term survival of total knee replacement between patients with normal and high BMI. Careful consideration should be given before rationing surgery based on BMI alone.
Antimicrobial resistance (AMR) is projected to result in 10 million deaths every year globally by 2050. Without urgent action, routine orthopaedic operations could become high risk and musculoskeletal infections incurable in a “post-antibiotic era.” However, current methods of studying AMR processes including bacterial biofilm formation are 2D in nature, and therefore unable to recapitulate the 3D processes within Within this study, 3D printing was applied for the first time alongside a custom-developed bioink to bioprint 3D bacterial biofilm constructs from clinically relevant species including In conclusion, mature bacterial biofilm constructs were reproducibly 3D bioprinted for the first time using clinically relevant bacteria. This methodology allows the study of antimicrobial biofilm penetration in 3D, and potentially aids future antimicrobial research, replicating joint infection more closely than current 2D culture models. Furthermore, by deploying Raman spectroscopy in a novel fashion, it was possible to diagnose 3D bioprinted biofilm infections within a joint replacement model.
Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. The need for a novel, cost effective treatment option for osteochondral defects has therefore never been greater. As an emerging technology, three-dimensional (3D) bioprinting has the capacity to deposit cells, extracellular matrices and other biological materials in user-defined patterns to build complex tissue constructs from the “bottom up”. Through use of extrusion bioprinting and fused deposition modelling (FDM) 3D printing, porous 3D scaffolds were successfully created in this study from hydrogels and synthetic polymers. Mesenchymal stem cells (MSCs) seeded onto polycaprolactone scaffolds with defined pore sizes and porosity maintained viability over a 7-day period, with addition of alginate hydrogel and scaffold surface treatment with NaOH increasing cell adhesion and viability. MSC-laden alginate constructs produced via extrusion bioprinting also maintained structural integrity and cell viability over 7 days in vitro culture. Growth within osteogenic media resulted in successful osteogenic differentiation of MSCs within scaffolds compared to controls (p<0.001). MSC spheroids were also successfully created and bioprinted within a novel, supramolecular hydrogel with tunable stiffness. In conclusion, 3D constructs capable of supporting osteogenic differentiation of MSCs were biofabricated via FDM and extrusion bioprinting. Future work will look to increase osteochondral construct size and complexity, whilst maintaining cell viability.
Conventional computer navigation systems using bone fixation have been validated in measuring anteroposterior (AP) translation of the tibia. Recent developments in non-invasive skin-mounted systems may allow quantification of AP laxity in the out-patient setting. We tested cadaveric lower limbs (n=12) with a commercial image free navigation system using passive trackers secured by bone screws. We then tested a non-invasive fabric-strap system. The lower limb was secured at 10° intervals from 0° to 60° knee flexion and 100N of force applied perpendicular to the tibial tuberosity using a secured dynamometer. Repeatability coefficient was calculated both to reflect precision within each system, and demonstrate agreement between the two systems at each flexion interval. An acceptable repeatability coefficient of ≤3mm was set based on diagnostic criteria for ACL insufficiency when using other mechanical devices to measure AP tibial translation. Precision within the individual invasive and non-invasive systems measuring AP translation of the tibia was acceptable throughout the range of flexion tested (repeatability coefficient ≤1.6 mm). Agreement between the two systems was acceptable when measuring AP laxity between full extension and 40° knee flexion (repeatability coefficient ≤2.1 mm). Beyond 40° of flexion, agreement between the systems was unacceptable (repeatability coefficient >3 mm). These results indicate that from full knee extension to 40° flexion, non-invasive navigation-based quantification of AP tibial translation is as accurate as the standard invasive system, particularly in the clinically and functionally important range of 20° to 30° knee flexion. This could be useful in diagnosis and post-operative follow-up of ACL pathology.
Post operative warfarinisation of elective arthroplasty patients delays their discharge. We retrospectively analysed all patients who required warfarinisation post surgery from April to September 2011. We identified the number of extra days stayed for the sole purpose of warfarinisation (i.e. after discharge by Physiotherapy and Occupational Therapy) and estimated the cost implications of this extended stay. 76 patients were warfarinised post operation, mean age 70.6 years (50–87) with 42 females and 34 males, 37 THR and 33 TKR. The mean extra days stayed was 3.1 (range 0 to 9). Atrial fibrillation and previous venous thromboembolism (DVT/PE) were the most common indication, 78%, followed by a current episode of DVT/PE, 11%. The nature of joint replacement made no difference to the extra days stayed (3.1 for THR and 2.9 for TKR) or the INR (2.27 in both groups) at discharge. Random loading dose instead of the recommended 5 mg of warfarin resulted in prolonged stay, 4.5 days compared to 3 days otherwise. The approximate cost per inpatient day is £500 (£137 nursing, £163 medical and £200 for facilities). From our results this amounts to £1500 per patient and £228,000 a year. In addition, there is a loss of income as the bed occupancy means not being able to undertake another arthroplasty surgery (£3,600 per patient) and possible failure to achieve waiting time targets. We conclude that substantial financial and resource savings can be made if warfarinisation is undertaken at the community level.
