Purpose Total knee arthroplasty (TKA) rates have increased substantially in the recent decades worldwide, with Germany being one of the leading countries in the prevalence of TKA. The aim of this study was to provide an overview of treatment changes during the last decade and to project the expected burden of primary and revision TKA (rTKA) for the next 30 years. Methods Comprehensive nationwide data from Germany was used to quantify primary and revision TKA rates as a function of age and gender. Projections were performed with use of a Poisson regression models and a combination of exponential smoothing and autoregressive integrated moving average models on historical procedure rates in relation to official population projections from 2020 to 2050. Results The incidence rate of primary TKAs is projected to increase by around 43% to 299 per 100,000 inhabitants [95% CI 231-368], leading to a projected total number of 225,957 primary TKAs in 2050 (95% CI 178,804-276,442). This increase has been related to a growing number of TKA performed in male patients, with the highest increase modelled in patients between 50 and 65 years of age. At the same time, the annual total number of revision procedures is forecast to increase even more rapidly by almost 90%, accounting for 47,313 (95% CI 15,741-78,885; IR = 62.7 per 100,000, 95% CI 20.8-104.5) procedures by 2050. Those numbers are primarily associated with a rising number of rTKAs secondary to periprosthetic joint infection (PJI). Conclusions Using this country-specific forecast approach, a rising number of primary TKA and an even more rapidly growing number of rTKA, especially for PJI, has been projected until 2050, which will inevitably provide a huge challenge for the future health care system. As many other industrialized nations will face similar demographic and procedure-specific developments, these forecasts should be alarming for many health care systems worldwide and emphasize the tremendous need for an appropriate financial and human resource management in the future. Level of evidence Level III, prognostic study, economic and decision analysis.
IntroductionTo date, no single most-appropriate factor or delivery method has been identified for the purpose of mesenchymal stem cell (MSC)-based treatment of cartilage injury. Therefore, in this study we tested whether gene delivery of the growth factor Indian hedgehog (IHH) was able to induce chondrogenesis in human primary MSCs, and whether it was possible by such an approach to modulate the appearance of chondrogenic hypertrophy in pellet cultures in vitro.MethodsFirst-generation adenoviral vectors encoding the cDNA of the human IHH gene were created by cre-lox recombination and used alone or in combination with adenoviral vectors, bone morphogenetic protein-2 (Ad.BMP-2), or transforming growth factor beta-1 (Ad.TGF-β1) to transduce human bone-marrow derived MSCs at 5 × 102 infectious particles/cell. Thereafter, 3 × 105 cells were seeded into aggregates and cultured for 3 weeks in serum-free medium, with untransduced or marker gene transduced cultures as controls. Transgene expressions were determined by ELISA, and aggregates were analysed histologically, immunohistochemically, biochemically and by RT-PCR for chondrogenesis and hypertrophy.ResultsIHH, TGF-β1 and BMP-2 genes were equipotent inducers of chondrogenesis in primary MSCs, as evidenced by strong staining for proteoglycans, collagen type II, increased levels of glycosaminoglycan synthesis, and expression of mRNAs associated with chondrogenesis. IHH-modified aggregates, alone or in combination, also showed a tendency to progress towards hypertrophy, as judged by the expression of alkaline phosphatase and stainings for collagen type X and Annexin 5.ConclusionAs this study provides evidence for chondrogenic induction of MSC aggregates in vitro via IHH gene delivery, this technology may be efficiently employed for generating cartilaginous repair tissues in vivo.
IHH gene transfer is effective to improve repair cartilage quality in vivo, whereas BMP2 treatment, carried the risk intralesional bone formation. Therefore IHH protein can be considered as an attractive alternative candidate growth factor for further preclinical research and development towards improved treatments for articular cartilage defects.
Objective As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors. Design Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box ( SOX ) 9 , transforming growth factor beta (TGFB) 1 or bone morphogenetic protein ( BMP) 2 cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP. The respective constructs were analyzed histologically, immunohistochemically, biochemically, and by qRT-PCR for chondrogenesis and hypertrophy. Results Chondrogenesis in MSCs was consistently and strongly induced in collagen I hydrogels by the transgenes SOX9 , TGFB1 and BMP2 as evidenced by positive staining for proteoglycans, chondroitin-4-sulfate (CS4) and collagen (COL) type II, increased levels of glycosaminoglycan (GAG) synthesis, and expression of mRNAs associated with chondrogenesis. The control groups were entirely non-chondrogenic. The levels of hypertrophy, as judged by expression of alkaline phosphatase (ALP) and COL X on both the protein and mRNA levels revealed different stages of hypertrophy within the chondrogenic groups ( BMP2 > TGFB1 > SOX9 ). Conclusions Different types of neocartilage with varying levels of hypertrophy could be generated from human MSCs in collagen hydrogels by transfer of genes encoding the chondrogenic factors SOX9 , TGFB1 and BMP2 . This technology may be harnessed for regeneration of specific zones of native cartilage upon damage.
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