Enhanced angiogenesis and osteogenesis may provide new strategies for the treatment of osteonecrosis. Synergistic effects of vascular endothelial growth factor (VEGF) and bone morphogenetic protein - 6 (BMP-6) on Introduction
Methods
The aim of the ongoing projects was to demonstrate the efficacy of autologous
Extensive bone defects, caused by severe trauma or resection of large bone tumors, are difficult to treat. Regenerative medicine, including stem cell transplantation, may provide a novel solution for these intractable problems and improve the quality of life in affected patients. Adipose-derived stromal/stem cells (ASCs) have been extensively studied as cell sources for regenerative medicine due to their excellent proliferative capacity and the ability to obtain a large number of cells with minimal donor morbidity. However, the osteogenic potential of ASCs is lower than that of bone marrow-derived stromal/stem cells. To address this disadvantage, our group has employed various methods to enhance osteogenic differentiation of ASCs, including factors such as bone morphogenetic protein or Vitamin D, coculture with
Heterotopic ossi?cation is the abnormal formation of bone in soft tissues and is a frequent complication of hip replacement surgery. Heterotopic ossi?cations are described to develop via endochondral ossification and standard treatment is administration of indomethacin. It is currently unknown how indomethacin influences heterotopic ossi?cation on a molecular level, therefore we aimed to determine whether indomethacin might influence heterotopic ossi?cation via impairing the chondrogenic phase of endochondral ossification. ATDC5, human
Abstract. Objectives. The enthesis is a specialised structure at the interface between bone and tendon with gradual integration to maintain functionality and integrity. In the process of fabricating an in-vitro model of this complex structure, this study aims to investigate growth and maturation of bone, tendon and BMSC spheroids followed by 3D mini-tissue production. Methods. Cell spheroids Spheroids of differentiated rat osteoblasts (dRObs), rat tendon fibroblasts (RTFs) and
INTRODUCTION. Bone marrow derived mesenchymal stem cells are a potential source of cells for the repair of articular cartilage defects. Hypoxia has been shown to improve chondrogenesis in adult stem cells. In this study we characterised
Introduction. Novel chondroitin sulphate (CS) sulphation motifs on cell-associated proteoglycans (PGs) have been shown to be putative biomarkers of progenitor/stem cell sub-populations (Hayes et al., 2007; Dowthwaite et al., 2005). Also, recent studies show that unique CS sulphation motifs are localized in putative stem/progenitor cell niches at sites of incipient articular cartilage & other musculoskeletal tissues (Hayes et al., 2011), which indicates their potential importance in cell differentiation during development. In this study, we investigated the importance of CS in the differentiation of
A rotator cuff tear is one of the most common traumatic and degenerative tendon injuries resulting in over 4.5 million physician visits in the US alone. Functional restoration of rotator cuff defects usually requires surgical repair, estimated at 300,000 cased in the US annually. However, postoperative retear of repaired tendons ranges from 20% in small to medium tears to over 90% in large and massive tears. Recently, augmentation with grafting materials to strengthen a reparable tear or to bridge an unrepairable defect has become a common and attractive strategy to reduce the retear rate, especially for large or massive tears. Current graft materials, however, have encountered great challenges in achieving these goals. To meet these challenges, we have developed an engineered tendon with layered tendon-fibrocartilage-bone composite (TFBC) from patellar-tibia unit revitalized by seeding
Collagen scaffolds are generally characterized by their random fibre distribution and weak mechanical properties, which makes them unsuitable as substitutes for highly anisotropic tissues such as cornea or tendon. Recently, we developed a technique to create collagen type I scaffolds with well-defined anisotropic micro-patterns. Porcine collagen was mixed with PBS10X, NaOH and one of the following cross-linkers: glutaraldehyde (GTA), genipin and 4-arm polyethylene glycol (4SP). The resulting mixture was casted on micro-grooved (2×2×2 μm) polydimethylsiloxane (PDMS) moulds and allowed to dry in a laminar flow hood to obtain 5mg/ml collagen films. Different pH, temperatures (Tº), and cross-linker concentrations were tested in the process. Collagen gelation kinetics was analysed with rheometry and surface topography was assessed with scanning electron microscopy (SEM). Human
Among the innovative therapeutic techniques in orthopedics, a considerable interest arose around Mesenchymal Stem Cells (MSCs) - based therapies for one-step clinical applications. In order to achieve a better cell targeting at the injury site, these applications would need a specific cell delivery system. Hence, in this study a protocol for an efficient cell delivery based on the rapid cell adhesion on the surface of lyophilized fibroin-coated alginate microcarriers (L-FAMs) was optimized by the Design of Experiment (DoE) method in accordance with the minimum requirements for one-step clinical application. Specific parameters (seeding time, intermittent or not dynamic culture, stirring speed and volume of cell suspension) were combined in 13 different protocols, tested on human Adipose derived stem cells - ASCs (n=3). Cell adhesion rate in term of DNA quantification and metabolic activity of cells adhered on L-FAMs, and their qualitative observations by Calcein Staining were evaluated. The data showed that a suspension of 3.75 × 10. 5. cells/ml and 10 mg/ml of FAMs, 12.3 rpm of stirring speed and 85.6 minutes of seeding time are the most performing combination of parameters. The final protocol was then tested and validated on both hASCs (n=3) and human
Intervertebral disc (IVD) degeneration presents a harsh microenvironment characterised by low glucose, low oxygen and matrix acidity posing a significant challenge for cell-based therapies. The objective of this work was to assess the effect of primed
INTRODUCTION. The generation of cartilage from progenitor cells for the purpose of cartilage repair is often hampered by unwanted ossification of the generated tissue due to endochondral ossification. Our in vitro data show that celecoxib is able to suppress the hypertrophic differentiation phase of endochondral ossification in differentiating human
Summary. Indomethacin has differential effects on chondrogencic outcome depending on differentiation stage. Introduction. Heterotopic ossification (HO) is the abnormal formation of bone in soft tissues and is a frequent complication of hip replacement surgery. The standard treatment to prevent HO is administration of the NSAID indomethacin. HOs are described to develop via endochondral ossification. As it is currently unknown how indomethacin prevents HO, we aimed to define whether indomethacin might influence HO via impairing the chondrogenic phase of endochondral ossification. Materials. ATDC5, human
Summary Statement. Preoperative bone-marrow-derived cell mobilization by G-CSF is a safe orthopaedic procedure and allows circulation in the blood of high numbers of CD34+ve cells, promoting osseointegration of a bone substitute. Introduction. Granulocyte-colony-stimulating-factor(G-CSF) has been used to improve repair processes in different clinical settings for its role in bone-marrow stem cell(CD34+ and CD34-) mobilization. Recent literature suggests that G-CSF may also play a role in skeletal-tissue repair processes. Aim of the study was to verify the feasibility and safety of preoperative bone-marrow cell (BMC) mobilization by G-CSF in orthopaedic patients and to evaluate G-CSF efficacy in accelerating bone regeneration following opening-wedge high tibial valgus osteotomy(HTVO) for genu varum. Patients/Methods. 24 patients were enrolled in a prospective phase II trial. The osteotomy gap was filled by a hydroxyapatite-tricalciumphosphate bone substitute(HATriC). Patients were randomised to receive (GROUP A) or not receive (GROUP B) preoperatively a daily dose of 10µg/kg of G-CSF for three consecutive days, with an additional dose 4 hours before surgery. BMC-mobilization was monitored by white blood cell (WBC)-count, flow-cytometry analysis of circulating CD34+cells and Colony-forming cell assays. Patients were evaluated by: Lysholm and SF-36 scores preoperatively and at 1, 2, 3, 6, and 12 months after surgery;. X-ray evaluation preoperatively and at 1, 2, 3, 6, and 12 months after surgery, in order to compare the percentage of osseointegration of the bone-graft junction using the semi-quantitative score of Dallari[1]. CT-scan of the host bone-substitute interface at 2 months, in order to estimate the quality of the newly formed bone at the bone-graft junction by a quantitative measure of bone density (by Hounsfield unit) at the proximal and distal bone-graft junctions. Results. All patients completed the treatment program without major side effects; G-CSF was well tolerated. BMC-mobilization occurred in all Group A patients, with median peak values of 110/µL (range 29–256) of circulating CD34+ve cells. Circulating clonogenic progenitors paralleled CD34+ve cell levels. A significant improvement in the SF-36-Role-Physical scale and in the Lysholm score was recorded at follow-up in Group A compared to Group B(p<0.05). At the X-ray-evaluation, there was a significant increase in osseointegration at the bone-graft junction in Group A at 1, 2, 3 and 6 months post-surgery compared to Group B(p<0.05). CT-scans of the grafted area at 2 months post-surgery showed no significant difference in the quality of the newly formed bone between the two Groups. Discussion/Conclusions. These results suggest that G-CSF can be safely administered preoperatively in subjects undergoing HTVO. In addition, the clinical, radiographic and CT monitoring indicate that preoperative G-CSF administration promotes bone graft substitute osseointegration. Enhanced osseointegration might be the result of the direct activity of G-CSF on the host bone or a cellular effect mediated by bone marrow-derived progenitors mobilised by G-CSF, or by a combination of all these factors. This study is a proof-of-principle that preoperative G-CSF might be an alternative treatment option to enhance bone regeneration in the field of
Post-natal vasculogenesis, the process by which vascular committed
Summary Statement. Umbilical cord derived stem cell secretion could enhance the osteogenic differentiation of human