Osteoporosis and ageing affects the migration of stem cells and this is ameliorated by transfection with CXCR4.

OBJECTIVES: Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. METHODS: MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts. RESULTS: MSCs from OVX rats migrate significantly (p < 0.05) less towards SDF-1 (9%, sd 5%) compared with MSCs from adult (15%, sd 3%) and young rats (25%, sd 4%). Cells transfected with CXCR4 migrated significantly more towards SDF-1 compared with non-transfected cells, irrespective of whether these cells were from OVX (26.5%, sd 4%), young (47%, sd 17%) or adult (21%, sd 4%) rats. Transfected MSCs differentiated to osteoblasts express CXCR4 but do not migrate towards SDF-1. CONCLUSIONS: MSC migration is impaired by age and osteoporosis in rats, and this may be associated with a significant reduction in bone formation in osteoporotic patients. The migration of stem cells can be ameliorated by upregulating CXCR4 levels which could possibly enhance fracture healing in osteoporotic patients.Cite this article: A. Sanghani-Kerai, M. Coathup, S. Samazideh, P. Kalia, L. Di Silvio, B. Idowu, G. Blunn. Osteoporosis and ageing affects the migration of stem cells and this is ameliorated by transfection with CXCR4. Bone Joint Res 2017;6:-365. DOI: 10.1302/2046-3758.66.BJR-2016-0259.R1.

Chemical-physical and preliminary biological properties of poly (2-hydroxyethylmethacrylate)/poly-(epsilon-caprolactone)/hydroxyapa- tite composite.

In the present study, the synthesis of a semi-Interpenetrating Polymer Network (semi-IPN) incorporating linear poly-(epsilon-caprolactone) (PCL) into cross-linked poly-(2-hydroxyethylmethacrilate) (PHEMA) reinforced with hydroxyapatite (HA) has been described. The aim of this study was to improve the mechanical and biological performance of the PHEMA/PCL in the hydrated state, for orthopaedic applications. The swelling behaviour, mechanical (compressive and tensile) and surface chemical-physical (morphology, stoichiometric composition) characterisation of the novel HA reinforced composite based on PHEMA/PCL polymer matrix, PHEMA/PCL 70/30 (w/w) + 50% (w/w) HA (PHEMA/PCL/HA), were evaluated. Furthermore, a preliminary in vitro biological evaluation was also performed on the composite using a fully characterised primary human osteoblast-like (HOB) cell model. The inclusion of HA in the composite improved the mechanical performance in the swollen state, with values of elastic modulus in a similar range to that of trabecular bone. The composite surfaces showed a porous, irregular topography with the presence of: oxygen (O), carbon (C); phosphorous (P); calcium (Ca) where the Ca/P ratio was 1.78. Biological evaluation indicated undetectable weight loss of the sample, no release of toxic leachables from the composite and pH values within an acceptable range for cell growth. The results indicate that the novel PHEMA/PCL/HA composite is a promising candidate as filler or substitute for spongy bone for orthopaedic applications.

Chemical-physical characterization and in vitro preliminary biological assessment of hyaluronic acid benzyl ester-hydroxyapatite composite.

HYAFF11 is a biocompatible, biodegradable benzyl ester of hyaluronic acid. However, in order to use it for orthopedic application, its mechanical performance needs to be improved. In this study, a novel composite based on HYAFF11 polymer matrix reinforced with hydroxylapatite (HA) has been developed. Its advantage is having a similar component of the mineral phase of bone resulting in favorable osteoconductive properties. The present study has examined the compressive mechanical and surface chemical-physical properties of the novel HYAFF11-HA composite. Preliminary biological investigations, including pH and cytotoxicity studies of the material extracts, have also been performed using an in vitro primary human osteoblast-like cell model. Moreover, protein, especially fibronectin adsorption has been investigated following incubation in culture medium and human plasma. The results show a grainy surface topography composed mainly of C, P, and Ca, with a Ca/P atomic ratio indicating HA on the composite surface. Mechanical analysis shows an improvement of the compressive properties of HYAFF11 matrix, both in the dry and swollen states, with values in the range of that of spongy bone. No cytotoxic effects and no inhibition of cell proliferation have been observed in the presence of the material extracts with pH values within acceptable ranges for cell vitality. Protein studies reveal a similar pattern, but a higher amount of fibronectin following incubation in human plasma when compared with culture medium. The results show that the novel HYAFF11-HA composite shows a great potential for application in orthopedic fields, especially as vertebral trabecular bone substitute.

Scandia--a potential biomaterial?

Biocompatibility is a pre-requisite for all biomaterials used for medical application. During the last two decades significant advances have been made in the development of novel materials and selection and use of these materials has been directly dependent upon their biocompatibility. Several materials containing calcium or titanium cations demonstrate biocompatibility and are routinely used in various forms within the human body. Due to its position in the periodic table, scandium in the form of its oxide scandia (Sc(2)O(3)) was studied as the first stage of a wider exploration of the biocompatibility of ceramics. A commercial human osteoblast-like cell line (HOS TE 85) was used to study the biocompatibility of both sintered and abraded scandia surfaces. Scanning electron microscopy was used to examine cell adhesion, the MTT assay was used to measure cell metabolic function and the alamarBlue for the assessment of proliferation. Although the results are only preliminary findings, qualitative observations showed that both sintered and abraded surfaces favoured cell adhesion to the same extent. Quantitatively, a significant increase in cell proliferation was observed on Sc(2)O(3) compared to Thermanox, tissue culture control. Furthermore, Sc(2)O(3) has been shown to be non-toxic, able to be maintain cell viability and support cell growth and proliferation.