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  1. Baba Ismail YM, Wimpenny I, Bretcanu O, Dalgarno K, El Haj AJ
    J Biomed Mater Res A, 2017 Jun;105(6):1775-1785.
    PMID: 28198131 DOI: 10.1002/jbm.a.36038
    Ionic substitutions have been proposed as a tool to control the functional behavior of synthetic hydroxyapatite (HA), particularly for Bone Tissue Engineering applications. The effect of simultaneous substitution of different levels of carbonate (CO3) and silicon (Si) ions in the HA lattice was investigated. Furthermore, human bone marrow-derived mesenchymal stem cells (hMSCs) were cultured on multi-substituted HA (SiCHA) to determine if biomimetic chemical compositions were osteoconductive. Of the four different compositions investigates, SiCHA-1 (0.58 wt % Si) and SiCHA-2 (0.45 wt % Si) showed missing bands for CO3and Si using FTIR analysis, indicating competition for occupation of the phosphate site in the HA lattice; 500°C was considered the most favorable calcination temperature as: (i) the powders produced possessed a similar amount of CO3(2-8 wt %) and Si (<1.0 wt %) as present in native bone; and (ii) there was a minimal loss of CO3and Si from the HA structure to the surroundings during calcination. Higher Si content in SiCHA-1 led to lower cell viability and at most hindered proliferation, but no toxicity effect occurred. While, lower Si content in SiCHA-2 showed the highest ALP/DNA ratio after 21 days culture with hMSCs, indicating that the powder may stimulate osteogenic behavior to a greater extent than other powders. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1775-1785, 2017.
  2. Baba Ismail YM, Ferreira AM, Bretcanu O, Dalgarno K, El Haj AJ
    Colloids Surf B Biointerfaces, 2017 Nov 01;159:445-453.
    PMID: 28837894 DOI: 10.1016/j.colsurfb.2017.07.086
    This paper presents a new approach in assembling bone extracellular matrix components onto PLA films, and investigates the most favourable environment which can be created using the technique for cell-material interactions. Poly (lactic acid) (PLA) films were chemically modified by covalently binding the poly(ethylene imine) (PEI) as to prepare the substrate for immobilization of polyelectrolyte multilayers (PEMs) coating. Negatively charged polyelectrolyte consists of well-dispersed silicon-carbonated hydroxyapatite (SiCHA) nanopowders in hyaluronic acid (Hya) was deposited onto the modified PLA films followed by SiCHA in collagen type I as the positively charged polyelectrolyte. The outermost layer was finally cross-linked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrocholoride and N-hydroxysulfosuccinimide sodium salt (EDC/NHS) solutions. The physicochemical features of the coated PLA films were monitored via X-ray Photoelectron Spectroscopy (XPS) and Atomic Force Microscope (AFM). The amounts of calcium and collagen deposited on the surface were qualitatively and quantitatively determined. The surface characterizations suggested that 5-BL has the optimum surface roughness and highest amounts of calcium and collagen depositions among tested films. In vitro human mesenchymal stem cells (hMSCs) cultured on the coated PLA films confirmed that the coating materials greatly improved cell attachment and survival compared to unmodified PLA films. The cell viability, cell proliferation and Alkaline Phosphatase (ALP) expression on 5-BL were found to be the most favourable of the tested films. Hence, this newly developed coating materials assembly could contribute to the improvement of the bioactivity of polymeric materials and structures aimed to bone tissue engineering applications.
  3. Law JX, Musa F, Ruszymah BH, El Haj AJ, Yang Y
    Med Eng Phys, 2016 Sep;38(9):854-61.
    PMID: 27349492 DOI: 10.1016/j.medengphy.2016.05.017
    Collagen and fibrin are widely used in tissue engineering due to their excellent biocompatibility and bioactivities that support in vivo tissue formation. These two hydrogels naturally present in different wound healing stages with different regulatory effects on cells, and both of them are mechanically weak in the reconstructed hydrogels. We conducted a comparative study by the growth of rat dermal fibroblasts or dermal fibroblasts and epidermal keratinocytes together in collagen and fibrin constructs respectively with and without the reinforcement of electrospun poly(lactic acid) nanofiber mesh. Cell proliferation, gel contraction and elastic modulus of the constructs were measured on the same gels at multiple time points during the 22 day culturing period using multiple non-destructive techniques. The results demonstrated considerably different cellular activities within the two types of constructs. Co-culturing keratinocytes with fibroblasts in the collagen constructs reduced the fibroblast proliferation, collagen contraction and mechanical strength at late culture point regardless of the presence of nanofibers. Co-culturing keratinocytes with fibroblasts in the fibrin constructs promoted fibroblast proliferation but exerted no influence on fibrin contraction and mechanical strength. The presence of nanofibers in the collagen and fibrin constructs played a favorable role on the fibroblast proliferation when keratinocytes were absent. Thus, this study exhibited new evidence of the strong cross-talk between keratinocytes and fibroblasts, which can be used to control fibroblast proliferation and construct contraction. This cross-talk activity is extracellular matrix-dependent in terms of the fibrous network morphology, density and strength.
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