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    ABSTRACT: Musculoskeletal reconstructive surgery often requires removal of significant quantities of bone tissue, such as the periosteum, causing critical problems following surgery like friction between different tissues and adhesion of soft tissues to the underlying bone. We studied the long-term host response and closure of large bone defects for periosteal reconstruction using Hyalonect, a novel membrane comprising knitted fibers of esterified hyaluronan, (HYAFF11). For biological characterization, 162 rats were used in a defect model in which a section of the dorsal muscular fascia was removed, and the membrane behavior observed over 540 d using conventional histology, with sham operated rats as controls. In addition, Hyalonect was used to cover defects made in the humeri of 7 dogs, filled with a variety of conventional bone filling compounds, and the regeneration process observed after 6 wks using histology. Low levels of inflammation were observed in the dorsal muscle fascia defect model, with cellular colonization of the mesh by 30 d, vascularization by 120 days, matrix fiber organization by 270 d, and the appearance of connective tissue identical to the surrounding tissue between 365 and 540 d, without the formation of fibrotic tissue. In addition, Hyalonect was shown to allow the regeneration of bone within the humeral defects whilst preventing fibrotic tissue in-growth, and allowing regeneration of tissue which, by 6 wk, had begun to resemble natural periosteal tissue. Hyalonect is suitable for improving the outcome of the final phases of orthopedic and trauma reconstructive surgical procedures, especially in the reconstruction of periosteal tissue.
    No preview · Article · Oct 2010 · Journal of Surgical Research
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    ABSTRACT: A range of poly epsilon-caprolactone (PCL) films mixed/doped with poly(lactide-co-glycolide) (PLGA) (65:35) in 0, 10, 20, and 30 wt % were produced, sterilized using ethylene oxide, and analyzed using FTIR. Characterized human mesenchymal stem cells (hMSCs) were cultured in contact with the materials in basal, chondrogenic, and osteogenic medium for time periods up to 28 days, to determine if the materials could induce differentiation of MSC both in the presence and absence of biological stimuli. Viable cell adhesion was analyzed under all conditions. Collagen I, collagen II, sox-9, osteocalcin, osteopontin, osteonectin, and CBFA1 were evaluated at both the mRNA (real-time PCR) and protein production levels (fluorescent immunohistochemistry) and used to identify cell differentiation. Pure PCL and PCL mixed with PLGA demonstrated a chondrogenic potential. Only PCL 8 (80 wt % PCL, 20 wt % PLGA) facilitated osteogenic differentiation of MSCs under osteogenic conditions. This was attributed to the increased hydrophilic nature of the surface allowing sufficient homogeneous cell attachment and the formation of filamentous F-actin in the cells, allowing osteogenic differentiation. Of all materials tested, PCL 7 (70 wt % PCL, 30 wt % PLGA) demonstrated the greatest chondrogenic differentiation potential under basal and stimulated conditions at both the mRNA and protein production level.
    No preview · Article · Apr 2009 · Journal of Biomedical Materials Research Part A
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    ABSTRACT: Scaffolds with 400 microm pores constructed from hyaluronan modified by benzyl esterification of the carboxylic acid groups (HYAFF-11) and viscous gels created from dodecyl-amidation of hyaluronan (HYADD-3) were implanted subcutaneously into rats for periods of up to 26 and 12 weeks, respectively. Tissue explants were infiltrated with methacrylate resin, sectioned and stained with a broad panel of inflammatory markers in addition to conventional histological stains. Both gels and sponges became rapidly infiltrated by cells that, in the case of HYAFF sponges, did not differentiate, whilst mature adipocytes were only observed at the margins of the sponges. This was combined with sustained inflammatory antigen expression. Conversely, in the HYADD gels, only moderate inflammatory staining was observed at 4 weeks which had diminished completely by 8 weeks. Mature and maturing adipocytes were observed deep within the gels. It is hypothesised that the gels present an excellent inflammatory cytokine profile which induces macrophage infiltration, proliferation then differentiation into adipocytes and is responsible for the generation of neoadipogenesis.
    Preview · Article · Jan 2008 · Biomaterials
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