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Composite sandwich panels are manufactured by gluing plywood skins to either bamboo rings to produce Bamboo Core Sandwich (BCS) panels or peeler core rings to produce Peeler Core Sandwich (PCS) panels. Both single- and double-layer panels are produced. The manufactured panels are tested under four-point bending and three-point shear tests. Results are compared to the test results of conventional Cross-laminated Timber (CLT) panels. Moreover, one single-layer PCS panel with thicker plywood skins and less peeler core rings (PCS-TH) is manufactured. No significant improvements are observed in the double-layer panels compared to the single-layer panels in bending. However, in shear, double-layer panels show more consists capacities. The results indicate that the proposed PCS panel displays better ductile performance in bending and shear compared to CLT, suggesting it could be a preferred product choice in some building applications. Reduced weight, lower material costs, ease of manufacturing and usage of sustainable/waste products, make the proposed sandwich panels a potential alternative for CLT in terms of structural performance.

OBJECTIVE: Endometriosis is a common and painful condition characterised by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of endometriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial menstruation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy. RESULT(S): Treatment with 5E1 reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis.

HYPOTHESIS/AIMS OF STUDY: Until recently, polypropylene meshes were often used as a surgical treatment option for Pelvic Organ Prolapse (POP). However, they have been associated with serious complications such as infammation, pain and erosion. As a result, transvaginal meshes were banned in Australia and New Zealand in 2017. At present, there is no optimal therapy for treatment of chronic POP leaving millions of women in despair. To overcome adverse events associated with trans-vaginal surgery using non degradable synthetic mesh for treating pelvic organ prolapse (POP), we are developing a tissue engineering construct comprising degradable nano-fbrous mesh and endometrial mesenchymal stem/stromal cells (eMSC). The aim of this study was to investigate in vivo foreign body response, angiogenesis and extracellular matrix gene expression to a nano-topographically controlled mesh made of poly (L-lactic acid)-co-poly(-caprolactone) and gelatin incorporating eMSC (PLCL/G/eMSC). Our team discovered a rare population of Mesenchymal stem cells in the endometrium (eMSCs) and has identifed a single marker to isolate these rare perivascular cells. In a phase IV clinical trial, our team has also showed that eMSCs can be collected with ease even from post-menopausal women and kept in an undiferentiated state for clinical use making them an ideal choice for autologous urogynecological application. We further more compared the diferences between the treatment capacity of eMSCs delivered using degradable and non-degradable. STUDY DESIGN, MATERIALS AND METHODS: PLCL polymer and gelatin (1:1, 10%w/w) was electrospun to form uniform nanofbers and assessed for fbre diameter, pore size, hydrophilicity and biomechanical properties. SUSD2+ eMSC were purifed from single cell suspensions obtained from endometrial biopsies from cycling women and by magnetic bead sorting and transfected with mCherry len-tivirus for cell tracking. SEM was used to characterise eMSC incorporation into the nanofber

Introduction: To overcome adverse events associated with transvaginal surgery using non degradable synthetic mesh for treating pelvic organ prolapse (POP), we are developing a tissue engineering construct comprising degradable nanofibrous mesh and endometrial mesenchymal stem/stromal cells (eMSC). The aim of this study was to investigate the in vitro cell-material properties and in vivo foreign body response to a nano-topographically controlled mesh made of poly (L-lactic acid)-copoly( -caprolactone) and gelatin incorporating eMSC (PLCL/G/eMSC). Method(s): PLCL alone and a 1:1 blend with gelatin (w/w) were electrospun from a 10% solution at 1 ml/hr and 18kV over 12.5 cm to form uniform nanofibers and assessed for fibre diameter, pore size, hydrophilicity and biomechanical properties. SUSD2+ eMSC were purified from single cell suspensions obtained from endometrial biopsies from cycling women by magnetic bead sorting and transfected with mCherry lentivirus for cell tracking. SEM was used to characterise eMSC incorporation into the PLCL and PLCL/G nanofiber meshes in vitro and their degradation in NSG mouse skin wound repair model of vaginal repair (2, 6 wks, 4 mice/gp). IF and confocal microscopy was used to assess total (F4/80+), M1 (F4/80+CCR7+) and M2 (F4/80+/CD206+) macrophages. Result(s): Addition of G to PLCL increased fiber size 40% (P<0.05) and pore size 25% (P<0.05) rendering meshes hydrophilic without change in tensile properties. In vitro, eMSC rapidly adhered, penetrated, incorporated and proliferated (P<0.01) in PLCL/G mesh with a 2.5 fold greater coverage than PLCL alone (P<0.05). In vivo, mCherry+ eMSC survived 1 wk in PLCL and PLCL/G implanted mesh, but only a few were retained in PLCL/G and none in PLCL at 6 wk. eMSC prevented PLCL/G nanofiber degradation 2 fold (P <0.0001) and increased cellular infiltration into the mesh 1.5 fold (P<0.05) at 6 wks. eMSC seeded on PLCL/G promoted macrophage switching from M1 to M2 phenotype to a greater extent than s

The widespread use of synthetic transvaginal polypropylene mesh for treating Pelvic Organ Prolapse (POP) has been curtailed due to serious adverse effects highlighted in 2008 and 2011 FDA warnings and subsequent legal action. We are developing new synthetic mesh to deliver endometrial mesenchymal stem cells (eMSC) to improve mesh biocompatibility and restore strength to prolapsed vaginal tissue. Here we evaluated knitted polyamide (PA) mesh in an ovine multiparous model using transvaginal implantation and matched for the degree of POP. Polyamide mesh dip-coated in gelatin and stabilised with 0.5% glutaraldehyde (PA/G) were used either alone or seeded with autologous ovine eMSC (eMSC/PA/G), which resulted in substantial mesh folding, poor tissue integration and 42% mesh exposure in the ovine model. In contrast, a two-step insertion protocol, whereby the uncoated PA mesh was inserted transvaginally followed by application of autologous eMSC in a gelatin hydrogel onto the mesh and crosslinked with blue light (PA + eMSC/G), integrated well with little folding and no mesh exposure. The autologous ovine eMSC survived 30 days in vivo but had no effect on mesh integration. The stiff PA/G constructs provoked greater myofibroblast and inflammatory responses in the vaginal wall, disrupted the muscularis layer and reduced elastin fibres compared to PA + eMSC/G constructs. This study identified the superiority of a two-step protocol for implanting synthetic mesh in cellular compatible composite constructs and simpler surgical application, providing additional translational value.Copyright © 2019 Elsevier Ltd

Endometrial mesenchymal stem/stromal cells (eMSCs) exhibit excellent regenerative capacity in the endometrial lining of the uterus following menstruation and high proliferative capacity in vitro. Bioprinting eMSCs onto a mesh could be a potential therapy for Pelvic Organ Prolapse (POP). This study reports an alternative treatment strategy targeting vaginal wall repair using bioprinting of eMSCs encapsulated in a hydrogel and 3D melt electrospun mesh to generate a tissue engineering construct. Following a CAD, 3D printed poly epsilon-caprolactone (PCL) meshes were fabricated using melt electrospinning (MES) at different temperatures using a GMP clinical grade GESIM Bioscaffolder. Electron and atomic force microscopies revealed that MES meshes fabricated at 100 degreeC and with a speed 20 mm/s had the largest open pore diameter (47.2 +/- 11.4 mum) and the lowest strand thickness (121.4 +/- 46 mum) that promoted optimal eMSC attachment. An Aloe Vera-Sodium Alginate (AV-ALG) composite based hydrogel was optimised to a 1:1 mixture (1%AV-1%ALG) and eMSCs, purified from human endometrial biopsies, were then bioprinted in this hydrogel onto the MES printed meshes. Acute in vivo foreign body response assessment in NSG mice revealed that eMSC printed on MES constructs promoted tissue integration, eMSC retention and an anti-inflammatory M2 macrophage phenotype characterised by F4/80+CD206+ colocalization. Our results address an unmet medical need highlighting the potential of 3D bioprinted eMSC-MES meshes as an alternative approach to overcome the current challenges with non-degradable knitted meshes in POP treatment. Statement of Significance: This study presents the first report of bioprinting mesenchymal stem cells derived from woman endometrium (eMSCs) to boost Pelvic Organ Prolapse (POP) treatment. It impacts over 50% of elderly women with no optimal treatment at present. The overall study is conducted in three stages as fabricating a melt electrospun (MES) mesh, bioprint

The current urogynecological clinical meshes trigger unfavorable foreign body response which leads to graft failure in the long term. To overcome the present challenge, we applied a tissue engineering strategy using endometrial SUSD2+ mesenchymal stem cells (eMSCs) with high regenerative properties. This study delves deeper into foreign body response to SUSD2+ eMSC based degradable PLACL/gelatin nanofiber meshes using a mouse model targeted at understanding immunomodulation and mesh integration in the long term. Delivery of cells with nanofiber mesh provides a unique topography that enables entrapment of therapeutic cells for up to 6 weeks that promotes substantial cellular infiltration of host anti-inflammatory macrophages. As a result, degradation rate and tissue integration are highly impacted by eMSCs, revealing an unexpected level of implant integration over 6 weeks in vivo. From a clinical perspective, such immunomodulation may aid in overcoming the current challenges and provide an alternative to an unmet women's urogynecological health need.Copyright © 2018 American Chemical Society.

The flexural stiffness and ultimate load capacity of novel ultralight composite sandwich panels, made of plywood faces and bamboo or peeling cores are investigated herein. Modified Ritz method and sandwich beam theory formulations for composite sandwich panels with thick faces and thick/stiff cores are developed, and are used to find the bending stiffness of the panels in one-way and two-way bending. The ultimate capacity and failure modes of the panels are then predicted from nonlinear material and geometric finite element analyses (FEA). The numerical methods are validated against published experimental results of orthotropic composite sandwich panels. It is shown that at similar panel depths, the proposed composite timber panels can be as high as 15% stiffer and 40% lighter than the existing commercial cross-laminated timber (CLT) panels. Results of a parametric study on selected composite panels with different yield stresses in compression, show that panels with bamboo cores exhibit relatively more ductile behaviour compared to those with peeling cores. At the ultimate flexural capacity, the tensile face of the panels fails in tension parallel to the grain, while the compressive face almost reaches its yield capacity. © 2018

Introduction: Non-degradable synthetic mesh for treating pelvic organ prolapse (POP) have been banned many countries due to the adverse events associated with transvaginal surgery. There is more focus on use of degradable materials as an alternative approach. Irrespective of the material choice, all implants elicit a foreign body response (FBR). It is crucial that this response leads to an overall healing response to ensure success of the implanted graft.We recently reported the design of degradable poly (L-lactic acid)-co-poly(-caprolactone) nanofibrous mesh (PLCL) bioengineered with endometrial mesenchymal stem/stromal cells (eMSC) for POP repair. Objective(s): The aim of this study was to extend our knowledge and investigate the key players that enable this eMSCs based foreign body response modulation following PLCL nanomesh implantation. Furthermore, we wanted to explore, the feasibility and fate of using them as vaginal implants in a large animal model of POP. Method(s): PLCL was electrospun from a 10% (w/w) polymer solution at 1 ml/hr and 18kV over 12.5 cm to form uniform nanofibers. SUSD2+ eMSC were purified from single cell suspensions obtained from endometrial biopsies (n=7) from cycling women by magnetic bead sorting. For gene expression study, PLCL with and without eMSCs were implanted under NSG mouse skin (1, 6 wks, 7 mice/gp/time-point). Quantitative PCR was used to assess 50 genes associated with extracellular matrix (ECM), cell adhesion, angiogenesis and inflammation as fold changes compared to sham. For evaluation as vaginal performance, implants were transvaginal sutured in our parous sheep model for POP. Immunohistochemistry and electron microscopy were used to visualize new ECM and blood vessels around implants. Result(s): In our mice model, PLCL with eMSCs with significantly increased (P<0.05) ECM genes such as Col1a1 (3 folds), Col3a1(3 folds), Col6a1(2 folds), Col6a2 (1.8 folds) at 6 weeks. There was also a significant increase (P<0.05) inECMre

HYPOTHESIS / AIMS OF STUDY Pelvic organ prolapse (POP) is common urogynecological disorder, with up to 19% of women having a lifetime risk of undergoing reconstructive surgery for POP [1], and a 30% risk of reoperation due to recurrent anatomical failure or adverse events associated with primary surgery [2]. There is a critical need to provide novel meshes for the treatment of POP that are safe, surgically efficacious, and congruent with host native tissue. Cellular therapy is an emerging field in clinical and personalised medicine that utilizes the clonogenic potential of adult mesenchymal stem/stromal cells to improve the biocompatibility of novel surgical constructs, which has potential applications in POP. Our discovery of endometrial stem/progenitor cells (eMSC) within unique perivascular niches of endometrial functionalis tissue has furthered the field of stem cell therapy, due to their improved clonogenicity and potential to modulate the foreign body responses triggered by meshes. In nature, cell behaviour and structural development is supported by the nanoscale arrangement of the extracellular matrix (ECM). In order to overcome the impediment posed by the tissue microenvironment, it is desirable to design biomaterials that mimic some mechanical and biochemical properties of the ECM of native tissues. Nanostructured poly-L-lactide-co--caprolactone (PLCL) mesh is made from a biocompatible, elastic and flexible polymer that is well matched to the nanoarchitecture of vaginal tissue [3]. In a previous study on mice, PLCL mesh blended with eMSC resulted in improved tissue integration, host cell recruitment, neovascularisation and ECM deposition, when compared with PLCL mesh alone [3]. Objective(s): This study aimed to assess the fate and effect of nanofiber PLCL mesh boosted with SUSD2+ eMSC in an ovine pre-clinical model of POP surgery (n=42). We hypothesised that when combined with eMSC, this degradable nanofiber construct strengthens the vaginal wall, whilst im

Introduction: Non-degradable synthetic mesh for treating pelvic organ prolapse (POP) have been banned many countries due to the adverse events associated with transvaginal surgery. There is more focus on use of degradable materials as an alternative approach. Irrespective of the material choice, all implants elicit a foreign body response (FBR). It is crucial that this response leads to an overall healing response to ensure success of the implanted graft.We recently reported the design of degradable poly (L-lactic acid)-co-poly(-caprolactone) nanofibrous mesh (PLCL) bioengineered with endometrial mesenchymal stem/stromal cells (eMSC) for POP repair. Objective(s): The aim of this study was to extend our knowledge and investigate the key players that enable this eMSCs based foreign body response modulation following PLCL nanomesh implantation. Furthermore, we wanted to explore, the feasibility and fate of using them as vaginal implants in a large animal model of POP. Method(s): PLCL was electrospun from a 10% (w/w) polymer solution at 1 ml/hr and 18kV over 12.5 cm to form uniform nanofibers. SUSD2+ eMSC were purified from single cell suspensions obtained from endometrial biopsies (n=7) from cycling women by magnetic bead sorting. For gene expression study, PLCL with and without eMSCs were implanted under NSG mouse skin (1, 6 wks, 7 mice/gp/time-point). Quantitative PCR was used to assess 50 genes associated with extracellular matrix (ECM), cell adhesion, angiogenesis and inflammation as fold changes compared to sham. For evaluation as vaginal performance, implants were transvaginal sutured in our parous sheep model for POP. Immunohistochemistry and electron microscopy were used to visualize new ECM and blood vessels around implants. Result(s): In our mice model, PLCL with eMSCs with significantly increased (P<0.05) ECM genes such as Col1a1 (3 folds), Col3a1(3 folds), Col6a1(2 folds), Col6a2 (1.8 folds) at 6 weeks. There was also a significant increase (P<0.05) inECMre

HYPOTHESIS / AIMS OF STUDY Pelvic organ prolapse (POP) is common urogynecological disorder, with up to 19% of women having a lifetime risk of undergoing reconstructive surgery for POP [1], and a 30% risk of reoperation due to recurrent anatomical failure or adverse events associated with primary surgery [2]. There is a critical need to provide novel meshes for the treatment of POP that are safe, surgically efficacious, and congruent with host native tissue. Cellular therapy is an emerging field in clinical and personalised medicine that utilizes the clonogenic potential of adult mesenchymal stem/stromal cells to improve the biocompatibility of novel surgical constructs, which has potential applications in POP. Our discovery of endometrial stem/progenitor cells (eMSC) within unique perivascular niches of endometrial functionalis tissue has furthered the field of stem cell therapy, due to their improved clonogenicity and potential to modulate the foreign body responses triggered by meshes. In nature, cell behaviour and structural development is supported by the nanoscale arrangement of the extracellular matrix (ECM). In order to overcome the impediment posed by the tissue microenvironment, it is desirable to design biomaterials that mimic some mechanical and biochemical properties of the ECM of native tissues. Nanostructured poly-L-lactide-co--caprolactone (PLCL) mesh is made from a biocompatible, elastic and flexible polymer that is well matched to the nanoarchitecture of vaginal tissue [3]. In a previous study on mice, PLCL mesh blended with eMSC resulted in improved tissue integration, host cell recruitment, neovascularisation and ECM deposition, when compared with PLCL mesh alone [3]. Objective(s): This study aimed to assess the fate and effect of nanofiber PLCL mesh boosted with SUSD2+ eMSC in an ovine pre-clinical model of POP surgery (n=42). We hypothesised that when combined with eMSC, this degradable nanofiber construct strengthens the vaginal wall, whilst im