Bio-Medical Materials and Engineering - Volume 28, issue s1
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Bio-Medical Materials and Engineering is to promote the welfare of humans and to help them keep healthy. This international journal is an interdisciplinary journal that publishes original research papers, review articles and brief notes on materials and engineering for biological and medical systems.
Articles in this peer-reviewed journal cover a wide range of topics, including, but not limited to: Engineering as applied to improving diagnosis, therapy, and prevention of disease and injury, and better substitutes for damaged or disabled human organs; Studies of biomaterial interactions with the human body, bio-compatibility, interfacial and interaction problems; Biomechanical behavior under biological and/or medical conditions; Mechanical and biological properties of membrane biomaterials; Cellular and tissue engineering, physiological, biophysical, biochemical bioengineering aspects; Implant failure fields and degradation of implants. Biomimetics engineering and materials including system analysis as supporter for aged people and as rehabilitation; Bioengineering and materials technology as applied to the decontamination against environmental problems; Biosensors, bioreactors, bioprocess instrumentation and control system; Application to food engineering; Standardization problems on biomaterials and related products; Assessment of reliability and safety of biomedical materials and man-machine systems; and Product liability of biomaterials and related products.
Abstract: Stem cell-based therapies have been recently investigated in the field of organic erectile dysfunctions, such as those associated with diabetes or the treatment of prostate cancer. The overall aim is to repair the repair the underlying penile cellular damage. Here, we review the rationale behind the use of stem cells injection in post-radical prostatectomy erectile dysfunction (pRP-ED). Radical prostatectomy for prostate cancer induces complex neurologic and vascular injuries that cause one of the most difficult-to-treat forms of erectile dysfunction. Evidence from animal models replicating pRP-ED suggests that intracavernous injection of autologous bone marrow mononuclear cells (BM-MNCs) may represent the…first curative approach. Several clinical trials are ongoing and two of them have been completed with encouraging results.
Keywords: Erectile dysfunction, radical prostatectomy, bone marrow, cavernous nerves
Abstract: The construction of the high biocompatible biomaterials pretreated with MSC offers a promising strategy to improve the effects of stem cell therapy for the myocardial infarction (MI). However, assembling vascularized three-dimensional (3-D) myocardial tissues remains an enormous challenge. In this study, we optimized the decellularization protocol with the umbilical artery to construct microporous 3-D scaffold which is suitable for the stem cells (SC) proliferation. The SD rats underwent proximal left coronary ligation and a 5-mm diameter microporous SC patch was implanted directly on the infarct area (SC patch group). The LV contractile function, regional myocardial wall compliance, and tissue histology…were assessed 4 weeks after patch implantation. The MSC patch integrated to the local heart tissue and the neo-vessels have been observed in the MSC patch. The vessels in the MSC patch were positive for the CD31 (marker for the mature endothelial cells). The left ventricle wall was thicker in the MSC patch group than the control group (p < 0.05 vs. empty patch group). And the LVEF has been improved in the MSC patch group than empty patch group (59 ± 6.7 % vs. 31 ± 4.5 % , p < 0.05 ). Conclusions: Our results showed that the implantation of the MSC patch improved cardiac contractile function in heart infarction rat model. The construction of artificial tissue from the decellularized umbilical artery and the MSC may open a promising perspective for the tissue therapy for MI.
Abstract: Background: Human tissue derived natural extracellular matrix (ECM) has great potential in tissue engineering. Objective: We sought to isolate extracellular matrix derived from human umbilical cord and test its potential in tissue engineering. Methods: An enzymatic method was applied to isolate and solubilized complete human umbilical cord derived matrix (hUCM). The obtained solution was analyzed for growth factors, collagen and residual DNA contents, then used to coat 2D and 3D surfaces for cell culture application. Results: The hUCM was successfully isolated with trypsin digestion to acquire a solution containing various growth factors and collagen…but no residual DNA. This hUCM solution can form a coating on 2D and 3D substrates suitable cell culture. Conclusion: We developed a new matrix derived from human source that can be further used in tissue engineering.
Abstract: Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are widely used in tissue engineering. In vascular engineering, the ability to obtain a vessel replacement with contractile smooth muscle cells (SMC) is a key factor. In this work, we demonstrated that WJ-MSCs differentiate towards a SMC phenotype with various stimulations in vitro and that the modification of redox state could be involved. WJ-MSCs were isolated from umbilical cords. After their expansion, the cells were stimulated with ascorbic acid (AA, 300 μ M) or transforming growth factor (TGF)-β 1 (1 to 5 ng/mL). SMC markers were analyzed by Western blot.…Modification of redox state was evaluated by reactive oxygen species (ROS) production and glutathione (GSH) content measurements. TGF-β 1 or AA-stimulated WJ-MSCs express early and intermediate SMC markers. TGF-β 1 (5 ng/mL) modifies the redox state by a ROS production and a GSH content drop, while AA has no effect. This work showed that TGF-β 1 and AA are effective SMC phenotype inducers to differentiate WJ-MSCs.
Abstract: Mini-invasive surgery restricts the surgeon information to two-dimensional digital representation without the corresponding physical information obtained in previous open surgery. To overcome these drawbacks, real time augmented reality interfaces including the true mechanical behaviour of organs depending on their internal microstructure need to be developed. For the case of tumour resection, we present here a finite element numerical study of the liver mechanical behaviour including the effects of its own vascularisation through numerical indentation tests in order extract the corresponding macroscopic behaviour. The obtained numerical results show excellent correlation of the corresponding force-displacement curves when compared with macroscopic experimental data…available in the literature.
Keywords: Liver, vascularisation, finite element model, numerical simulation, indentation tests, real time
Abstract: Liver transplantation is the definitive treatment for patients with end-stage liver diseases (ESLD). However, it is hampered by shortage of liver donor. Liver tissue engineering, aiming at fabricating new livers in vitro , provides a potential resolution for donor shortage. Three elements need to be considered in liver tissue engineering: seeding cell resources, scaffolds and bioreactors. Studies have shown potential cell sources as hepatocytes, hepatic cell line, mesenchymal stem cells and others. They need scaffolds with perfect biocompatiblity, suitable micro-structure and appropriate degradation rate, which are essential charateristics for cell attachment, proliferation and secretion in forming extracellular matrix. The most…promising scaffolds in research include decellularized whole liver, collagens and biocompatible plastic. The development and function of cells in scaffold need a microenvironment which can provide them with oxygen, nutrition, growth factors, et al. Bioreactor is expected to fulfill these requirements by mimicking the living condition in vivo . Although there is great progress in these three domains, a large gap stays still between their researches and applications. Herein, we summarized the recent development in these three major fields which are indispensable in liver tissue engineering.
Abstract: The relevance of research on reconstructed organs is justified by the lack of organs available for transplant and the growing needs for the ageing population. The development of a reconstructed organ involves two parallel complementary steps: de-cellularization of the organ with the need to maintain the structural integrity of the extracellular matrix and vascular network and re-cellularization of the scaffold with stem cells or resident cells. Whole organ engineering for liver, heart, lung or kidneys, is particularly difficult because of the structural complexity of organs and heterogeneity of cells. Rodent, porcine and rhesus monkey organs have been de-cellularized to…obtain a scaffold with preserved extracellular matrix and vascular network. As concern the cells for re-cellularization, embryonic, foetal, adult, progenitor stem cells and also iPS have been proposed. Heart construction could be an alternative option for the treatment of cardiac insufficiency. It is based on the use of an extra-cellular matrix coming from an animal’s heart and seeded with cells likely to reconstruct a normal cardiac function. Though de-cellularization techniques now seem controlled, the issues posed by the selection of cells capable of generating the various components of cardiac tissue are not settled yet. In addition, the recolonisation of the matrix does not only depend on the phenotype of cells that are used, but it is also impacted by the nature of biochemical signals emitted. Recent researches have shown that it is possible to use decellularized whole liver treated by detergents as scaffold, which keeps the entire network of blood vessels and the integrated extracellular matrix (ECM). Beside of decellularized whole organ scaffold seeding cells selected to repopulate a decellularized liver scaffold are critical for the function of the bioengineered liver. At present, potential cell sources are hepatocyte, and mesenchymal stem cells. Pulmonary regeneration using engineering approaches is complex. In fact, several types of local progenitor cells that contribute to cell repair have been described at different levels of the respiratory tract. Moving towards the alveoles, one finds bronchioalveolar stem cells as well as epithelial cells and pneumocytes. A promising option to increase the donor organ pool is to use allogeneic or xenogeneic decellularized lungs as a scaffold to engineer functional lung tissue ex vivo . The kidney is certainly one of the most difficult organs to reconstruct due to its complex nature and the heterogeneous nature of the cells. There is relatively little research on auto-construction, and experiments have been performed on rats, pigs and monkeys. Nevertheless, before these therapeutic approaches can be applied in clinical practice, many researches are necessary to understand and in particular the behaviour of cells on the decellularized organs as well as the mechanisms of their interaction with the microenvironment. Current knowledges allow optimism for the future but definitive answers can only be given after long term animal studies and controlled clinical studies.
Keywords: Organ reconstruction, decellularization, matrix integrity, stem cells
Abstract: Background: Mesenchymal stem cells (MSC) have been shown to have potent immunoregulatory effects. They are able to mitigate inflammation in many contexts of immune disorders, including autoimmune diseases and graft-versus-host disease (GVHD). Endotoxemia can induce systematic inflammation in the body. In this study, we try to investigate whether MSC can attenuate inflammation in models of LPS-induced endotoxemia. Methods: Bone marrow MSC (BMSC) were isolated and expanded from rats of 4~6-week age. Adult mice were divided randomly into Control group, Model group and BMSC group. LPS were injected peritoneally into mice of Model group and BMSC group to induce…endotoxemia. For BMSC group mice, 1 × 10 6 BMSC were injected through tail vein 1 hour after LPS application. Animals were sacrificed after 24 hours. Inflammatory damage in lungs and livers were detected through histochemistry. Wet/dry ratio of lung tissues was calculated, levels of inflammatory factors as IL-1β and TNF-α in lung tissues were measured through ELISA. Results: Inflammatory pathological changes in lung and liver in BMSC group were comparable to those in Model group. Moreover, in some animals, the injuries were exacerbated after BMSC treatment. Accordingly, wet/dry ratio of lung in BMSC group mice was higher than that in Model group mice. IL-1β level in BMSC-treated group mice was significantly augmented, however, no significant changes were detected between these two groups for level of TNF-α . Conclusion: Our results showed that application of BMSC in LPS-induced endotoxemia models couldn’t attenuate the inflammatory injuries in tissues. Although BMSC have been shown to be able to induce immune inhibition, however, in some instances, their immuno-inhibitory function might be regulated by the local environment.
Abstract: Febrile seizures (FS) are the most common seizure disorders in children aged 6 months to 5 years. Children suffering from complex FS have a high risk of developing subsequent temporal lobe epilepsy (TLE). Neuroinflammation is involved in the pathogenesis of FS although the mechanism remains unknown. Our previous study using the Whole Rat Genome Oligo Microarray determined that Dipeptidyl peptidase IV (DPP4 ) is potentially a related gene in FS rats. In this study, we demonstrated that DPP4 expression was significantly increased at both the protein and mRNA levels after hyperthermia induction. Sitagliptin, a specific enzyme inhibitor of DPP4,…remarkably attenuated the severity of seizures in FS rats, and hyperthermia-induced astrocytosis was suppressed after DPP4 inhibition. Furthermore, sitagliptin significantly decreased the levels of the inflammatory cytokines IL-1β , TNF-α , and IL-6 but not IL-10. In addition, sitagliptin prevented NF-κ B activation by decreasing phosphorylation of the p65 subunit. Taken together, our findings demonstrate that DPP4 functions as a critical regulator of neuroinflammation in hyperthermia-induced seizures and the DPP4 inhibitor may be a viable option for FS therapeutics.
Abstract: In this work, we present an evolutive trabecular model for bone remodeling based on a boundary detection algorithm accounting for both biology and applied mechanical forces, known to be an important factor in bone evolution. A finite element (FE) numerical model using the Abaqus/Standard® software was used with a UMAT subroutine to solve the governing coupled mechanical-biological non-linear differential equations of the bone evolution model. The simulations present cell activation on a simplified trabeculae configuration organization with trabecular thickness of 200 µ m . For this activation process, the results confirm that the trabeculae are mainly…oriented in the active direction of the principal mechanical stresses and according to the principal applied mechanical load directions. The trabeculae surface activation is clearly identified and can provide understanding of the different bone cell activations in more complex geometries and load conditions.