Biomatter最新文献

Endothelial plasticity, the ability of endothelial cells to alter their lineage commitment to generate other cell types, is involved in many developmental and pathological processes. It was recently shown that vascular endothelial cells are converted to a mesenchymal stem cell phenotype through a process known as endothelial-mesenchymal transition (EndMT). EndMT is characterized as a morphological and phenotypical transformation of endothelial cells that has been implicated in cardiac development, cancer, fibrosis and heterotopic ossification. Here we describe the molecular and cellular basis for EndMT-dependent generation of endothelial-derived stem cells and their potential for tissue engineering and regenerative medicine.

This study aims to provide understanding of the macroscopic viscoelastic behavior of collagen matrices through studying the relaxation time distribution spectrum obtained from stress relaxation tests. Hydrated collagen gel and dehydrated collagen thin film was exploited as two different hydration levels of collagen matrices. Genipin solution was used to induce crosslinking in collagen matrices. Biaxial stress relaxation tests were performed to characterize the viscoelastic behavior of collagen matrices. The rate of stress relaxation of both hydrated and dehydrated collagen matrices shows a linear initial stress level dependency. Increased crosslinking reduces viscosity in collagen gel, but the effect is negligible for thin film. Relaxation time distribution spectrum was obtained from the stress relaxation data by inverse Laplace transform. For most of the collagen matrices, three peaks at the short (0.3s ~1 s), medium (3s ~90 s), and long relaxation time (> 200 s) were observed in the continuous spectrum, which likely corresponds to relaxation mechanisms involve fiber, inter-fibril, and fibril sliding. Splitting of the middle peak was observed at higher initial stress levels suggesting increased structural heterogeneity at the fibril level with mechanical loading. The intensity of the long-term peaks increases with higher initial stress levels indicating the engagement of collagen fibrils at higher levels of tissue strain.

Burns, chronic wounds, osteoarthritis, and uveitis are examples of conditions characterized by local, intense inflammatory responses that can impede healing or even further tissue degradation. The most powerful anti-inflammatory drugs available are often administered systemically, but these carry significant side effects and are not compatible for patients that have underlying complications associated with their condition. Conjugation of monoclonal antibodies that neutralize pro-inflammatory cytokines to high molecular weight hydrophilic polymers has been shown to be an effective strategy for local control of inflammation. Lead formulations are based on antibody inhibitors of tumor necrosis factor-α conjugated to hyaluronic acid having molecular weight greater than 1 MDa. This review will discuss fundamental aspects of medical conditions that could be treated with these conjugates and design principles for preparing these cytokine-neutralizing polymer conjugates. Results demonstrating that infliximab, an approved inhibitor of tumor necrosis factor-α, can be incorporated into the conjugates using a broad range of water-soluble polymers are also presented, along with a prospectus for clinical translation.

Nanotechnology based Pharma has emerged significantly and has influenced the Pharma industry up to a considerable extent. Nanoparticles technology holds a good share of the nanotech Pharma and is significant in comparison with the other domains. Electrospraying technology answers the potential needs of nanoparticle production such as scalability, reproducibility, effective encapsulation etc. Many drugs have been electrosprayed with and without polymer carriers. Drug release characteristics are improved with the incorporation of biodegradable polymer carriers which sustain the release of encapsulated drug. Electrospraying is acknowledged as an important technique for the preparation of nanoparticles with respect to pharmaceutical applications. Herein we attempted to consolidate the reports pertaining to electrospraying and their corresponding therapeutic application area.

Biomaterials are being used for the healthcare applications from ancient times. But subsequent evolution has made them more versatile and has increased their utility. Biomaterials have revolutionized the areas like bioengineering and tissue engineering for the development of novel strategies to combat life threatening diseases. Together with biomaterials, stem cell technology is also being used to improve the existing healthcare facilities. These concepts and technologies are being used for the treatment of different diseases like cardiac failure, fractures, deep skin injuries, etc. Introduction of nanomaterials on the other hand is becoming a big hope for a better and an affordable healthcare. Technological advancements are underway for the development of continuous monitoring and regulating glucose levels by the implantation of sensor chips. Lab-on-a-chip technology is expected to modernize the diagnostics and make it more easy and regulated. Other area which can improve the tomorrow's healthcare is drug delivery. Micro-needles have the potential to overcome the limitations of conventional needles and are being studied for the delivery of drugs at different location in human body. There is a huge advancement in the area of scaffold fabrication which has improved the potentiality of tissue engineering. Most emerging scaffolds for tissue engineering are hydrogels and cryogels. Dynamic hydrogels have huge application in tissue engineering and drug delivery. Furthermore, cryogels being supermacroporous allow the attachment and proliferation of most of the mammalian cell types and have shown application in tissue engineering and bioseparation. With further developments we expect these technologies to hit the market in near future which can immensely improve the healthcare facilities.

AAA is a complex disease that leads to a localized dilation of the infrarenal aorta that develops over years. Longitudinal information in humans has been difficult to obtain for this disease, therefore mouse models have become increasingly used to study the development of AAAs. The objective of this study was to determine any changes that occur in the biomechanical response and fiber microstructure in the ApoE(-/-) AngII mouse model of aneurysm during disease progression. Adult ApoE(-/-) AngII infused mice along with wild-type controls were taken at 14 and 28 d. Aortas were excised and tested simultaneously for biaxial mechanical response and ECM organization. Data sets were fit to a Fung-type constitutive model to give peak strains and stiffness values. Images from two photon microscopy were quantified in order to assess the preferred fiber alignment and degree of fiber orientation. Biomechanical results found significant differences that were present at 14 d had returned to normal by 28 d along with significant changes in fiber orientation and dispersion indicating remodeling occurring within the aneurysmal wall. This return of some of the normal biomechanical function, in addition the continuing changes that occur in the microstructure suggest a restorative response that occurs in the ApoE(-/-) AngII infused model after the initial aneurysm formation.

Organogenesis, such as long tubule self-organization, requires long-range coordination of cell mechanics to arrange cell positions and to remodel the extracellular matrix. While the current mainstream in the field of tissue morphogenesis focuses primarily on genetics and chemical signaling, the influence of cell mechanics on the programming of patterning cues in tissue morphogenesis has not been adequately addressed. Here, we review experimental evidence and propose quantitative mechanical models by which cells can create tubular patterns.

Zinc oxide (ZnO) is a widely used commercial material that is finding use in wound healing applications due to its antimicrobial properties. Our study demonstrates a novel approach for coating ZnO with precise thickness control onto 20 nm and 100 nm pore diameter anodized aluminum oxide using atomic layer deposition (ALD). ZnO was deposited throughout the nanoporous structure of the anodized aluminum oxide membranes. An 8 nm-thick coating of ZnO, previously noted to have antimicrobial properties, was cytotoxic to cultured macrophages. After 48 h, ZnO-coated 20 nm and 100 nm pore anodized aluminum oxide significantly decreased cell viability by ≈65% and 54%, respectively, compared with cells grown on uncoated anodized aluminum oxide membranes and cells grown on tissue culture plates. Pore diameter (20-200 nm) did not influence cell viability.

Combining technologies to engineer scaffolds that can offer physical and chemical cues to cells is an attractive approach in tissue engineering and regenerative medicine. In this study, we have fabricated polymer-ceramic hybrid scaffolds for bone regeneration by combining rapid prototyping (RP), electrospinning (ESP) and a biomimetic coating method in order to provide mechanical support and a physico-chemical environment mimicking both the organic and inorganic phases of bone extracellular matrix (ECM). Poly(ethylene oxide terephthalate)-poly(buthylene terephthalate) (PEOT/PBT) block copolymer was used to produce three dimensional scaffolds by combining 3D fiber (3DF) deposition, and ESP, and these constructs were then coated with a Ca-P layer in a simulated physiological solution. Scaffold morphology and composition were studied using scanning electron microscopy (SEM) coupled to energy dispersive X-ray analyzer (EDX) and Fourier Tranform Infrared Spectroscopy (FTIR). Bone marrow derived human mesenchymal stromal cells (hMSCs) were cultured on coated and uncoated 3DF and 3DF + ESP scaffolds for up to 21 d in basic and mineralization medium and cell attachment, proliferation, and expression of genes related to osteogenesis were assessed. Cells attached, proliferated and secreted ECM on all the scaffolds. There were no significant differences in metabolic activity among the different groups on days 7 and 21. Coated 3DF scaffolds showed a significantly higher DNA amount in basic medium at 21 d compared with the coated 3DF + ESP scaffolds, whereas in mineralization medium, the presence of coating in 3DF+ESP scaffolds led to a significant decrease in the amount of DNA. An effect of combining different scaffolding technologies and material types on expression of a number of osteogenic markers (cbfa1, BMP-2, OP, OC and ON) was observed, suggesting the potential use of this approach in bone tissue engineering.