Kibret Mequanint

Small-diameter vascular tissue engineering

Vascular occlusion remains the leading cause of death in Western countries, despite advances made in balloon angioplasty and conventional surgical intervention. Vascular surgery, such as CABG surgery, arteriovenous shunts, and the treatment of congenital anomalies of the coronary artery and pulmonary tracts, requires biologically responsive vascular substitutes. Autografts, particularly saphenous vein and internal mammary artery, are the gold-standard grafts used to treat vascular occlusions. Prosthetic grafts have been developed as alternatives to autografts, but their low patency owing to short-term and intermediate-term thrombosis still limits their clinical application. Advances in vascular tissue engineering technology—such as self-assembling cell sheets, as well as scaffold-guided and decellularized-matrix approaches—promise to produce responsive, living conduits with properties similar to those of native tissue. Over the past decade, vascular tissue engineering has become one of the fastest-growing areas of research, and is now showing some success in the clinic.

Synthesis and Electrospinning of ε-Polycaprolactone-Bioactive Glass Hybrid Biomaterials via a Sol−Gel Process

Strategies of bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix (ECM) as templates onto which cells attach, multiply, migrate, and function. For this purpose, hybrid biomaterials based on smart combinations of biodegradable polymers and bioactive glasses (BGs) are of particular interest, since they exhibit tailored physical, biological, and mechanical properties, as well as predictable degradation behavior. In this study, hybrid biomaterials with different organic-inorganic ratios were successfully synthesized via a sol-gel process. Poly(ε-caprolactone) (PCL) and tertiary bioactive glass (BG) with a glass composition of 70 mol % SiO(2), 26 mol % CaO, and 4 mol % of P(2)O(5) were used as the polymer and inorganic phases, respectively. The polymer chains were successfully introduced into the inorganic sol while the networks were formed. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analyses (TGA), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) were used to investigate the presence of different chemical groups, structural crystallinity, thermal property, elemental composition, and homogeneity of the synthesized hybrid biomaterials. Identification of chemical groups and the presence of molecular interaction by hydrogen bonding between the organic and inorganic phases was confirmed by FTIR. The XRD patterns showed that all PCL/BG hybrids (up to 60% polymer content) were amorphous. The TGA study revealed that the PCL/BG hybrid biomaterials were thermally stable, and good agreement was observed between the experimental and theoretical organic-inorganic ratios. The SEM/EDX results also revealed a homogeneous elemental distribution and demonstrated the successful incorporation of all the elements in the hybrid system. Finally, these synthesized hybrid biomaterials were successfully electrospun into 3D scaffolds. The resultant fibers have potential use as scaffolds for bone regeneration.

Nano-structure phosphorus-containing polyurethane dispersions: synthesis and crosslinking with melamine formaldehyde resin

Abstract Nano-particle-size phosphated polyurethane dispersions were synthesised from phosphorus-containing macroglycol, bis (hydroxymethyl) propionic acid and methylene-bis-(4-isocyanatocyclohexane) (H 12 MDI). After the carboxylic acid groups of the phosphated polyurethane were neutralised by suitable bases, water was added to form the phosphated polyurethane dispersion. Chain flexibility affected particle-size reduction because flexible particles are more deformable in a shear field. During phase inversion the dispersed phase can more easily be broken into smaller particles. Depending on the number of hydrophilic groups present, the dispersion can be obtained in a very finely divided form, so that it practically has the appearance of a solution. Crosslinking of the dispersions with melamine showed that hexamethoxymethyl melamine does not self-condense during the curing and co-condensation was predominant. It was further shown that the cure response of the polyurethane dispersions was affected by the nature of the neutralising amine. Triethanolamine neutralised dispersions gave very poor cure response compared with triethylamine due to the low-volatility and the tendency to enter side reaction with the melamine.

Bioactive and biodegradable nanocomposites and hybrid biomaterials for bone regeneration.

Strategies for bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix and act as templates onto which cells attach, multiply, migrate and function. Of particular interest are nanocomposites and organic-inorganic (O/I) hybrid biomaterials based on selective combinations of biodegradable polymers and bioactive inorganic materials. In this paper, we review the current state of bioactive and biodegradable nanocomposite and O/I hybrid biomaterials and their applications in bone regeneration. We focus specifically on nanocomposites based on nano-sized hydroxyapatite (HA) and bioactive glass (BG) fillers in combination with biodegradable polyesters and their hybrid counterparts. Topics include 3D scaffold design, materials that are widely used in bone regeneration, and recent trends in next generation biomaterials. We conclude with a perspective on the future application of nanocomposites and O/I hybrid biomaterials for regeneration of bone.

Prosthetic aortic heart valves: Modeling and design

Although heart valve replacement is among the most common cardiovascular surgical procedures, their outcome is often difficult to predict. One of the reasons is the design and choice of the materials used for the fabrication of the prostheses. This review paper describes the use of modeling techniques in prosthetic heart valve (HV) design and aims at the justification and development of a polymer based trileaflet mechanical heart valve (MHV). The closing/opening phase behavior of the bileaflet MHV was investigated. The potential problem of valve failure due to crack propagation in the brittle pyrolytic carbon leaflet was also discussed. These studies suggest that although bileaflet MHV performs satisfactorily, there are justifications for improvement. Since the native aortic HV is trileaflet and made of anisotropic and hyperelastic tissue, one possible approach to a better MHV design is based on our ability to closely mimic the natural geometry and biomaterial properties.

Modification, crosslinking and reactive electrospinning of a thermoplastic medical polyurethane for vascular graft applications.

Thermoplastic polyurethanes are used in a variety of medical devices and experimental tissue engineering scaffolds. Despite advances in polymer composition to improve their stability, the correct balance between chemical and mechanical properties is not always achieved. A model compound (MC) simulating the structure of a widely used medical polyurethane (Pellethane) was synthesized and reacted with aliphatic and olefinic acyl chlorides to study the reaction site and conditions. After adopting the conditions to the olefinic modification of Pellethane, processing into flat sheets, and crosslinking by thermal initiation or ultraviolet radiation, mechanical properties were determined. The modified polyurethane was additionally electrospun under ultraviolet light to produce a crosslinked tubular vascular graft prototype. Model compound studies showed reaction at the carbamide nitrogen, and the modification of Pellethane with pentenoyl chloride could be accurately controlled to up to 20% (correlation: rho=0.99). Successful crosslinking was confirmed by insolubility of the materials. Initiator concentrations were optimized and the crosslink densities shown to increase with increasing modification. Crosslinking of Pellethane containing an increasing number of pentenoyl groups resulted in decreases (up to 42%, p<0.01) in the hysteresis and 44% in creep (p<0.05), and in a significant improvement in degradation resistance in vitro. Modified Pellethane was successfully electrospun into tubular grafts and crosslinked using UV irradiation during and after spinning to render them insoluble. Prototype grafts had sufficient burst pressure (>550 mm Hg), and compliances of 12.1+/-0.8 and 6.2+/-0.3%/100 mm Hg for uncrosslinked and crosslinked samples, respectively. It is concluded that the viscoelastic properties of a standard thermoplastic polyurethane can be improved by modification and subsequent crosslinking, and that the modified material may be electrospun and initiated to yield crosslinked scaffolds. Such materials hold promise for the production of vascular and other porous scaffolds, where decreased hysteresis and creep may be required to prevent aneurismal dilation.

Thermogravimetric study of phosphated polyurethane ionomers

Segmented polyurethane dispersions containing bound phosphate groups on the soft segment have been synthesised from a phosphate containing macroglycol, a diisocyanate and a chain extender. TGA study of these polymers has revealed three stages of degradation. The initial weight loss temperature for the phosphated polyurethane dispersions was lower than the ones without phosphate indicating that degradation started at the soft segment that contains the phosphate groups. The degradation profile of the dispersions was also dependent on the neutralising base. The higher char yield of phosphated polyurethanes was related to its fire retardant property and could be used as fire retardant coatings.

Versatile Biodegradable Poly(ester amide)s Derived from α-Amino Acids for Vascular Tissue Engineering

Biodegradable poly(ester amide) (PEA) biomaterials derived from α-amino acids, diols, and diacids are promising materials for biomedical applications such as tissue engineering and drug delivery because of their optimized properties and susceptibility for either hydrolytic or enzymatic degradation. The objective of this work was to synthesize and characterize biodegradable PEAs based on the α-amino acids l-phenylalanine and l-methionine. Four different PEAs were prepared using 1,4-butanediol, 1,6-hexanediol, and sebacic acid by interfacial polymerization. High molecular weight PEAs with narrow polydispersity indices and excellent film-forming properties were obtained. The incubation of these PEAs in PBS and chymotrypsin indicated that the polymers are biodegradable. Human coronary artery smooth muscle cells were cultured on PEA films for 48 h and the results showed a well-spread morphology. Porous 3D scaffolds fabricated from these PEAs were found to have excellent porosities indicating the utility of these polymers for vascular tissue engineering.

Hydroxyapatite formation on sol-gel derived poly(ε-caprolactone)/bioactive glass hybrid biomaterials.

Investigation of novel biomaterials for bone regeneration is based on the development of scaffolds that exhibit bone-bonding ability, biocompatibility, and sufficient mechanical strength. In this study, using novel poly (ε-caprolactone)/bioactive glass (PCL/BG) hybrids with different organic/inorganic ratios, the effects of BG contents on the in vitro bone-like hydroxyapatite (HA) formation, mechanical properties, and biocompatibility were investigated. Rapid precipitation of HA on the PCL/BG hybrid surfaces were observed after incubating in simulated body fluid (SBF) for only 6 h, as confirmed by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), Fourier-transform infrared spectroscopy (FTIR), and inductively coupled plasma atomic emission spectroscopy (ICPS). The ICPS elemental analysis results were further analyzed in terms of the Ca(2+) and PO4(3-) which were consumed to form the apatite layer. The results revealed that the rate and total amount of HA deposition decreased with an increase in PCL content. The compressive modulus and strength of the PCL/BG hybrids increased with the decrease in PCL content. The highest values were achieved at the lowest PCL content (10 wt %) and were around, 90 MPa and 1.4 GPa, respectively. To evaluate the cytotoxicity of PCL/BG bioactive hybrids, MC3T3-E1 osteoblast-like cells were cultured for up to 72 h. Our data indicated that whereas initial cell attachment was marginally lower than the control tissue culture poly styrene (TCPS) surface, the hybrid materials promoted cell growth in a time-dependent manner. Cell viability within the different PCL/BG hybrid samples appeared to be influenced by compositional differences whereby higher PCL contents correlated with slight reduction in cell viability. Taken together, this study adds important new information to our knowledge on hydroxyapatite formation, mechanical properties, and cytotoxic effects of PCL/BG hybrids prepared by the sol-gel process using a tertiary glass composition and may have considerable potential for bone tissue regeneration applications.

Strategies in functional poly(ester amide) syntheses to study human coronary artery smooth muscle cell interactions.

The design of new generation cardiovascular biomaterials focuses on biomimetic properties that are capable of eliciting specific cellular responses and directing new tissue formation. Synthetic poly(ester amide)s (PEAs) containing α-amino acid residues have the potential to elicit favorable cellular responses. Furthermore, they are biodegradable owing to the incorporation of naturally occurring amino acids. In this study, a family of PEAs was synthesized from selected α-amino acids using both solution and interfacial polymerization approaches to optimize their properties for vascular tissue engineering applications. By careful selection of the monomers and the polymerization approach, high-molecular-weight PEAs with low glass-transition temperatures were obtained. Human coronary artery smooth muscle cells (HCASMCs) cultured directly on bare PEA films attached and spread well up to 7 days of culture. Moreover, cell viability was significantly enhanced on all nonfunctional PEAs compared with tissue culture polystyrene controls. The trifluoroacetic acid salt of the lysine-containing functional PEAs was found to retard cell growth but still supported cell viability up to 5 days of culture. Immunostaining of HCASMCs revealed strong vinculin expression, suggesting that the HCASMCs initiated cellular processes for focal adhesion contacts with all PEA surfaces. Conversely, smooth muscle α-actin expression was not abundant on the PEA surfaces, suggesting a proliferative smooth muscle cell phenotype. Altogether, our results indicate that these PEAs are promising materials for vascular tissue engineering scaffolds.