Guillermo A. Ameer

A tough biodegradable elastomer

Biodegradable polymers have significant potential in biotechnology and bioengineering. However, for some applications, they are limited by their inferior mechanical properties and unsatisfactory compatibility with cells and tissues. A strong, biodegradable, and biocompatible elastomer could be useful for fields such as tissue engineering, drug delivery, and in vivo sensing. We designed, synthesized, and characterized a tough biodegradable elastomer from biocompatible monomers. This elastomer forms a covalently crosslinked, three-dimensional network of random coils with hydroxyl groups attached to its backbone. Both crosslinking and the hydrogen-bonding interactions between the hydroxyl groups likely contribute to the unique properties of the elastomer. In vitro and in vivo studies show that the polymer has good biocompatibility. Polymer implants under animal skin are absorbed completely within 60 days with restoration of the implantation sites to their normal architecture.

Biodegradable polyester elastomers in tissue engineering.

Tissue engineering often makes use of biodegradable scaffolds to guide and promote controlled cellular growth and differentiation in order to generate new tissue. There has been significant research regarding the effects of scaffold surface chemistry and degradation rate on tissue formation and the importance of these parameters is widely recognised. Nevertheless, studies describing the role of mechanical stimuli during tissue development and function suggest that the mechanical properties of the scaffold will also be important. In particular, scaffold mechanics should be taken into account if mechanical stimulation, such as cyclic strain, will be incorporated into strategies to grow improved tissues or the target tissue to be replaced has elastomeric properties. Biodegradable polyesters, such as polyglycolide, polylactide and poly(lactide-co-glycolide), although commonly used in tissue engineering, undergo plastic deformation and failure when exposed to long-term cyclic strain, limiting their use in engineering elastomeric tissues. This review will cover the latest advances in the development of biodegradable polyester elastomers for use as scaffolds to engineer tissues, such as heart valves and blood vessels.

A biodegradable composite scaffold for cell transplantation

Cell transplantation is rapidly becoming a therapeutic option to treat disease and injury. However, standard techniques for cell seeding on non‐woven polymer meshes or within gels may not be suitable for immediate implantation or surgical manipulations of freshly isolated cells. Therefore, a biodegradable composite system was developed as a way to rapidly entrap cells within a support of predefined shape to potentially facilitate cell delivery into a target site (e.g. meniscal tears in the avascular zone). The composite construct consisted of freshly isolated cells, in this case pig chondrocytes, entrapped in a fibrin gel phase and dispersed throughout the void volume of a polyglycolic acid (PGA) non‐woven mesh. Composites were cultured for up to 4 weeks. In vitro degradation of fibrin gel was evaluated via gel‐entrapped urokinase. At 28 days in culture, glycosaminoglycan (GAG) content per cell in the composite scaffolds was 2.6 times that of the PGA‐only cell construct group and 88% that of native pig cartilage. Total collagen content per cell in the composite scaffolds was not significantly different from the PGA‐only cell construct group (P > 0.02) and represented 40% of the value determined for native cartilage. Varying the concentration of entrapped urokinase could effect controlled degradation of fibrin gel.

The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts

Prosthetic vascular grafts do not mimic the antithrombogenic properties of native blood vessels and therefore have higher rates of complications that involve thrombosis and restenosis. We developed an approach for grafting bioactive heparin, a potent anticoagulant glycosaminoglycan, to the lumen of ePTFE vascular grafts to improve their interactions with blood and vascular cells. Heparin was bound to aminated poly(1,8-octanediol-co-citrate) (POC) via its carboxyl functional groups onto POC-modified ePTFE grafts. The bioactivity and stability of the POC-immobilized heparin (POC-Heparin) were characterized via platelet adhesion and clotting assays. The effects of POC-Heparin on the adhesion, viability and phenotype of primary endothelial cells (EC), blood outgrowth endothelial cells (BOECs) obtained from endothelial progenitor cells (EPCs) isolated from human peripheral blood, and smooth muscle cells were also investigated. POC-Heparin grafts maintained bioactivity under physiologically relevant conditions in vitro for at least one month. Specifically, POC-Heparin-coated ePTFE grafts significantly reduced platelet adhesion and inhibited whole blood clotting kinetics. POC-Heparin supported EC and BOEC adhesion, viability, proliferation, NO production, and expression of endothelial cell-specific markers von Willebrand factor (vWF) and vascular endothelial-cadherin (VE-cadherin). Smooth muscle cells cultured on POC-Heparin showed increased expression of α-actin and decreased cell proliferation. This approach can be easily adapted to modify other blood contacting devices such as stents where antithrombogenicity and improved endothelialization are desirable properties.

Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1,8-octanediol-co-citrate) based thin films

Bladder regeneration studies have yielded inconclusive results possibly due to the use of unfavorable cells and primitive scaffold design. We hypothesized that human mesenchymal stem cells seeded onto poly(1,8-octanediol-co-citrate) elastomeric thin films would provide a suitable milieu for partial bladder regeneration. POCfs were created by reacting citric acid with 1,8-octanediol and seeded on opposing faces with human MSCs and urothelial cells; normal bladder smooth muscle cells and UCs, or unseeded POCfs. Partial cystectomized nude rats were augmented with the aforementioned POCfs, enveloped with omentum and sacrificed at 4 and 10 weeks. Isolated bladders were subjected to Trichrome and anti-human gamma-tubulin, calponin, caldesmon, smooth muscle gamma-actin, and elastin stainings. Mechanical testing of POCfs revealed a Youngs modulus of 138 kPa with elongation 137% its initial length without permanent deformation demonstrating its high uniaxial elastic potential. Trichrome and immunofluorescent staining of MSC/UC POCf augmented bladders exhibited typical bladder architecture with muscle bundle formation and the expression and retention of bladder smooth muscle contractile proteins of human derivation. Quantitative morphometry of MSC/UC samples revealed muscle/collagen ratios approximately 1.75x greater than SMC/UC controls at 10 weeks. Data demonstrate MSC seeded POCfs support partial regeneration of bladder tissue in vivo.

Biodegradable elastomers and silicon nanomembranes/nanoribbons for stretchable, transient electronics, and biosensors

Transient electronics represents an emerging class of technology that exploits materials and/or device constructs that are capable of physically disappearing or disintegrating in a controlled manner at programmed rates or times. Inorganic semiconductor nanomaterials such as silicon nanomembranes/nanoribbons provide attractive choices for active elements in transistors, diodes and other essential components of overall systems that dissolve completely by hydrolysis in biofluids or groundwater. We describe here materials, mechanics, and design layouts to achieve this type of technology in stretchable configurations with biodegradable elastomers for substrate/encapsulation layers. Experimental and theoretical results illuminate the mechanical properties under large strain deformation. Circuit characterization of complementary metal-oxide-semiconductor inverters and individual transistors under various levels of applied loads validates the design strategies. Examples of biosensors demonstrate possibilities for stretchable, transient devices in biomedical applications.

Novel Biodegradable Shape‐Memory Elastomers with Drug‐Releasing Capabilities

IO N Citric acid is a commercially important compound with widespread use in the chemical, food and beverage, cleaning, cosmetics, and pharmacological industries. [ 1 ] Recently, it has been used as a basis for the synthesis of biodegradable polyester elastomers. [ 2 , 3 ] Signifi cant research has demonstrated the biocompatibility of polydiolcitrates both in vitro and in vivo, as well as their potential application in tissue engineering (cardiovascular, [ 4 , 5 ] bone, [ 6 ] cartilage, [ 7 ] and bladder [ 8 ] ), bioimaging, [ 9 ]

Recent Insights Into the Biomedical Applications of Shape‐memory Polymers

Shape-memory polymers (SMP) are versatile stimuli-responsive materials that can switch, upon stimulation, from a temporary to a permanent shape. This advanced functionality makes SMP suitable and promising materials for diverse technological applications, including the fabrication of smart biomedical devices. In this paper, advances in the design of SMP are discussed, with emphasis on materials investigated for medical applications. Future directions necessary to bring SMP closer to their clinical application are also highlighted.

Engineering sub-100 nm multi-layer nanoshells

Nanoshells are a novel class of optically tunable nanoparticles that consist of alternating dielectric and metal layers. They can potentially be used as contrast agents for multi-label molecular imaging, provided that the shell thicknesses are tuned to specific ratios. Sub-100 nm multi-layer nanoshells can potentially have improved tissue penetration, generate a strong surface plasmon resonance, and may exhibit absorption peaks in the visible–near-infrared (NIR) spectrum. Herein we describe the synthesis and characterization of bilayered concentric nanoshells with an overall diameter of around 50 nm consisting of a gold core, a tunable silica spacer layer and an outermost gold shell, which is approximately 16 times smaller than previously described multi-layered nanoparticles. The structured nanoshells were visualized by transmission electron microscopy (TEM) at each step of preparation. The absorption spectra of the gold–silica bilayered nanoshells are in good agreement with Mies prediction and their resonance peak position is a function of the relative thickness of silica and gold layers.

The role of nanocomposites in bone regeneration

Tissue engineering utilizes the expertise within the fields of materials science, biology, chemistry, transplantation medicine, and engineering to design materials that can temporarily serve in a structural and/or functional capacity while a defect is regenerated. Of prominence in the realm of regenerative medicine is the issue of bone disease and degeneration, particularly among an increasingly aging population. Traditional methods for bone and joint replacement enjoy increasing success, but restoration of native tissue architecture remains the ideal. Toward this goal, the design of a tissue equivalent that can integrate with native bone must take into account the characteristics of this unique tissue. Firstly, the extracellular matrix of bone is a hierarchical, heterogeneous material that has features with sizes that range from the nanoscale to the macroscale. Secondly, there is synergy between these features that gives rise to a composite material with defined nano-, micro-, and macrophases. Understanding the role of these phases should lead to improved materials to aid bone regeneration. Emulating the structure of bone is difficult; nevertheless, researchers are developing nanocomposite materials that take us one step closer to attaining the mechanical and biological properties of bone. This article discusses the role of nanoscale parameters and interactions in bone and presents a few examples of how engineered nanocomposites attempt to mimic the hierarchical structure of bone in order to achieve tissue regeneration rather than repair.