Heart Valve Tissue Engineering: Concepts, Approaches, Progress, and Challenges

Potential applications of tissue engineering in regenerative medicine range from structural tissues to organs with complex function. This review focuses on the engineering of heart valve tissue, a goal which involves a unique combination of biological, engineering, and technological hurdles. We emphasize basic concepts, approaches and methods, progress made, and remaining challenges. To provide a framework for understanding the enabling scientific principles, we first examine the elements and features of normal heart valve functional structure, biomechanics, development, maturation, remodeling, and response to injury. Following a discussion of the fundamental principles of tissue engineering applicable to heart valves, we examine three approaches to achieving the goal of an engineered tissue heart valve: (1) cell seeding of biodegradable synthetic scaffolds, (2) cell seeding of processed tissue scaffolds, and (3) in-vivo repopulation by circulating endogenous cells of implanted substrates without prior in-vitro cell seeding. Lastly, we analyze challenges to the field and suggest future directions for both preclinical and translational (clinical) studies that will be needed to address key regulatory issues for safety and efficacy of the application of tissue engineering and regenerative approaches to heart valves. Although modest progress has been made toward the goal of a clinically useful tissue engineered heart valve, further success and ultimate human benefit will be dependent upon advances in biodegradable polymers and other scaffolds, cellular manipulation, strategies for rebuilding the extracellular matrix, and techniques to characterize and potentially non-invasively assess the speed and quality of tissue healing and remodeling

Polymeric triple-shape materials

Shape-memory polymers represent a promising class of materials that can move from one shape to another in response to a stimulus such as heat. Thus far, these systems are dual-shape materials. Here, we report a triple-shape polymer able to change from a first shape (A) to a second shape (B) and from there to a third shape (C). Shapes B and C are recalled by subsequent temperature increases. Whereas shapes A and B are fixed by physical cross-links, shape C is defined by covalent cross-links established during network formation. The triple-shape effect is a general concept that requires the application of a two-step programming process to suitable polymers and can be realized for various polymer networks whose molecular structure allows formation of at least two separated domains providing pronounced physical cross-links. These domains can act as the switches, which are used in the two-step programming process for temporarily fixing shapes A and B. It is demonstrated that different combinations of shapes A and B for a polymer network in a given shape C can be obtained by adjusting specific parameters of the programming process. Dual-shape materials have already found various applications. However, as later discussed and illustrated by two examples, the ability to induce two shape changes that are not limited to be unidirectional rather than one could potentially offer unique opportunities, such as in medical devices or fasteners

Expandable Temperature-Responsive Polymeric Nanotubes

Materials with the ability of dimensional changes on demand exhibit many potential applications ranging from adaptive composites that mimic biological functions under extreme conditions to microfluidics or neural implants to stimulate components of the nervous systems. These studies show the synthesis of temperature-induced reversibly expandable nanotubes that were prepared by polymerization of N-isopropylacrylamide (NIPAAM) in the presence of biologically active 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) diacetylenic phospholipids (PL). As a result, thermally responsive poly-NIPAM-phospholipid nanotubes (PNNTs) were prepared. Polymerization reactions occur within hydrophilic regions of PL bilayers, whereas PL hydrophobic zones facilitate transport and supply of the monomer for polymerization. The unique feature of PNNTs is that, above 37 °C, the outer diameter (OD) as well as the wall thickness (WT) shrink by 20 and 55%, respectively, whereas the inner diameter (ID) increases by 16%. This behavior is attributed to the PNIPAM backbone buckling induced by local rearrangements within PL bilayered morphologies. The presence of acetylenic moieties along the PL bilayers in PNNTs provides an opportunity for irreversible “locking” of designable dimensions, which is facilitated by the formation of cross-linked PNNTs (CL-PNNTs)

Smart nanofibers with a photoresponsive surface for controlled release

10.1021/am900526uACS Applied Materials and Interfaces1112424-242