Polymeric materials are clinically required for medical devices, as well as controlled drug delivery systems. Depending on the application, the polymer has to provide suitable functionalities, for example, mechanical functions or the capability to actively move, so that an implant can be inserted in a compact shape through key-hole incisions and unfold to its functional shape in the body. Shape-memory polymers, as described herein regarding their general principle, compositions and architectures, have developed to a technology platform that allows the tailored design of such multifunctionality. In this way, defined movements of implants triggered either directly or indirectly, tailored mechanical properties, capability for sterilization, biodegradability, biocompatibility and controlled drug release can be realized. This comprehensive review of the scientific and patent literature illustrates that this technology enables the development of novel medical devices that will be clinically evaluated in the near future.

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The formation of functional tissue is strongly dependent on biochemical as well as physical signals. A common approach in tissue engineering is the application of passive scaffold systems with fixed morphology and stiffness. In this paper, we explored whether mechanically active scaffolds, exhibiting self-sufficient shape changes under physiological conditions, can be prepared from radio-opaque shape-memory polymer composites (SMPCs). The influence of different thermomechanical treatments on the kinetics of the shape change was studied. Radio-opaque SMPCs were obtained by incorporation of barium sulfate (BaSO 4 ) microparticles (up to 40 wt%) into an amorphous polyether urethane (PEU) via co-extrusion technique. The shape-memory properties of the composites were investigated by cyclic, thermomechanical tensile tests consisting of a specific shape-memory creation procedure (SMCP), in which the programming temperature (T prog ) was varied, followed by recovery under stress-free condition, enabling the determination of the switching temperature (T sw ). An almost complete recovery with shape recovery rate (R r ) values ranging from 88% to 98% was realized within a small temperature interval of DT rec % 30-C for all composites, while T sw was found to be close to the applied T prog . The feasibility of actively moving scaffolds was demonstrated using model scaffolds, where originally square-shaped pores were temporarily fixed in an expanded circular shape at different T prog . We found that the kinetics of the shape change obtained under physiological conditions could be adjusted by variation of T prog between 1 and 6 hr. Such radio-opaque scaffolds could serve as model scaffolds for investigating the active mechanical stimulation of cells in vitro or in vivo.

The cyclic (c)AMP responsive element binding protein (CREB) plays a key role in many cellular processes, including differentiation, proliferation, and signal transduction. Furthermore, CREB overexpression was found in tumors of distinct origin and evidence suggests an association with tumorigenicity. To establish a mechanistic link between HER-2/neu-mediated transformation and CREB protein expression and function, in vitro models of HER-2/neu-overexpressing and HER-2/neu-negative/silenced counterparts as well as human mammary carcinoma lesions with defined HER-2/neu status were used. HER-2/neu overexpression resulted in the induction and activation of CREB protein in vitro and in vivo, whereas short hairpin RNA (shRNA)-mediated inhibition of HER-2/neu correlated with downregulated CREB activity. CREB activation in HER-2/neu-transformed cells enhanced distinct signal transduction pathways, whereas their inhibition negatively interfered with CREB expression and/or activation. CREB downregulation in HER-2/neu-transformed cells by shRNA and by the inhibitors KG-501 and lapatinib caused morphologic changes, reduced cell proliferation with G 0 -G 1 cell-cycle arrest, which was rescued by CREB expression. This was accompanied by reduced cell migration, wound healing, an increased fibronectin adherence, invasion, and matrix metalloproteinase expression. In vivo shCREB-HER-2/neu þ cells, but not control cells, exerted a significantly decreased tumorgenicity that was associated with decreased proliferative capacity, enhanced apoptosis, and increased frequency of T lymphocytes in peripheral blood mononuclear cells. Thus, CREB plays an important role in the HER-2/neu-mediated transformation by altering in vitro and in vivo growth characteristics.

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Mechanical conditioning can serve as a potent tool to influence mechano-responsive cells, which plays a prominent role during formation and regeneration of functional tissue. Recently, the differentiation of mesenchymal stem cells could be influenced by the local stiffness of hydrogels used as 2D substrates. However, the mechanical properties and the swellability of hydrogels in physiological liquids are difficult to control precisely as their properties strongly depend on physical parameters like ionic strength or pH value. Here, we explored amorphous, hydrophobic poly(n-butyl acrylate) networks (cPnBA) as soft substrates for cell culture system with adjustable mechanical properties. cPnBAs were synthesized via bulk radical polymerization from n-butyl acrylate (nBA) and poly(propylene glycol) dimethacrylate (PPGDMA) as crosslinker. The Young's modulus for cPnBAs determined by tensile tests could be systematically adjusted from 100 kPa to 10 MPa by increasing the PPGDMA-content at ambient temperature, while the glass transition temperature (T g ) was found to increase from S46 to S22-C. All cPnBAs exhibited similar surface properties with a surface roughness (R q ) in the range from 1.4 to 0.4 mm and advancing contact angles from 115-to 100-, which remained constant after ethylene oxide sterilization. The extracts of sterilized materials were tested for cytotoxic effects with L929 cells. All tested samples were non-cytotoxic. The functional integrity of cell membranes and mitochondrial activity stayed unaffected. The investigated polymer networks are promising candidates as soft substrates for passive mechanical stimulation of cells in vitro in cell culture devices or in vivo as implant coatings.