Polydimethylsiloxane (PDMS) is the predominant material used for organ-on-a-chip devices and microphysiological systems (MPSs) due to its ease-of-use, elasticity, optical transparency, and inexpensive microfabrication. However, the absorption of small hydrophobic molecules by PDMS and the limited capacity for high-throughput manufacturing of PDMS-laden devices severely limit the application of these systems in personalized medicine, drug discovery, in vitro pharmacokinetic/pharmacodynamic (PK/PD) modeling, and the investigation of cellular responses to drugs. Consequently, the relatively young field of organ-on-a-chip devices and MPSs is gradually beginning to make the transition to alternative, nonabsorptive materials for these crucial applications. This review examines some of the first steps that have been made in the development of organ-on-a-chip devices and MPSs composed of such alternative materials, including elastomers, hydrogels, thermoplastic polymers, and inorganic materials. It also provides an outlook on where PDMS-alternative devices are trending and the obstacles that must be overcome in the development of versatile devices based on alternative materials to PDMS.

There is a lack of formal scientific evidence on how best to manage women with a family history of breast cancer, in terms both of communicating about their risk of developing the disease and of advising about the optimal risk management strategy. It is vital that services offered to these women are adequately evaluated to inform future practice. This paper reports data from an ongoing longitudinal study of the knowledge, attitudes and behavioural and emotional responses of women attending a familial breast cancer clinic in SE Scotland. The clinic was established in 1992, and at that time there were no published psychological data available from the small number of similar clinics in the UK. We were aware of the subsequently published assessments from Manchester of womenÕs perceptions of their risk of developing breast cancer (Evans et al, 1993(Evans et al, , 1994. The same method of assessing risk perceptions was therefore adopted in this study. In spite of a subsequent proliferation of cancer risk counselling clinics there has remained a dearth of published reports evaluating the services offered.The concerns when our clinic opened were that the women seeking referral would be characterized by high anxiety and not necessarily at significantly increased risk. A further concern was that the process of counselling about cancer risk would be anxiety provoking, particularly for those who would be told that their risk was greater than they had previously thought. In the current state of knowledge, the information that can be given about individual risk and the efficacy of available risk management strategies is highly probabilistic. It was recognized that this uncertainty could also generate anxiety. Key issues were therefore to assess womenÕs perceptions of their risk of developing breast cancer and the psychological morbidity associated with cancer risk counselling.This study was conducted against a background of data accruing from the US to show a substantial proportion of women with a family history of breast cancer with significant levels of psychological distress (Kash et al, 1992) and gross overestimates of their own cancer risk (Lerman et al, 1994a;Gagnon et al, 1996) even after risk counselling (Lerman et al, 1995). High levels of perceived susceptibility and associated anxiety have been shown to interfere with adherence to recommended surveillance programmes (Kash et al, 1992;Lerman et al, 1993). The concern has also been expressed that some women will deal with their concerns by making ill-considered requests for genetic testing or prophylactic surgery (Lerman et al, 1994b). In the UK, Lloyd et al (1996) compared 62 genetic counsellees (with a family history of breast cancer) with a matched group of attenders at a general practitionerÕs (GP) surgery. They found these two groups of women to be similar in terms of the outcome measures used and concluded that the risk of breast cancer was not predictive of psychological morbidity. In this study, risk perceptions were recorded before counselling, but 58% of t...

Injectable, in situ-gelling magnetic composite materials have been fabricated by using aldehyde-functionalized dextran to cross-link superparamagnetic nanoparticles surface-functionalized with hydrazide-functionalized poly(N-isopropylacrylamide) (pNIPAM). The resulting composites exhibit high water contents (82-88 wt.%) while also displaying significantly higher elasticities (G' >60 kPa) than other injectable hydrogels previously reported. The composites hydrolytically degrade via slow hydrolysis of the hydrazone cross-link at physiological temperature and pH into degradation products that show no significant cytotoxicity. Subcutaneous injections indicate only minor chronic inflammation associated with material degradation, with no fibrous capsule formation evident. Drug release experiments indicate the potential of these materials to facilitate pulsatile, "on-demand" changes in drug release upon the application of an external oscillating magnetic field. The injectable but high-strength and externally triggerable nature of these materials, coupled with their biological degradability and inertness, suggest potential biological applications in tissue engineering and drug delivery.

Injectable, covalently in situ forming hydrogels based on poly(N-isopropylacrylamide) have been designed on the basis of mixing hydrazide-functionalized nucleophilic precursor polymers with electrophilic precursor polymers functionalized with a combination of ketone (slow reacting) and aldehyde (fast reacting) functional groups. By tuning the ratio of aldehyde:ketone functional groups as well as the total number of ketone groups in the electrophilic precursor polymer, largely independent control over hydrogel properties including gelation time (from seconds to hours), degradation kinetics (from hours to months), optical transmission (from 1 to 85%), and mechanics (over nearly 1 order of magnitude) can be achieved. In addition, ketone-functionalized precursor polymers exhibit improved cytocompatibility at even extremely high concentrations relative to polymers functionalized with aldehyde groups, even at 4-fold higher functional group densities. Overall, increasing the ketone content of the precursor copolymers can result in in situ-gellable hydrogels with improved transparency and biocompatibility and equivalent mechanics and stimuli-responsiveness while only modestly sacrificing the speed of gel formation.

Nanocomposite in situ-gelling hydrogels containing both superparamagnetic iron oxide nanoparticles (SPIONs) and thermoresponsive microgels are demonstrated to facilitate pulsatile, high-low release of a model drug (4 kDa fluoresceinlabeled dextran). The materials can be injected through a minimally invasive route, facilitate a ∼4-fold enhancement of release when pulsed on relative to the off state, and, in contrast to previous gel-based systems, can maintain pulsatile release properties over multiple cycles and multiple days instead of only hours. Optimal pulsatile release is achieved when the microgel transition temperature is engineered to lie just above the (physiological) incubation temperature. Coupled with the demonstrated degradability of the nanocomposites and the cytocompatibility of all nanocomposite components, we anticipate these nanocomposites have potential to facilitate physiologically relevant, controlled pulsatile drug delivery.