Stimuli-responsive polymeric materials is one of the fastest growing fields of the 21st century, with the annual number of papers published more than quadrupling in the last ten years. The responsiveness of polymer solution assemblies and surfaces to biological stimuli (e.g. pH, reduction-oxidation, enzymes, glucose) and externally applied triggers (e.g. temperature, light, solvent quality) shows particular promise for various biomedical applications including drug delivery, tissue engineering, medical diagnostics, and bioseparations. Furthermore, the integration of copolymer architectures into stimuli-responsive materials design enables exquisite control over the locations of responsive sites within self-assembled nanostructures. The combination of new synthesis techniques and well-defined copolymer self-assembly has facilitated substantial developments in stimuli-responsive materials in recent years. In this tutorial review, we discuss several methods that have been employed to synthesize self-assembling and stimuli-responsive copolymers for biomedical applications, and we identify common themes in the response mechanisms among the targeted stimuli. Additionally, we highlight parallels between the chemistries used for generating solution assemblies and those employed for creating copolymer surfaces.

This work examines the release of a model water-soluble compound from electrospun polymer nanofiber assemblies. Such release attracts attention in relation to biomedical applications, such as controlled drug delivery. It is also important for stem cell attachment and differentiation on biocompatible electrospun nanofiber scaffolds containing growth factors, which have been encapsulated by means of electrospinning. Typically, the release mechanism has been attributed to solid-state diffusion of the encapsulated compound from the fibers into the surrounding aqueous bath. Under this assumption, a 100% release of the encapsulated compound is expected in a certain (long) time. The present work focuses on certain cases where complete release does not happen, which suggests that solid-state diffusion may not be the primary mechanism at play. We show that in such cases the release rate can be explained by desorption of the embedded compound from nanopores in the fibers or from the outer surface of the fibers in contact with the water bath. After release, the water-soluble compound rapidly diffuses in water, whereas the release rate is determined by the limiting desorption stage. A model system of Rhodamine 610 chloride fluorescent dye embedded in electrospun monolithic poly(methylmethacrylate) (PMMA) or poly(caprolactone) (PCL) nanofibers, in nanofibers electrospun from PMMA/PCL blends, or in core-shell PMMA/PCL nanofibers is studied. Both the experimental results and theory point at the above mentioned desorption-related mechanism, and the predicted characteristic time, release rate, and effective diffusion coefficient agree fairly well with the experimental data. A practically important outcome of this surface release mechanism is that only the compound on the fiber and pore surfaces can be released, whereas the material encapsulated in the bulk cannot be freed within the time scales characteristic of the present experiments (days to months). Consequently, in such cases, complete release is impossible. We also demonstrate how the release rate can be manipulated by the polymer content and molecular weight affecting nanoporosity and the desorption enthalpy, as well as by the nanofiber structure (monolithic fibers, fibers from polymer blends, and core-shell fibers). In particular, it is shown that, by manipulating the above parameters, release times from tens of hours to months can be attained.

The elastic and viscous properties of self-assembled amphiphilic membranes dictate the intricate hierarchy of their structure and dynamics ranging from the diffusion of individual molecules to the large-scale deformation of the membrane. We previously demonstrated that neutron spin echo spectroscopy measurements of model amphiphilic membranes can access the naturally occurring submicrosecond membrane motions, such as bending and thickness fluctuations. Here we show how the experimentally measured fluctuation parameters can be used to determine the inherent membrane properties and demonstrate how membrane viscosity and compressibility modulus are influenced by lipid composition in a series of simple phosphatidylcholine bilayers with different tail lengths as a function of temperature. This approach highlights the interdependence of the bilayer elastic and viscous properties and the collective membrane dynamics and opens new avenues to investigating the mechanical properties of more complex and biologically inspired systems.

The solution self-assembly of macromolecular amphiphiles offers an efficient, bottom-up strategy for producing well--defined nanocarriers, with applications ranging from drug delivery to nanoreactors. Typically, the generation of uniform nanocarrier architecturesis controlled by processing methods that rely upon cosolvent mixtures. These preparation strategies hinge on the assumption that macromolecular solution nanostructures are kinetically stable following transfer from an organic/aqueous cosolvent into aqueous solution. Herein we demonstrate that unequivocal step-change shifts in micelle populations occur over several weeks following transfer into a highly selective solvent. The unexpected micelle growth evolves through a distinct bimodal distribution separated by multiple fusion events and critically depends on solution agitation. Notably, these results underscore fundamental similarities between assembly processes in amphiphilic polymer, small molecule, and protein systems. Moreover, the non-equilibrium micelle size increase can have a major impact on the assumed stability of solution assemblies, for which performance is dictated by nanocarrier size and structure.