We highlight recent developments in hydrogel materials with biological responsiveness built in. These 'smart' biomaterials change properties in response to selective biological recognition events. When exposed to a biological target (nutrient, growth factor, receptor, antibody, enzyme, or whole cell), molecular recognition events trigger changes in molecular interactions that translate into macroscopic responses, such as swelling/collapse or solution-to-gel transitions. The hydrogel transitions may be used directly as optical readouts for biosensing, linked to the release of actives for drug delivery, or instigate biochemical signaling events that control or direct cellular behavior. Accordingly, bioresponsive hydrogels have gained significant interest for application in diagnostics, drug delivery, and tissue regeneration/wound healing

Enzyme responsive materials (ERMs) are a class of stimuli responsive materials with broad application potential in biological settings. This review highlights current and potential future design strategies for ERMs and provides an overview of the present state of the art in the area. Mischa ZelzerMischa Zelzer completed his first degree in Chemistry at the Technical University Graz (AT) in 2005. He then moved to the UK where he obtained his PhD from the University of Nottingham in 2009. Subsequently, he joined the University of Strathclyde (UK) in 2010 as a postdoctoral researcher. In 2012, Mischa was awarded a Marie Curie Fellowship and moved to the Technical University of Eindhoven (NL). Mischa's research interests are in stimuli responsive materials and interfaces with a particular emphasis on enzyme responsiveness and biological applications. Simon J. ToddSimon J. Todd after obtaining a BSc (Hons) degree in Biomedical Materials Science from the University of Nottingham, including a final year project under Prof. D. Grant on the functionalisation of diamond-like carbon with albumin, took a year out to travel in North America. He completed a PhD in the construction of enzyme responsive surfaces at the University of Manchester supervised by Dr Ulijn and Dr J. Gough. Simon then went on to work for the award-winning start up company Renephra.

We report on the design, stepwise synthesis, and surface analysis of enzyme-responsive surfaces that present cell adhesive RGD sequences on-demand, that is, by enzymatic hydrolysis of inactive RGD containing precursors that carry cleavable steric blocking groups. These surfaces, incorporating poly(ethylene glycol) (PEG) monolayers coupled via epoxy silanes to glass, are functionalized via stepwise solid phase synthesis, presenting a versatile and straightforward approach to preparation of peptide surfaces. Successive amino acid coupling and deprotection steps using fluorenylmethoxycarbonyl (Fmoc) chemistry are verified using surface analysis with time-of-flight secondary-ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). Exposure of surfaces to elastase results in activation of cell binding ligands as demonstrated using osteoblast cells. These surfaces may have applications in spatiotemporally controlled attachment of cells as relevant for three-dimensional tissue engineering scaffolds and cell-based biosensors.

We describe enzyme-triggered activation of cell adhesion ligands tethered to a hydrogel surface to direct the attachment of osteoblast cells on demand

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