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Recent experimental and theoretical work clarifying the physical chemistry of blood-protein adsorption from aqueous-buffer solution to various kinds of surfaces is reviewed and interpreted within the context of biomaterial applications, especially toward development of cardiovascular biomaterials. The importance of this subject in biomaterials surface science is emphasized by reducing the “protein-adsorption problem” to three core questions that require quantitative answer. An overview of the protein-adsorption literature identifies some of the sources of inconsistency among many investigators participating in more than five decades of focused research. A tutorial on the fundamental biophysical chemistry of protein adsorption sets the stage for a detailed discussion of the kinetics and thermodynamics of protein adsorption, including adsorption competition between two proteins for the same adsorbent immersed in a binary-protein mixture. Both kinetics and steady-state adsorption can be rationalized using a single interpretive paradigm asserting that protein molecules partition from solution into a three-dimensional (3D) interphase separating bulk solution from the physical-adsorbent surface. Adsorbed protein collects in one-or-more adsorbed layers, depending on protein size, solution concentration, and adsorbent surface energy (water wettability). The adsorption process begins with the hydration of an adsorbent surface brought into contact with an aqueous-protein solution. Surface hydration reactions instantaneously form a thin, pseudo-2D interface between the adsorbent and protein solution. Protein molecules rapidly diffuse into this newly-formed interface, creating a truly 3D interphase that inflates with arriving proteins and fills to capacity within milliseconds at mg/mL bulk-solution concentrations CB. This inflated interphase subsequently undergoes time-dependent (minutes-to-hours) decrease in volume VI by expulsion of either-or-both interphase water and initially-adsorbed protein. Interphase protein concentration CI increases as VI decreases, resulting in slow reduction in interfacial energetics. Steady-state is governed by a net partition coefficient P=true(/CBCItrue). In the process of occupying space within the interphase, adsorbing protein molecules must displace an equivalent volume of interphase water. Interphase water is itself associated with surface-bound water through a network of transient hydrogen bonds. Displacement of interphase water thus requires an amount of energy that depends on the adsorbent surface chemistry/energy. This “adsorption-dehydration” step is the significant free-energy cost of adsorption that controls the maximum amount of protein that can be adsorbed at steady state to a unit adsorbent-surface area (the adsorbent capacity). As adsorbent hydrophilicity increases, protein adsorption monotonically decreases because the energetic cost of surface dehydration increases, ultimately leading to no protein adsorption near an adsorbent water wettability (surface energy) characterized ...

This opinion identifies inconsistencies in the generally-accepted surface biophysics involved in contact activation of blood-plasma coagulation, reviews recent experimental work aimed at resolving inconsistencies, and concludes that this standard paradigm requires substantial revision to accommodate new experimental observations. Foremost among these new findings is that surfacecatalyzed conversion of the blood zymogen factor XII (FXII, Hageman factor) to the enzyme FXIIa ( , a.k.a. autoactivation) is not specific for anionic surfaces, as proposed by the standard paradigm. Furthermore, it is found that surface activation is moderated by the protein composition of the fluid phase in which FXII autoactivation occurs by what appears to be a protein adsorption-competition effect. Both of these findings argue against the standard view that contact activation of plasma coagulation is potentiated by assembly of activation-complex proteins (FXII, FXI, prekallikrein, and high-molecular-weight kininogen) directly onto activating surfaces (procoagulants) through specific protein/surface interactions. These new findings supplement the observation that adsorption behavior of FXII and FXIIa is not remarkably different from a wide variety of other blood proteins surveyed. Similarity in adsorption properties further undermines the idea that FXII and/or FXIIa are distinguished from other blood proteins by unusual adsorption properties resulting in chemically-specific interactions with activating anionic surfaces.

Time-dependent phenotypic response of a model osteoblast cell line (hFOB 1.19, ATCC, CRL-11372) to substrata with varying surface chemistry and topography is reviewed within the context of extant cell-adhesion theory. Cell-attachment and proliferation kinetics are compared using morphology as a leading indicator of cell phenotype. Expression of (α 2 , α 3 , α 4 , α 5 , α v , β 1 and β 3 ) integrins, vinculin, as well as secretion of osteopontin and type I collagen supplement this visual assessment of hFOB growth. It is concluded that significant cell-adhesion events -contact, attachment, spreading, and proliferation -are similar on all surfaces, independent of substratum surface chemistry/energy. However, this sequence of events is significantly delayed and attenuated on hydrophobic (poorly water-wettable) surfaces exhibiting characteristically low-attachment efficiency and long induction periods before cells engage in an exponential-growth phase. Results suggest that a 'time-cell-substratum compatibility-superposition-principle' is at work wherein similar bioadhesive outcomes can be ultimately achieved on all surface types with varying hydrophilicity, but the time required to arrive at this outcome increases with decreasing cellsubstratum compatibility. Genomic and proteomic tools offer unprecedented opportunity to directly measure changes in the cellular machinery that lead to observed cell responses to different materials. But for the purpose of measuring structure-property relationships that can guide biomaterial development, genomic/proteomic tools should be applied early in the adhesion/spreading process before cells have an opportunity to significantly remodel the cell-substratum interface, effectively erasing cause-and-effect relationships between cell cell-substratum compatibility and substratum properties.Impact Statement-This review quantifies relationships among cell phenotype, substratum surface chemistry/energy, topography, and cell-substratum contact time for the model osteoblast cell