Supramolecular peptide nano-assemblies for cancer diagnosis and therapy: from molecular design to material synthesis and function-specific applications.

Peptide molecule has high bioactivity, good biocompatibility, and excellent biodegradability. In addition, it has adjustable amino acid structure and sequence, which can be flexible designed and tailored to form supramolecular nano-assemblies with specific biomimicking, recognition, and targeting properties via molecular self-assembly. These unique properties of peptide nano-assemblies made it possible for utilizing them for biomedical and tissue engineering applications. In this review, we summarize recent progress on the motif design, self-assembly synthesis, and functional tailoring of peptide nano-assemblies for both cancer diagnosis and therapy. For this aim, firstly we demonstrate the methodologies on the synthesis of various functional pure and hybrid peptide nano-assemblies, by which the structural and functional tailoring of peptide nano-assemblies are introduced and discussed in detail. Secondly, we present the applications of peptide nano-assemblies for cancer diagnosis applications, including optical and magnetic imaging as well as biosensing of cancer cells. Thirdly, the design of peptide nano-assemblies for enzyme-mediated killing, chemo-therapy, photothermal therapy, and multi-therapy of cancer cells are introduced. Finally, the challenges and perspectives in this promising topic are discussed. This work will be useful for readers to understand the methodologies on peptide design and functional tailoring for highly effective, specific, and targeted diagnosis and therapy of cancers, and at the same time it will promote the development of cancer diagnosis and therapy by linking those knowledges in biological science, nanotechnology, biomedicine, tissue engineering, and analytical science.

The design and biomedical applications of self-assembled two-dimensional organic biomaterials.

The design and applications of some inorganic two-dimensional (2D) nanomaterials such as graphene, graphyne, and borophene have been widely studied in recent years. Meanwhile, it has been noticed that self-assembling two-dimensional organic biomaterials (2DOBMs) including films, membranes, nanosheets, nanoribbons, grids, arrays, and lattices based on various biomolecules also exhibited promising structures, functions, and applications. The in-depth studies on the self-assembly formation, structural and functional tailoring of 2DOBMs open new avenues for the next generation of novel nanomaterials with adjustable structure and functions, which would further promote the applications of 2DOBMs in materials science, nanodevices, energy and environmental science, biomedicine, tissue engineering, and analytical science. In this review, we summarize important information on the basic principles to fabricate self-assembling 2DOBMs based on peptides, proteins, DNA, RNA, viruses, and other biopolymers. The potential strategies and techniques for tailoring and controlling the structures and functions of 2DOBMs are presented and discussed further. The function-specific biomedical applications of 2DOBMs in biosensors, biomimetic mineralization, cell growth, drug/gene delivery, and bioimaging are also highlighted.

Nanoconfinement and Sansetsukon-like Nanocrawling Govern Fibrinogen Dynamics and Self-Assembly on Nanostructured Polymeric Surfaces.

Surface nanostructures are increasingly more employed for controlled protein assembly on functional nanodevices, in nanobiotechnology, and in nanobiomaterials. However, the mechanism and dynamics of how nanostructures induce order in the adsorbed protein assemblies are still enigmatic. Here, we use single-molecule mapping by accumulated probe trajectories and complementary atomic force microscopy to shed light on the dynamic of in situ assembly of human plasma fibrinogen (HPF) adsorbed on nanostructured polybutene-1 (PB-1) and nanostructured polyethylene (PE) surfaces. We found a distinct lateral heterogeneity of HPF-polymer nanostructure interface (surface occupancy, residence time, and diffusion coefficient) that allow identifying the interplay between protein topographical nanoconfinement, protein diffusion mechanism, and ordered protein self-assembly. The protein diffusion analysis revealed high-diffusion polarization without correlation to the anisotropic friction characteristic of the polymer surfaces. This suggests that HPF molecules confined on the nanosized PB-1 needle crystals and PE shish-kebab crystals, respectively, undergo partial detachment and diffuse via a Sansetsukon-like nanocrawling mechanism. This mechanism is based on the intrinsic flexibility of HPF in the coiled-coil regions. We conclude that nanostructured surfaces that encourage this characteristic surface mobility are more likely to lead to the formation of ordered protein assemblies and may be useful for advanced nanobiomaterials.

Methane production in microbial reverse-electrodialysis methanogenesis cells (MRMCs) using thermolytic solutions.

The utilization of bioelectrochemical systems for methane production has attracted increasing attention, but producing methane in these systems requires additional voltage to overcome large cathode overpotentials. To eliminate the need for electrical grid energy, we constructed a microbial reverse-electrodialysis methanogenesis cell (MRMC) by placing a reverse electrodialysis (RED) stack between an anode with exoelectrogenic microorganisms and a methanogenic biocathode. In the MRMC, renewable salinity gradient energy was converted to electrical energy, thus providing the added potential needed for methane evolution from the cathode. The feasibility of the MRMC was examined using three different cathode materials (stainless steel mesh coated with platinum, SS/Pt; carbon cloth coated with carbon black, CC/CB; or a plain graphite fiber brush, GFB) and a thermolytic solution (ammonium bicarbonate) in the RED stack. A maximum methane yield of 0.60 ± 0.01 mol-CH4/mol-acetate was obtained using the SS/Pt biocathode, with a Coulombic recovery of 75 ± 2% and energy efficiency of 7.0 ± 0.3%. The CC/CB biocathode MRMC had a lower methane yield of 0.55 ± 0.02 mol-CH4/mol-acetate, which was twice that of the GFB biocathode MRMC. COD removals (89-91%) and Coulombic efficiencies (74-81%) were similar for all cathode materials. Linear sweep voltammetry and electrochemical impedance spectroscopy tests demonstrated that cathodic microorganisms enhanced electron transfer from the cathode compared to abiotic controls. These results show that the MRMC has significant potential for production of nearly pure methane using low-grade waste heat and a source of waste organic matter at the anode.

Highly Stretchable Double Network Ionogels for Monitoring Physiological Signals and Detecting Sign Language.

At the heart of the non-implantable electronic revolution lies ionogels, which are remarkably conductive, thermally stable, and even antimicrobial materials. Yet, their potential has been hindered by poor mechanical properties. Herein, a double network (DN) ionogel crafted from 1-Ethyl-3-methylimidazolium chloride ([Emim]Cl), acrylamide (AM), and polyvinyl alcohol (PVA) was constructed. Tensile strength, fracture elongation, and conductivity can be adjusted across a wide range, enabling researchers to fabricate the material to meet specific needs. With adjustable mechanical properties, such as tensile strength (0.06-5.30 MPa) and fracture elongation (363-1373%), this ionogel possesses both robustness and flexibility. This ionogel exhibits a bi-modal response to temperature and strain, making it an ideal candidate for strain sensor applications. It also functions as a flexible strain sensor that can detect physiological signals in real time, opening doors to personalized health monitoring and disease management. Moreover, these gels' ability to decode the intricate movements of sign language paves the way for improved communication accessibility for the deaf and hard-of-hearing community. This DN ionogel lays the foundation for a future in which e-skins and wearable sensors will seamlessly integrate into our lives, revolutionizing healthcare, human-machine interaction, and beyond.

Preparation, function, and safety evaluation of a novel degradable dermal filler, the cross-linked poly-γ-glutamic acid hydrogel particles.

Poly-γ-glutamic acid (PGA) is a naturally degradable hydrophilic linear microbial polymer with moisturizing, immunogenic, cross-linking, and hydrogel water absorption properties similar to hyaluronic acid, a biomaterial that is commonly used as a dermal filler. To explore the development feasibility of cross-linked PGA as a novel dermal filler, we studied the local skin response to PGA fillers and the effect of various cross-linking preparations on the average longevity of dermal injection. Injection site inflammation and the formation of collagen and elastin were also determined. PGA hydrogel particles prepared using 28% PGA and 10% 1,4-butanediol diglycidyl ether showed optimal filler properties, resistance to moist heat sterilization, and an average filling longevity of 94.7 ± 61.6 days in the dermis of rabbit ears. Local redness and swelling due to filler injection recovered within 14.2 ± 3.6 days. Local tissue necrosis or systemic allergic reactions were not observed, and local collagen formation was promoted. Preliminary results suggested that dermal injection of cross-linked PGA particles appeared safe and effective, suggesting that cross-linked PGA particles could be developed as a new hydrogel dermal filler.

Expression of phosphophoryn is sufficient for the induction of matrix mineralization by mammalian cells.

Mineralized tissues such as dentin and bone assemble extracellular matrices uniquely rich in a variety of acidic phosphoproteins. Although these proteins are presumed to play a role in the process of biomineralization, key questions regarding the nature of their contributions remain unanswered. First, it is not known whether highly phosphorylated proteins alone can induce matrix mineralization, or whether this activity requires the involvement of other bone/dentin non-collagenous proteins. Second, it remains to be established whether the protein kinases that phosphorylate these acidic proteins are unique to cells responsible for producing mineralized tissues. To begin to address these questions, we consider the case of phosphophoryn (PP), due to its high content of phosphate, high affinity for Ca(2+), and its potential role in hydroxyapatite nucleation. We have created a model system of biomineralization in a cellular environment by expressing PP in NIH3T3 fibroblasts (which do not produce a mineralized matrix); as a positive control, PP was expressed in MC3T3-E1 osteoblastic cells, which normally mineralize their matrices. We show that expression of PP in NIH3T3 cells is sufficient for the induction of matrix mineralization. In addition, assessment of the phosphorylation status of PP in these cells reveals that the transfected NIH3T3 cells are able to phosphorylate PP. We suggest that the phosphorylation of PP is essential for mineral formation. The principle goal of this study is to enrich the current knowledge of mineralized tissue phosphorylation events by analyzing them in the context of a complete cellular environment.

Necessity of direct energy and ammonium recovery for carbon neutral municipal wastewater reclamation in an innovative anaerobic MBR-biochar adsorption-reverse osmosis process.

With the speedy evolution of global climate change and water shortage, there is a growing need for the energy and carbon neutral wastewater reclamation technology. To tackle this challenge, an innovative anaerobic membrane bioreactor (AnMBR)-biochar adsorption-RO process was developed for reclaiming municipal wastewater to high-grade product water with the aims for achieving the energy and carbon neutrality. It was found that about 95.6% of influent COD was removed by AnMBR with direct generation of biomethane, while ammonium-N in AnMBR permeate was fully recovered through biochar adsorption. The effluent from biochar adsorber with significantly lowered divalent ions concentrations was further reclaimed by RO at reduced cost and energy consumption. The energy demand and the total carbon emissions in the proposed process were estimated to be 0.50 kWh/m3 and 633 g CO2e/ m3 against 0.86 kWh/m3 and 1101 g CO2e/ m3 in the current conventional activated sludge (CAS)-microfiltration-RO process. It was further shown that the ammonium recovery via biochar adsorption could offset about 0.503 kWh/m3 that was originally utilized for chemically producing recovered ammonia by the Haber-Bosch method, equivalent to a carbon offsetting of 498 g CO2e/m3, leading to a net carbon emission of 135 CO2e/m3 in the proposed process, which was only about 12% of that in the current CAS-MF-RO process. These suggested that a carbon-neutral municipal wastewater reclamation might be achievable through concurrent carbon reduction and offsetting, while carbon offsetting via ammonia recovery appeared to be a game-changer towards the carbon-neutral operation. Consequently, it is expected that this study can shed lights on how energy- and carbon-neutrality would be achieved by innovating municipal wastewater reclamation technology.

When 2D nanomaterials meet biomolecules: design strategies and hybrid nanostructures for bone tissue engineering.

2D nanomaterials show great potential in biomedical applications due to their unique physical and chemical surface properties. This review includes typical 2D nanomaterials used in bone tissue engineering (BTE), such as graphene oxide, hexagonal boron nitride, molybdenum disulfide, black phosphorus, and MXenes. Moreover, the construction methods of BTE materials with 2D nanosheets are analyzed. Before designing a BTE material, it is essential to understand the relationship between the material structure and properties. Notably, 2D nanomaterials can be hybridized with biomaterials, such as polypeptides, proteins, and polysaccharides, to improve biocompatibility and host responses. The effects of the surface properties and size of 2D nanomaterials on cellular behavior, gene expression, antibacterial properties, and cytotoxicity in BTE applications are also discussed. This work provides new design ideas and directions for constructing 2D nanomaterial-based BTE scaffolds.

The antimicrobial effect of calcium-doped titanium is activated by fibrinogen adsorption.

Directly targeting bacterial cells is the present paradigm for designing antimicrobial biomaterial surfaces and minimizing device-associated infections (DAIs); however, such pathways may create problems in tissue integration because materials that are toxic to bacteria can also be harmful to mammalian cells. Herein, we report an unexpected antimicrobial effect of calcium-doped titanium, which itself has no apparent killing effect on the growth of pathogenic bacteria (Pseudomonas aeruginosa, Pa, ATCC 27853) while presenting strong inhibition efficiency on bacterial colonization after fibrinogen adsorption onto the material. Fine X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy analyses reported calcium-dependent shifts of the binding energy in nitrogen and oxygen involved groups and wavenumbers in the amide I and II bands of the adsorbent fibrinogen, demonstrating that locally delivered calcium can react with the carboxy-terminal regions of the Aα chains and influence their interaction with the N-termini of the Bß chains in fibrinogen. These reactions facilitate the exposure of the antimicrobial motifs of the protein, indicating the reason for the surprising antimicrobial efficacy of calcium-doped titanium. Since protein adsorption is an immediate intrinsic step during the implantation surgery, this finding may shift the present paradigm on the design of implantable antibacterial biomaterial surfaces.

Possible role of DMP1 in dentin mineralization.

Dentin Matrix Protein 1 (DMP1), the essential noncollagenous proteins in dentin and bone, is believed to play an important role in the mineralization of these tissues, although the mechanisms of its action are not fully understood. To gain insight into DMP1 functions in dentin mineralization we have performed immunomapping of DMP1 in fully mineralized rat incisors and in vitro calcium phosphate mineralization experiments in the presence of DMP1. DMP1 immunofluorescene was localized in peritubular dentin (PTD) and along the dentin-enamel boundary. In vitro phosphorylated DMP1 induced the formation of parallel arrays of crystallites with their c-axes co-aligned. Such crystalline arrangement is a hallmark of mineralized collagen fibrils of bone and dentin. Interestingly, in DMP1-rich PTD, which lacks collagen fibrils, the crystals are organized in a similar manner. Based on our findings we hypothesize, that in vivo DMP1 controls the mineral organization outside of the collagen fibrils and plays a major role in the mineralization of PTD.

Primary structure and phosphorylation of dentin matrix protein 1 (DMP1) and dentin phosphophoryn (DPP) uniquely determine their role in biomineralization.

The SIBLING (small integrin-binding ligand N-linked glycoproteins) family is the major group of noncollagenous proteins in bone and dentin. These extremely acidic and highly phosphorylated extracellular proteins play critical roles in the formation of collagenous mineralized tissues. Whereas the lack of individual SIBLINGs causes significant mineralization defects in vivo, none of them led to a complete cessation of mineralization suggesting that these proteins have overlapping functions. To assess whether different SIBLINGs regulate biomineralization in a similar manner and how phosphorylation impacts their activity, we studied the effects of two SIBLINGs, dentin matrix protein 1 (DMP1) and dentin phosphophoryn (DPP), on mineral morphology and organization in vitro. Our results demonstrate distinct differences in the effects of these proteins on mineralization. We show that phosphorylation has a profound effect on the regulation of mineralization by both proteins. Specifically, both phosphorylated proteins facilitated organized mineralization of collagen fibrils and phosphorylated DMP1-induced formation of organized mineral bundles in the absence of collagen. In summary, these results indicate that the primary structure and phosphorylation uniquely determine functions of individual SIBLINGs in regulation of mineral morphology and organization.

MoS2 QDs/8-Armed Poly(Ethylene Glycol) Fluorescence Sensor for Three Nitrotoluenes (TNT) Detection.

In this work, ammonia cross-linked 8-armed polyethylene glycol hydrogel material was successfully synthesized and used as a template for synthesizing nanoparticles with fluorescent properties. The 8-armed polyethylene glycol hydrogel template was used to prepare molybdenum disulfide quantum dots (MoS2 QDs). The ammonium tetrathiomolybdate functioned as a molybdenum source and hydrazine hydrate functioned as a reducing agent. The fluorescence properties of the as-prepared MoS2 QDs were investigated. The bursting of fluorescence caused by adding different concentrations of explosive TNT was studied. The study indicated that the synthesized MoS2 QDs can be used for trace TNT detection with a detection limit of 6 nmol/L and a detection range of 16-700 nmol/L. Furthermore, it indicated that the fluorescence-bursting mechanism is static bursting.

One-Pot, In-Situ Synthesis of 8-Armed Poly(Ethylene Glycol)-Coated Ag Nanoclusters as a Fluorescent Sensor for Selective Detection of Cu2.

Fluorescent nanomaterials, such as quantum dots, have developed rapidly in recent years and have been significantly developed. Herein, we demonstrate a facile, one-pot, and in-situ synthesis strategy to obtain fluorescent silver nanoclusters (AgNCs) coated with eight-armed poly (ethylene glycol) polymers (8PEG-AgNCs) via a direct gel-mediated process. During the synthesis, ammonium (NH3) served as the crosslinker for the gel formation via a amine-type Michael addition reaction. This hydrogel can be used as a template to synthesize AgNCs using its volume-limiting effect. The in-situ generation of AgNCs takes place inside the nanocages of the formed gels, which guarantees the homogenous distribution of AgNCs in the gel matrix, as well as the efficient coating of PEG on the nanoclusters. After the degradation of gels, the released 8PEG-AgNCs nanohybrids showed strong blue fluorescence and exhibited long-term stability in aqueous solution for nearly one year. Results showed that the fabricated sensor revealed excellent fluorescent sensitivity for the selective detection of Cu2+ with a detection limit of 50 nM and a wide linear detection range of 5-100 µM. It is proposed that the greater cross-linking density leads to smaller gel pores and allows the synthesis of AgNCs with fluorescent properties. These results indicate that this novel hydrogel with certain biodegradation has the potential to be applied as a fluorescent sensor for catalytic synthesis, fluorescence tracing in cells, and fluorescence detection fields. Meanwhile, the novel design principle has a certain versatility to accelerate the development and application of other kinds of metal nanoclusters and quantum dots.

Evaluating the performance of inorganic draw solution concentrations in an anaerobic forward osmosis membrane bioreactor for real municipal sewage treatment.

Sewage can become a valuable source if its treatment is re-oriented for recovery. An anaerobic forward osmosis membrane bioreactor (AnOMBR) was developed for real municipal sewage treatment to investigate performance, biogas production, flux change and mixed liquor characteristics. The AnOMBR had a good treatment capacity with removal ratio of chemical oxygen demand, ammonia nitrogen, total nitrogen and total phosphorus more than 96%, 88%, 89% and almost 100%. Although high DS concentration increased the initial flux, it caused rapid decline and poor recoverability of FO membrane flux. Low DS concentration led to too long hydraulic retention time, thus resulting in a low reactor efficiency. Additionally, it was observed that salt, protein, polysaccharide and humic acid were all accumulated in the reactor, which was not conducive to stable long-term operation. Based on the characteristics of membrane fouling, salt accumulation and AnOMBR performance, the optimal DS of 1 M NaCl solution was selected.

Membrane autopsy deciphering keystone microorganisms stubborn against online NaOCl cleaning in a full-scale MBR.

The knowledge about membrane biofouling evolution in full-scale membrane bioreactor (MBR) applications is quite lacking, notwithstanding a few lab-scale investigations. For the first time, this study elaborated the effect of online NaOCl cleaning on the dynamic development of membrane biofilm microbiota during long-term operation of a large-scale MBR for municipal wastewater treatment (40,000 m3/d). Four times of membrane autopsies were conducted during 160 days operation to scrutinize the microbial community and concomitant organic foulants. The transmembrane pressure difference (TMP) development revealed limited effect of 30 min online NaOCl cleaning on long-term biofouling removal. NaOCl not only altered the structure of biofilm communities but also increased the richness and evenness on early fouling stages. Meanwhile, network analysis revealed the keystone taxa f_Comamonadaceae that played key roles in stabilizing community structure and developing anti-cleaning and irreversible fouling propensity of the biofilm. NaOCl cleaning also impacted the evolving of keystone taxa by intensifying the competition between the dominated taxa f_Moraxellaceae and other species during early fouling stages. Furthermore, the succession of the biofilm microbiota synchronously accelerated the TMP increase and the accumulation of organic foulants including polysaccharides, aromatic proteins and soluble microbial products during biofilm maturation. These identified key stubborn foulants shed light on limitations of current online NaOCl cleaning and provide guidance to optimize the efficiency of online chemical cleaning protocols in full-scale MBR operations.

Reduced graphene oxide (rGO) hybridized hydrogel as a near-infrared (NIR)/pH dual-responsive platform for combined chemo-photothermal therapy.

For personalized cancer treatment, developing smart biomaterials with multiple biological functions is indispensable in nanomedicine fields. In this work, we developed a highly efficient near-infrared- (NIR-) and pH-responsive carboxymethyl chitosan-functionalized reduced graphene oxide/aldehyde functionalized poly (ethylene glycol) (CMC-rGO/CHO-PEG) hydrogel, which exhibits outstanding delivery performance of antitumor drug, doxorubicin hydrochloride (DOX). CMC was functionalized on the GO nanosheets via a controllable approach in order to achieve strong NIR absorption property and good distribution of rGO. The intercalation effect of CMC-rGO complex improved rGO distribution in the 3D hydrogel, contributing to the enhanced photothermal performance of CMC-rGO/CHO-PEG hydrogel. Furthermore, potential utilization of these CMC-rGO/CHO-PEG hydrogel for drug loading was studied, which provided pH-sensitive release of DOX payload. Particularly, DOX could be released in a more efficient way under acidic environment (pH = 6.5) than that under physiological environment (pH = 7.4). Therefore, this rGO hybridized PEG hydrogel holds strategic potential as a novel drug release platform for combined chem-photothermal therapy.

A novel operational strategy to enhance wastewater treatment with dual-anode assembled microbial desalination cell.

This study introduced a novel dual-anode assembled microbial desalination cell to enhance the performance of domestic wastewater treatment. Two parallel units were fabricated with two anodes and one cathode, which is separated by two ion exchange membrane stacks. A hollow fiber membrane module was inserted in the cathode to intercept suspended solids and microbes. Based on preliminary experiments where synthetic wastewater was utilized, anode hydraulic retention time of 10 h and cathode aeration rate of 0.16 m3/h were chosen as the operating conditions. By innovatively connecting four membrane stacks in cascades, which multiplied flow rate without adding extra circulation pumps, the desalination rate of the system was improved 214.8% compared with single membrane stack mode. When modified domestic wastewater was applied, the average removal efficiencies of chemical oxygen demand, ammonia nitrogen, total nitrogen and total phosphorous reached 96.9%, 99.0%, 98.0% and 98.3%, respectively.

Enhancing extracellular electron transfer efficiency and bioelectricity production by vapor polymerization Poly (3,4-ethylenedioxythiophene)/MnO2 hybrid anode.

Electron transfer efficiency in electroactive biofilm is the limiting factor for bioelectricity output of bioelectrochemical system. Here, carbon felt (CF) is coated with manganese dioxide (MnO2) which acts as electron mediator in electroactive biofilm. A wrapping layer of conducting Poly 3,4-ethylenedioxythiophene is developed to protect the MnO2 and enhance electron transfer efficiency of MnO2 mediator. The hybrid bioanode (PEDOT/MnO2/CF bioanode) delivered the highest electron transfer efficiency (6.3 × 10-9 mol cm-2 s-1/2) and the highest capacitance of 4.78 F, much higher than bare CF bioanode (1.50 ±â€¯0.04 × 10-9 mol cm-2 s-1/2 and 0.42 F). As a result, microbial fuel cells could produce a maximum power density of 1534 ±â€¯13 mW m-2, approximately 57.7% higher than that with the bare carbon felt anode (972 ±â€¯21 mW m-2). Possible mechanisms are proposed to help understanding the different function of the PEDOT and MnO2 on the anodic layer. This study introduces an effective method for the fabrication of high performance anode.

Controlling Protein Adsorption through Nanostructured Polymeric Surfaces.

The initial host response to healthcare materials' surfaces after implantation is the adsorption of proteins from blood and interstitial fluids. This adsorbed protein layer modulates the biological/cellular responses to healthcare materials. This stresses the significance of the surface protein assembly for the biocompatibility and functionality of biomaterials and necessitates a profound fundamental understanding of the capability to control protein-surface interactions. This review, therefore, addresses this by systematically analyzing and discussing strategies to control protein adsorption on polymeric healthcare materials through the introduction of specific surface nanostructures. Relevant proteins, healthcare materials' surface properties, clinical applications of polymer healthcare materials, fabrication methods for nanostructured polymer surfaces, amorphous, semicrystalline and block copolymers are considered with a special emphasis on the topographical control of protein adsorption. The review shows that nanostructured polymer surfaces are powerful tools to control the amount, orientation, and order of adsorbed protein layers. It also shows that the understanding of the biological responses to such ordered protein adsorption is still in its infancy, yet it has immense potential for future healthcare materials. The review, which is-as far as it is known-the first one discussing protein adsorption on nanostructured polymer surfaces, concludes with highlighting important current research questions.