In recent years, the use of microfabrication techniques has allowed biomaterials studies which were originally carried out at larger length scales to be miniaturized as so‐called “on‐chip” experiments. These miniaturized experiments have a range of advantages which have led to an increase in their popularity. A range of biomaterial shapes and compositions are synthesized or manufactured on chip. Moreover, chips are developed to investigate specific aspects of interactions between biomaterials and biological systems. Finally, biomaterials are used in microfabricated devices to replicate the physiological microenvironment in studies using so‐called “organ‐on‐chip,” “tissue‐on‐chip” or “disease‐on‐chip” models, which can reduce the use of animal models with their inherent high cost and ethical issues, and due to the possible use of human cells can increase the translation of research from lab to clinic. This review gives an overview of recent developments at the interface between microfabrication and biomaterials science, and indicates potential future directions that the field may take. In particular, a trend toward increased scale and automation is apparent, allowing both industrial production of micron‐scale biomaterials and high‐throughput screening of the interaction of diverse materials libraries with cells and bioengineered tissues and organs.

In recent years, synthetic calcium phosphate (CaP) ceramics have emerged as an alternative to bone grafts in the treatment of large critical-sized bone defects. To successfully substitute for bone grafts, materials must be osteoinductive, that is, they must induce osteogenic differentiation and subsequent bone formation in vivo. Although a set of osteoinductive CaP ceramics has been developed, the precise biological mechanism by which a material directs cells toward osteogenesis and the role of individual chemical and physical properties in this mechanism remain incompletely understood. Here, we used proteomics to compare serum protein adsorption to two CaP ceramics with different osteoinductive potential, namely an osteoinductive β-tricalcium phosphate (TCP) and a non-osteoinductive hydroxyapatite (HA). Moreover, we analyzed the protein profiles of human mesenchymal stromal cells (hMSCs) cultured on these two ceramics. The serum protein adsorption experiments in the absence of cells highlighted the proteins that are highly abundant in the serum and/or have a high affinity to CaP. The extent of adsorption was suggested to be affected by the available surface area for binding and by the ion exchange dynamics on the surface. Several proteins were uniquely expressed by hMSCs on TCP and HA surfaces. Proteins identified as enriched on TCP were involved in processes related to wound healing, cell proliferation, and the production of extracellular matrix. On the other hand, proteins that were enriched on HA were involved in processes related to protein production, translation, localization, and secretion. In addition, we performed a separate proteomics analysis on TCP, HA, and two biphasic calcium phosphates with known osteoinductive potential and performed a clustering analysis on a combination of a set of proteins found to be enriched on osteoinductive materials with a set of proteins already known to be involved in osteogenesis. This yielded two protein networks potentially involved in the process of osteoinduction – one consisting of collagen fragments and collagen-related enzymes and a second consisting of endopeptidase inhibitors and regulatory proteins. The results of this study show that protein profiling can be a useful tool to help understand the effect of biomaterial properties on the interactions between a biomaterial and a biological system. Such understanding will contribute to the design and development of improved biomaterials for (bone) regenerative therapies.

Microcapsules are a key class of microscale materials with applications in areas ranging from personal care to biomedicine, and with increasing potential to act as extracellular matrix (ECM) models of hollow organs, tissues, or biomolecular condensates. Such capsules are conventionally generated from non‐ECM materials including synthetic polymers. Here, robust microcapsules with controllable shell thickness from physically‐ and enzymatically‐crosslinked gelatin are fabricated, and a core–shell architecture is achieved by exploiting a liquid–liquid phase‐separated aqueous system in a one‐step microfluidic process. Microfluidic mechanical testing reveals that the mechanical robustness of thicker‐shell capsules could be controlled through modulation of the shell thickness. Furthermore, the microcapsules demonstrate environmentally‐responsive deformation, including buckling driven by osmosis and external mechanical forces. A sequential release of cargo species is obtained through the degradation of the capsules. Stability measurements show the capsules are stable at 37 °C for more than 2 weeks. Finally, through gel–sol transition, microgels function as precursors for the formation of all‐aqueous liquid–liquid phase‐separated systems that are two‐phase or multiphase. These smart capsules that can undergo phase transition are promising models of hollow biostructures, microscale drug carriers, and building blocks or compartments for active soft materials and robots.

Due to their natural tendency to self-assemble, proteins and peptides are important components for organic nanotechnology. One particular class of peptides of recent interest is those that form amyloid fibrils, as this self-assembly results in extremely strong, stable quasi-one-dimensional structures which can be used to organise a wide range of cargo species including proteins and oligonucleotides. However, assembly of peptides already conjugated to proteins is limited to cargo species that do not interfere sterically with the assembly process or misfold under the harsh conditions often used for assembly. Therefore, a general method is needed to conjugate proteins and other molecules to amyloid fibrils after the fibrils have self-assembled. Here we have designed an amyloidogenic peptide based on the TTR105-115 fragment of transthyretin to form fibrils that display an alkyne functionality, important for bioorthogonal chemical reactions, on their surface. The fibrils were formed and reacted both with an azide-containing amino acid and with an azide-functionalised dye by the Huisgen cycloaddition, one of the class of “click” reactions. Mass spectrometry and total internal reflection fluorescence optical microscopy were used to show that peptides incorporated into the fibrils reacted with the azide while maintaining the structure of the fibril. These click-functionalised amyloid fibrils have a variety of potential uses in materials and as scaffolds for bionanotechnology. Although previous studies have produced peptides that can both form amyloid fibrils and undergo “click”-type reactions, this is the first example of amyloid fibrils that can undergo such a reaction after they have been formed. Our approach has the advantage that self-assembly takes place before click functionalization rather than pre-functionalised building blocks self-assembling. Therefore, the molecules used to functionalise the fibril do not themselves have to be exposed to harsh, amyloid-forming conditions. This means that a wider range of proteins can be used as ligands in this process. For instance, the fibrils can be functionalised with a green fluorescent protein that retains its fluorescence after it is attached to the fibrils, whereas this protein loses its fluorescence if it is exposed to the conditions used for aggregation.

Deposition of minerals, particularly calcium phosphates such as hydroxyapatite, is an important process in the formation of hard tissues such as bone. Herein, a new, affordable, straightforward and nondestructive method based on complex capacitance spectroscopy, an application of electrochemical impedance spectroscopy, is described which allows repeated and real‐time measurements of the same sample throughout the calcium phosphate deposition process. In contrast with end‐point assays which require large numbers of samples to obtain useful time‐course data, this method allows the kinetics of deposition to be measured using a single sample by measuring the impedance of a pair of interdigitated electrodes at a range of frequencies as the layer of mineral is deposited. Changes in the complex capacitance curve over time with deposition can be compared with images of the coating deposited on model substrates, and show different behavior depending on the composition of the coating and the conditions of deposition.

Biomimetic in vitro models to study tissue (patho)physiology are increasingly important to complement or replace animal experiments. In recent years, various organ‐on‐chip models have been developed, resembling specific structural and functional aspects of human tissues and organs. This study presents a novel human bone defect‐on‐a‐chip (BDOC) model, aiming to recapitulate selected key processes during the early post‐injury phase of bone healing, incorporating bone graft substitutes. Such models minimize cell and reagent use, lowering experimental costs. Additionally, they provide an alternative to animal models. Using human cells provides translatable data unaffected by interspecies differences, narrowing the gap between proof‐of‐concept and clinical application. Moreover, these models offer excellent observational capability, enabling high‐resolution analysis of cellular behavior. The BDOC features two diverging host bone‐mimicking side compartments defining a triangular defect‐like inner chamber with different gap sizes. Over 21 days, human mesenchymal stem/stromal cells (HMSCs) and human primary macrophages are co‐cultured in the BDOC together with calcium phosphate microparticles. The HMSCs’ gap size‐dependent migration, osteogenic differentiation, and mineralization are assessed inside the inner chamber. The HMSCs travel from the side compartments to the defect‐like area, express key osteogenic markers, and deposit mineral. Similar models could help develop biomaterial‐based bone regenerative therapies one day.