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Systemically circulating microbubbles are used as contrast agents to aid both drug targeting and delivery using ultrasound. Exploiting their acoustic behaviour in small diameter vessels is critical for both applications, but the highly controlled experiments required to support this are not possible in vivo and challenging in vitro. Experimental platforms with small diameter channels (below 200 microns) are not readily available nor able to represent vascular geometries, leaving the existence and extent of microbubble-microvessel interactions incompletely defined. In this work we present a 3D-printed microchannel platform using tissue-mimicking hydrogels featuring radii down to 75 microns. We demonstrate application to study microbubble behaviour via acoustic backscatter under controlled environments in physiologically-relevant conditions.

[EN] The ideal bone substitute material should be mechanically strong, biocompatible with a resorption rate matching the rate of new bone formation. Brushite (dicalcium phosphate dihydrate) cement is a promising bone substitute material but with limited resorbability and mechanical properties. To improve the resorbability and mechanical performance of brushite cements, we incorporated gypsum (calcium sulfate dihydrate) and diazonium-treated polyglactin fibers which are well-known for their biocompatibility and bioresorbability. Here we show that by combining brushite and gypsum, we were able to fabricate biocompatible composite cements with high fracture toughness (0.47 MPa center dot m1/2) and a resorption rate that matched the rate of new bone formation. Adding functionalized polyglactin fibers to this composite cement further improved the fracture toughness up to 1.00 MPa center dot m1/2. XPS and SEM revealed that the improvement in fracture toughness is due to the strong interfacial bonding between the functionalized fibers and the cement matrix. This study shows that adding gypsum and functionalized polyglactin fibers to brushite cements results in composite biomaterials that combine high fracture toughness, resorbability, and biocompatibility, and have great potential for bone regeneration., We thank Dr. David Liu, for assistance with the mineral characterization and McGill University's Facility for Electron Microscopy Research (FEMR) for assisting in many ways with this work. This study was supported by the Libyan Ministry of Education and Scientific Research (H. M.) , the Canadian Foundation for Innovation (CFI, F.T.) , NSERC Discovery Grants RGPIN-2019-04340 (F.T.) , "Le Reseau de recherche en sante buccodentaire et osseuse" (RSBO) , and the Canada Research Chair program (F.T. and M.C.) . MS-S acknowledges support from the UK Engineering and Physical Sciences Research Council (EPSRCEP/P001114/1) .

[EN] Collagen hydrogels are among the most well-studied platforms for drug delivery and in situ tissue engineering, thanks to their low cost, low immunogenicity, versatility, biocompatibility, and similarity to the natural extracellular matrix (ECM). Despite collagen being largely responsible for the tensile properties of native connective tissues, collagen hydrogels have relatively low mechanical properties in the absence of covalent cross-linking. This is particularly problematic when attempting to regenerate stiffer and stronger native tissues such as bone. Furthermore, in contrast to hydrogels based on ECM proteins such as fibronectin, collagen hydrogels do not have any growth factor (GF)-specific binding sites and often cannot sequester physiological (small) amounts of the protein. GF binding and in situ presentation are properties that can aid significantly in the tissue regeneration process by dictating cell fate without causing adverse effects such as malignant tumorigenic tissue growth. To alleviate these issues, researchers have developed several strategies to increase the mechanical properties of collagen hydrogels using physical or chemical modifications. This can expand the applicability of collagen hydrogels to tissues subject to a continuous load. GF delivery has also been explored, mathematically and experimentally, through the development of direct loading, chemical cross-linking, electrostatic interaction, and other carrier systems. This comprehensive article explores the ways in which these parameters, mechanical properties and GF delivery, have been optimized in collagen hydrogel systems and examines their in vitro or in vivo biological effect. This article can, therefore, be a useful tool to streamline future studies in the field, by pointing researchers into the appropriate direction according to their collagen hydrogel design requirements., This work was supported by Medical Research Scotland, EPSRC (through a programme grant EP/P001114/1) and a programme of research funded by the Sir Bobby Charlton Foundation. M.S.S. acknowledges support from a grant from the UK Regenerative Medicine Platform 'Acellular/Smart Materials - 3D Architecture' (MR/R015651/1). The graphical abstract was created using BioRender.com.

Brushite cements are promising bone regeneration materials with limited biological and mechanical properties. Here, we engineer a mechanically improved brushite-collagen type I cement with enhanced biological properties by use of chiral chemistry; d- and l-tartaric acid were used to limit crystal growth and increase the mechanical properties of brushite-collagen cements. The impact of the chiral molecules on the cements was examined with Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). A 3-point bend test was utilized to study the fracture toughness, and cell attachment and morphology studies were carried out to demonstrate biocompatibility. XRD and SEM analyses showed that l-, but not d-tartaric acid, significantly restrained brushite crystal growth by binding to the {010} plane of the mineral and increased brushite crystal packing and the collagen interaction area. l-Tartaric acid significantly improved fracture toughness compared to traditional brushite by 30%. Collagen significantly enhanced cell morphology and focal adhesion expression on l-tartaric acid-treated brushite cements.