Implantation of medical devices can result in inflammation. A large library of polymers is screened, and a selection found to promote macrophage differentiation towards pro-or anti-inflammatory phenotypes. The bioinstructive properties of these materials are validated within a rodent model. By identifying novel materials with immune-instructive properties, the relationship between material-immune cell interactions could be investigated, and this offers exciting possibilities to design novel bioinstructive materials that can be used for numerous clinical applications including medical implants.

MicroRNAs are small, noncoding RNAs that function as posttranscriptional modulators of gene expression by binding target mRNAs and inhibiting translation. They are therefore crucial regulators of several biological as well as immunological events. Recently, miR-511-3p has been implicated in the development and differentiation of APCs, such as dendritic cells (DCs), and regulating several human diseases. Interestingly, miR-511-3p is embedded within the human MRC1 gene that encodes the mannose receptor. In this study, we sought to examine the impact of miR-511-3p up-or downregulation on human DC surface phenotype, cytokine profile, immunogenicity (using IDO activity as a surrogate), and downstream T cell polarization. Using gene silencing and a selection of microRNA mimics, we could successfully suppress or induce the expression of miR-511-3p in DCs. Consequently, we show for the first time, to our knowledge, that inhibition and/or overexpression of miR-511-3p has opposing effects on the expression levels of two key C-type lectin receptors, namely the mannose receptor and DC-specific ICAM 3 nonintegrin at protein and mRNA levels, thereby affecting C-type lectin receptor-induced modulation of IDO activity in DCs. Furthermore, we show that downregulation of miR-511-3p drives an anti-inflammatory DC response characterized by IL-10 production. Interestingly, the miR-511-3p low DCs also promoted IL-4 secretion and suppressed IL-17 in cocultures with autologous T cells. Together, our data highlight the potential role of miR-511 in regulating DC function and downstream events leading to Th polarization and immune modulation.

A flow‐focusing microfluidic device is used to produce functionalized monodisperse polymer particles with surface chemistries designed to control bacterial biofilm formation. This is achieved by using molecularly designed bespoke surfactants synthesized via catalytic chain transfer polymerization. This novel approach of using polymeric surfactants, often called surfmers, containing a biofunctional moiety contrasts with the more commonly employed emulsion methods. Typically, the surface chemistry of microparticles are dominated by unwanted surfactants that dilute/mask the desired surface response. Time of flight secondary ion mass spectrometry (ToF‐SIMS) analysis of particles demonstrates that the comb‐graft surfactant is located on the particle surface. Biofilm experiments show how specifically engineered surface chemistries, generated by the surfactants, successfully modulate bacterial attachment to both polymer films, and microparticles. Thus, this paper outlines how the use of designed polymeric surfactants and droplet microfluidics can exert control over both the surface chemistry and size distribution of microparticle materials, demonstrating their critical importance for controlling surface‐cell response.

Design and fabrication of implants that can perform better than autologous bone grafts remain an unmet challenge for the hard tissue regeneration in craniomaxillofacial applications. Here, we report an integrated approach combining additive manufacturing with supramolecular chemistry to develop acellular mineralizing 3D printed scaffolds for hard tissue regeneration. Our approach relies on an elastin-like recombinamer (ELR) coating designed to trigger and guide the growth of ordered apatite on the surface of 3D printed nylon scaffolds. Three test samples including a) uncoated nylon scaffolds (referred to as “Uncoated”), b) ELR coated scaffolds (referred to as “ELR only”), and c) ELR coated and in vitro mineralized scaffolds (referred to as “Pre-mineralized”) were prepared and tested for in vitro and in vivo performance. All test samples supported normal human immortalized mesenchymal stem cell adhesion, growth, and differentiation with enhanced cell proliferation observed in the “Pre-mineralized” samples. Using a rabbit calvarial in vivo model, ‘Pre-mineralized’ scaffolds also exhibited higher bone ingrowth into scaffold pores and cavities with higher tissue-implant integration. However, the coated scaffolds (“ELR only” and “Pre-mineralized”) did not exhibit significantly more new bone formation compared to “Uncoated” scaffolds. Overall, the mineralizing coating offers an opportunity to enhance integration of 3D printed bone implants. However, there is a need to further decipher and tune their immunologic response to develop truly osteoinductive/conductive surfaces.

Wound healing is a complex biological process involving close crosstalk between various cell types.Dysregulation in any of these processes, such as in diabetic wounds, results in chronic non-healing wounds. Fibroblasts are a critical cell type involved in the formation of granulation tissue, essential for effective wound healing. We screened 315 different polymer surfaces to identify candidates which actively drove fibroblasts towards either pro-or anti-proliferative functional phenotypes.Fibroblast-instructive chemistries were identified, which we synthesized into surfactants to fabricate easy to administer microparticles for direct application to diabetic wounds. The pro-proliferative microfluidic derived particles were able to successfully promote neovascularisation, granulation tissue formation and wound closure after a single application to the wound bed. These active novel 3D bio-instructive microparticles show great potential as a route to reducing the burden of chronic wounds.