Systems capable of residing for prolonged periods of time in the gastric cavity have transformed our ability to diagnose and treat patients. Gastric resident systems for drug delivery, ideally need to be: ingestible, be able to change shape or swell to ensure prolonged gastric residence, have the mechanical integrity to withstand the forces associated with gastrointestinal motility, be triggerable to address any side effects, and be drug loadable and release drug over a prolonged period of time. Materials that have been primarily utilized for these applications have been largely restricted to thermoplastics and thermosets. Here we describe a novel set of materials, triggerable tough hydrogels, meeting all these requirement, supported by evaluation in a large animal model and ultimately demonstrate the potential of triggerable tough hydrogels to serve as prolonged gastric resident drug depots. Triggerable tough hydrogels may be applied in myriad of applications, including bariatric interventions, drug delivery, and tissue engineering.
Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells' global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This upregulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cellmaterial interactions and suggest alternative research routes for evaluating biomaterials to improve their design.strontium-releasing biomaterials | human mesenchymal stem cells | microarray analysis | sparse feature selection analysis | mevalonate pathway A n important aim of regenerative medicine is to design smart biomaterials to trigger specific biological responses and enable complex tissue repair (1). Standard in vitro and in vivo testing of such materials usually focuses on assessing the anticipated cell response, often stem cell differentiation to a particular lineage and/or appropriate tissue formation. Although this strategy allows the characterization of specific outcomes, the global cell responses to most biomaterials remain relatively unknown and their mechanisms of action largely unidentified. In comparison with this standard approach, the pharmacology and molecular biology communities have revolutionized their respective fields by taking advantage of unsupervised "-omic" technologies that allow the global biological response to be examined without the inherent bias introduced by predicting particular outcomes. The adoption of comparable hypothesis-generating holistic approaches in the biomaterials communities could stimulate a similar paradigm shift, allowing prospective, rational material design instead of retrospective material evaluation.With more than 2.2 million bone-grafting procedures carried out annually worldwide, the market for smart biomaterials that can be used as functional alternatives to current autogenic and allogenic grafts is significant (2). One biomaterial-based regenerative approach involves the incorporation of biologically active moieties into biomaterials to enhance their bone regeneration properties (3). Strontium ranelate (SrRan) reduces vertebral and nonvertebral fr...
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