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Background/Objectives: Hydrophobic semi-solid or liquid biodegradable polymers have shown unique advantages as injectable matrices for sustained release of a wide range of drugs. Here we report the design, synthesis, and characterization of a new low-melt liquid copolymer based on poly(ε-caprolactone) (PCL) and establish its utility as a versatile delivery platform. Methods: The copolymer, mPA20, consisting of short PCL blocks connected via acid-labile acetal linkages, was synthesized using a one-pot reaction and its properties were comprehensively characterized. Results: mPA20 is an amorphous, injectable liquid at physiological temperature and can undergo pH-sensitive hydrolytic degradation. mPA20 bearing methacrylate end groups can be photo-crosslinked into solid matrices with tunable mechanical properties. A hydrophobic fluorophore, Nile Red (NR), was solubilized in mPA20 without any solvent. Sustained release of NR into aqueous medium was achieved using mPA20, either as an injectable liquid depot or a photo-crosslinked solid matrix. Further, mPA20 self-emulsified in water to form nanodroplets, which were subsequently photo-crosslinked into nanogels. Both the nanodroplets and nanogels mediated efficient intracellular delivery of NR with no cytotoxicity. Conclusions: mPA20, a new photo-crosslinkable, hydrophobic liquid copolymer with pH-sensitive degradability, is highly adaptable as either an injectable or implantable depot or nanoscale carrier for the controlled release and intracellular delivery of poorly soluble drugs. 

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating “avatars” (herein defined as an extension of “digital twins”) of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.