No abstract

We report the synthesis of diblock poly-amido-saccharides (PASs) by sequential addition of variably protected glucose and galactose monomers via living anionic ring-opening polymerization. Diblock polymers with varied polymer length, hydrophobic to hydrophilic ratio, and stereochemistry of hydrophilic component were synthesized, characterized by NMR, IR, and GPC. These amphiphilic polymers self-assemble in water to form nanoparticles as determined by DLS, SEM, and cryo-TEM. Amphiphilic polymers with glucose-PAS hydrophobic and galactose-PAS hydrophilic blocks and degree of polymerization of 100 (100-EtGlc1-OHGal3diblock PAS) form spherical nanostructures and are non-cytotoxic.

Diagnostic testing that facilitates containment, surveillance, and treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), or future respiratory viruses, depends on a sample collection device that efficiently collects nasopharyngeal tissue and that can be manufactured on site when an outbreak or public health emergency is declared by a government. Here two novel stereolithography‐based three‐dimensional (3D)‐printed nasopharyngeal swabs are reported which are made using a biocompatible and sterilizable photoresist. Such swabs are readily manufactured on‐site and on‐demand to ensure availability, if supply chain shortages emerge. Additionally, the 3D‐printed swabs easily adapt to current workflow and testing procedures in hospital clinical laboratories to allow for effortless scaling up of test kits. Finally, the 3D‐printed nasopharyngeal swabs demonstrate concordant SARS‐CoV‐2 testing results between the 3D‐printed swabs and the COPAN commercial swabs, and enable detection of SARS‐CoV‐2 in clinical samples obtained from autopsies.

Sensor-integrated wound dressings are emerging tools applicable to a wide variety of medical applications from emergency triage to at-home monitoring. Uncomfortable, unnecessary wound dressing changes may be avoided by providing quantitative insight into tissue characteristics related to wound healing such as tissue oxygenation, pH, and exudate/transudate volume. Here, a simple cost-effective methodology for quantifying oxygen and pH in a swellable hydrogel dressing using a single photograph is presented. The red and green luminescence of a novel dendritic polyamine Pt-porphyrin and fluorescein conjugate quantitatively responds to oxygen and pH, respectively, and enables robust sensing. The porphyrin conjugate, when combined with a four-arm star polyethylene glycol (PEG) amine polymer, rapidly crosslinks at room temperature with an N-hydroxysuccinimide (NHS)-PEG crosslinker to form a color-changing hydrogel dressing with tunable swelling capabilities applicable to a variety of wound environments. An inexpensive digital single-lens reflex (DSLR) camera modified with bandpass filters captures the hydrogel luminescence using simple macroscopic photography, and conversion to HSB colorspace allows for intensity-independent image analysis of the hydrogels' dual modality response. The hydrogel formulation exhibits a robust and validated visible red-orange-green "traffic light" spectrum in response to oxygen changes, regardless of swelling state, pH, or autofluorescence from skin, thereby enabling the clinician friendly naked-eye feedback.

Substantial advances in biotherapeutics are distinctly lacking for musculoskeletal diseases. Musculoskeletal diseases are biomechanically complex and localized, highlighting the need for novel therapies capable of addressing these issues. All frontline treatment options for arthrofibrosis, a debilitating musculoskeletal disease, fail to treat the disease etiology—the accumulation of fibrotic tissue within the joint space. For millions of patients each year, the lack of modern and effective treatment options necessitates surgery in an attempt to regain joint range of motion (ROM) and escape prolonged pain. Human relaxin-2 (RLX), an endogenous peptide hormone with antifibrotic and antifibrogenic activity, is a promising biotherapeutic candidate for musculoskeletal fibrosis. However, RLX has previously faltered through multiple clinical programs because of pharmacokinetic barriers. Here, we describe the design and in vitro characterization of a tailored drug delivery system for the sustained release of RLX. Drug-loaded, polymeric microparticles released RLX over a multiweek time frame without altering peptide structure or bioactivity. In vivo, intraarticular administration of microparticles in rats resulted in prolonged, localized concentrations of RLX with reduced systemic drug exposure. Furthermore, a single injection of RLX-loaded microparticles restored joint ROM and architecture in an atraumatic rat model of arthrofibrosis with clinically derived end points. Finally, confirmation of RLX receptor expression, RXFP1, in multiple human tissues relevant to arthrofibrosis suggests the clinical translational potential of RLX when administered in a sustained and targeted manner.