Cartilage defects are one of the most common symptoms of osteoarthritis (OA), a degenerative disease that affects millions of people world-wide and places a significant socio-economic burden on society. Hydrogels, which are a class of biomaterials that are elastic, and display smooth surfaces while exhibiting high water content, are promising candidates for cartilage regeneration. In recent years, various kinds of hydrogels have been developed and applied for the repair of cartilage defects in vitro or in vivo, some of which are hopeful to enter clinical trials. In this review, recent research findings and developments of hydrogels for cartilage defects repair are summarized. We discuss the principle of cartilage regeneration, and outline the requirements that have to be fulfilled for the deployment of hydrogels for medical applications. We also highlight the development of advanced hydrogels with tailored properties for different kinds of cartilage defects to meet the requirements of cartilage tissue engineering and precision medicine.

Delivery of therapeutic compounds to the site of action is crucial. While many chemical substances such as beta-lactam antibiotics can reach therapeutic levels in most parts throughout the human body after administration, substances of higher molecular weight such as therapeutic proteins may not be able to reach the site of action (e.g., an infection) and are therefore ineffective.

Pulmonary diseases of viral origin are often followed by the manifestation of secondary infections, leading to further clinical complications and negative disease outcomes. Thus, research on secondary infections is essential. Here, we review clinical data of secondary bacterial infections developed after the onset of pulmonary viral infections. We review the most recent clinical data and current knowledge of secondary bacterial infections and their treatment in SARS-CoV-2 positive patients; case reports from SARS-CoV, MERS-CoV, SARS-CoV2 and the best-studied respiratory virus, influenza, are described. We outline treatments used or prophylactic measures employed for secondary bacterial infections. This evaluation includes recent clinical reports of pulmonary viral infections, including those by COVID-19, that reference secondary infections. Where data was provided for COVID-19 patients, a mortality rate of 15.2% due to secondary bacterial infections was observed for patients with pneumonia (41 of 268). Most clinicians treated patients with SARS-CoV-2 infections with prophylactic antibiotics (63.7%, n = 1,901), compared to 73.5% (n = 3,072) in all clinical reports of viral pneumonia included in this review. For all cases of viral pneumonia, a mortality rate of 10.9% due to secondary infections was observed (53 of 482). Most commonly, quinolones, cephalosporins and macrolides were administered, but also the glycopeptide vancomycin. Several bacterial pathogens appear to be prevalent as causative agents of secondary infections, including antibiotic-resistant strains of Staphylococcus aureus and Klebsiella pneumoniae.

Multidrug-resistant bacterial infections are becoming increasingly common, with only few last-resort antibiotics such as colistin available for clinical therapy. An alternative therapeutic strategy gaining momentum is phage therapy, which has the advantage of not being affected by bacterial resistance to antibiotics. However, a major challenge in phage therapy is the rapid emergence of phage-resistant bacteria. In this work, our main aim was to understand the mechanisms of phage-resistance used by the top priority pathogen Acinetobacter baumannii. We isolated the novel phage Phab24, capable of infecting colistin-sensitive and -resistant strains of A. baumannii. After co-incubating Phab24 with its hosts, we obtained phage-resistant mutants which were characterized on both genotypic and phenotypic levels. Using whole genome sequencing, we identified phage-resistant strains that displayed mutations in genes that alter the architecture of the bacterial envelope at two levels: the capsule and the outer membrane. Using an adsorption assay, we confirmed that phage Phab24 uses the bacterial capsule as its primary receptor, with the outer membrane possibly serving as the secondary receptor. Interestingly, the phage-resistant isolates were less virulent compared to the parental strains in a Galleria mellonella infection model. Most importantly, we observed that phage-resistant bacteria that evolved in the absence of antibiotics exhibited an increased sensitivity to colistin, even though the antibiotic resistance mechanism per se remained unaltered. This increase in antibiotic sensitivity is a direct consequence of the phage-resistance mechanism, and could potentially be exploited in the clinical setting.