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Bone injuries such as fractures are one major cause of morbidities worldwide. A considerable number of fractures suffer from delayed healing, and the unresolved acute pain may transition to chronic and maladaptive pain. Current management of pain involves treatment with NSAIDs and opioids with substantial adverse effects. Herein, we tested the hypothesis that the purine molecule, adenosine, can simultaneously alleviate pain and promote healing in a mouse model of tibial fracture by targeting distinctive adenosine receptor subtypes in different cell populations. To achieve this, a biomaterial‐assisted delivery of adenosine is utilized to localize and prolong its therapeutic effect at the injury site. The results demonstrate that local delivery of adenosine inhibited the nociceptive activity of peripheral neurons through activation of adenosine A1 receptor (ADORA1) and mitigated pain as demonstrated by weight bearing and open field movement tests. Concurrently, local delivery of adenosine at the fracture site promoted osteogenic differentiation of mesenchymal stromal cells through adenosine A2B receptor (ADORA2B) resulting in improved bone healing as shown by histological analyses and microCT imaging. This study demonstrates the dual role of adenosine and its material‐assisted local delivery as a feasible therapeutic approach to treat bone trauma and associated pain. [ABSTRACT FROM AUTHOR]

More than 80% of the bacterial infections are associated with biofilm formation. To combat infections, amphiphilic small molecules have been developed as promising antibiofilm agents. However, cytotoxicity of such molecules still remains a major problem. Herein we demonstrate a concept in which antibacterial versus cytotoxic activities of cationic small molecules are tuned by spatial positioning of hydrophobic moieties while keeping positive charges constant. Compared to the molecules with more pendent hydrophobicity from positive centers (MIC = 1-4 μg/mL and HC50 = 60-65 μg/mL), molecules with more confined hydrophobicity between two centers show similar antibacterial activity but significantly less toxicity toward human erythrocytes (MIC = 1-4 μg/mL and HC50 = 805-1242 μg/mL). Notably, the optimized molecule is shown to be nontoxic toward human cells (HEK 293) at a concentration at which it eradicates established bacterial biofilms. The molecule is also shown to eradicate preformed bacterial biofilm in vivo in a murine model of superficial skin infection. [ABSTRACT FROM AUTHOR]

Rationally designed amphiphilic small molecules selectively kill drug-sensitive and drug-resistant bacteria over mammalian cells. The small molecules disperse preformed biofilms and reduce viable bacterial count in the biofilms. Moreover, this class of membrane-active molecules disarms the development of bacterial resistance. [ABSTRACT FROM AUTHOR]

Correction for ‘Selective and broad spectrum amphiphilic small molecules to combat bacterial resistance and eradicate biofilms’ by Jiaul Hoque et al., Chem. Commun., 2015, 51, 13670–13673. [ABSTRACT FROM AUTHOR]