{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:37:55Z","timestamp":1790321875713,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T00:00:00Z","timestamp":1511308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Designing drugs to treat diseases associated with articular joints, particularly those targeting chondrocytes, is challenging due to unique local environmental constraints including the avascular nature of cartilage, the absence of a closed joint compartment, and a highly cross\u2010linked extracellular matrix. In an effort to address these challenges, we developed a novel strategy to prolong residence time of intra\u2010articularly administered protein therapeutics. Avimer domains are naturally found in membrane polypeptides and mediate diverse protein\u2013protein interactions. Screening of a phage Avimer domain library led to identification of several low affinity type II collagen\u2010binding Avimers. Following several rounds of mutagenesis and reselection, these initial hits were transformed to high affinity, selective type II collagen\u2010binding Avimers. One such Avimer (M26) persisted in rat knees for at least 1 month following intra\u2010articular administration. Fusion of this Avimer to a candidate therapeutic payload, IL\u20101Ra, yielded a protein construct which simultaneously bound to type II collagen and to IL\u20101 receptor. In vitro, IL\u20101Ra_M26 bound selectively to cartilage explants and remained associated even after extensive washing. Binding appeared to occur preferentially to pericellular regions surrounding chondrocytes. An acute intra\u2010articular IL\u20101\u2010induced IL\u20106 challenge rat model was employed to assess in vivo pharmacodynamics. Whereas both IL\u20101Ra_M26 and native IL\u20101Ra inhibited IL\u20106 output when co\u2010administered with the IL\u20101 challenge, only IL\u20101Ra_M26 inhibited when administered 1 week prior to IL\u20101 challenge. Collagen\u2010binding Avimers thus represent a promising strategy for enhancing cartilage residence time of protein therapeutics. \u00a9 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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