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Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis.

ABSTRACT: 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.

SUBMITTER: Kirsch JR

PROVIDER: S-EPMC9948766 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis.

Kirsch Jack R JR Williamson Amanda K AK Yeritsyan Diana D Blessing William A WA Momenzadeh Kaveh K Leach Todd R TR Williamson Patrick M PM Korunes-Miller Jenny T JT DeAngelis Joseph P JP Zurakowski David D Nazarian Rosalynn M RM Rodriguez Edward K EK Nazarian Ara A Grinstaff Mark W MW

Science translational medicine 20221012 666

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 treat ...[more]

PMID: 36223449

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Project description:Introduction:The standard open technique for carpal tunnel surgery has wound problems and complications significantly more than minimally invasive surgery using the Wongsiri technique with MiniSURE Kit® (Surgical Innovation Healthcare Co., Ltd, Bangkok, Thailand) and in particular, the open technique surgery requires a longer time for return to work. CTR surgery with endoscopic devices improves the results with fewer wound problems when compared with the commonly used open technique; however, nerve complications and injury are more prevalent with endoscopic surgery than with the open technique. The Wongsiri technique produces good results with new medical devices such as the MiniSURE View, for improved vision and line-of-sight, and the MiniSURE Cut for improved and complete cutting via the supraretinacular technique that may reduce the nerve problems associated with endoscopic tooling in the carpal tunnel. Purpose:To evaluate the results of the operation and postoperative outcomes of the Wongsiri technique with a MiniSURE Kit®. Methods:20 patients underwent carpal tunnel release using the Wongsiri technique and a MiniSURE Kit® with a five-step surgery: MIS starts when the surgeon makes a 1.5-1.8?cm incision, creates a working space, inserts the visual tube of MiniSURE View, inserts the freer, and then cuts the transverse carpal ligament by using the MiniSURE Cut. Results:All 20 successes of the Wongsiri technique and MiniSURE Kit® surgery occurred within 6.8 minutes operative time and a 12?mm wound size. A single outlier, in one case (6.7%), the patient experienced pillar pain which abated within one month. Patients can return to work in 7.3 days. Conclusions:The Wongsiri technique with the MiniSURE Kit® demonstrated good outcomes similar to the endoscope. By contrast with the endoscopic surgery, the Wongsiri technique with the MiniSURE Kit® reduced preop, operating, and postop time, many resources, and significant costs and resulted in no nerve problems or complications.

Dataset Information

Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis.

Publications

Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis.

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