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Purpose: To explore the potential of growth hormone-releasing peptide 2 (GHRP-2) for tendon-bone healing in a rat rotator cuff tear (RCT) model.
Methods: The impact of GHRP-2 on M1 macrophage polarization in vitro was determined using real-time polymerase chain reaction, Western blot, and immunofluorescence staining. GHRP-2 was then applied in a rat RCT model, and the healing of the tendon-bone interface was systemically evaluated by histologic staining, radiologic assessments, gait analysis, and biomechanical tests. M1 macrophage polarization at the tendon-bone interface was assessed by immunofluorescence staining.
Results: GHRP-2 was found to reduce the expression of Cd86, Nos2, and tnfa (all P < .01), suggesting inhibited M1 macrophage polarization in vitro. The in vivo experiments showed that the proportion of M1 macrophages was reduced both 2 and 4 weeks after surgery (P < .01), and the number of M1 was reduced 4 weeks after surgery (P < .01) at the tendon-bone interface. The in vivo experiments also showed that histologic scores and bone mineral density were increased by GHRP-2 at 8 weeks postsurgery (P < .01), suggesting improved healing of the tendon-bone interface. Furthermore, the GHRP-2 group showed a better biomechanical property at both 4 and 8 weeks postsurgery, including maximal failure load, stiffness, and tension (all P < .01), and better gait parameters at 8 weeks postsurgery, including mean area of the left front foot and mean intensity of the right front foot (all P < .05).
Conclusions: GHRP-2 may be associated with decreased M1 macrophage production and increased histologic and biomechanical tendon-bone healing properties in a rat RCT model.
Clinical Relevance: The present study might be a transitional study to show the efficacy of GHRP-2 in enhancing bone-tendon healing and reduce retear rate after rotator cuff repair.
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http://dx.doi.org/10.1016/j.arthro.2024.11.094 | DOI Listing |
Front Bioeng Biotechnol
August 2025
Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, Guangzhou, Guangdong, China.
Introduction: During the healing process, the functional gradient attachment of the rotator cuff (RC) tendon-bone interface fails to regenerate, which severely impedes load transfer and stress dissipation, thereby increasing the risk of retears. As a result, the treatment of rotator cuff tears remains a significant clinical challenge.
Methods: In this study, a dual-crosslinked hyaluronic acid/polyethylene glycol (HA/PEG) hydrogel scaffold was synthesized using hyaluronic acid and polyethylene glycol as base materials.
ACS Nano
September 2025
Laboratory for Atomistic and Molecular Mechanics (LAMM), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Interfaces are everywhere in technology and engineering, from electronic circuit components to structural joints and biomedical implants. Understanding and controlling these interfaces is essential for advancing device efficiency, durability, and functionality. Nature has evolved intriguing strategies for joining soft and hard tissues through the enthesis, a specialized interface between tendon and bone that exhibits an unexpected compliant region critical for interface durability.
View Article and Find Full Text PDFStem Cell Res Ther
August 2025
Medical Research Center, Shandong Institute of Traumatic Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, China.
Background: The intact tendon-bone interface (TBI) consists of four histological layers-tendon, fibrocartilage, calcified fibrocartilage, and bone-that gradually merge into each other, making complete structural restoration after injury challenging. Osteoporosis poses a significant risk for rotator cuff tears (RCTs) and re-tears after arthroscopic rotator cuff repair (ARCR). Activating Leptin receptor (Lepr) mediated Stat3 signaling transduction facilitates the transcription of Runx2 and Sox9, respectively, and promotes osteogenesis and chondrogenesis.
View Article and Find Full Text PDFJ Shoulder Elbow Surg
August 2025
Department of Sports Medicine, Affiliated Hospital, Wuhan Sports University, Wuhan, 430079, China. Electronic address:
Background: Eccentric mechanical stimulation (EMS) has been proposed as a potential therapy for tendon-bone injuries. Macrophages, as key immune cells, may play a significant role in promoting tendon-bone injury healing through mechanical stimulation, due to their polarization. This study aims to investigate the role of macrophages in rotator cuff injury repair promoted by EMS.
View Article and Find Full Text PDFAm J Sports Med
September 2025
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background: The revision rate due to postoperative instability after anterior cruciate ligament reconstruction (ACLR) remains at 4% to 25%. The physiological mechanisms of tendon-bone healing involve intricate processes, particularly neovascularization and osseointegration at the bone tunnel interface. Currently, no standardized noninvasive method exists to comprehensively evaluate tendon-bone healing progression.
View Article and Find Full Text PDF