Molecular mechanism of magnesium alloy promoting macrophage M2 polarization through modulation of PI3K/AKT signaling pathway for tendon-bone healing in rotator cuff injury repair.
10.7507/1002-1892.202410010
- Author:
Xianhao SHENG
1
;
Wen ZHANG
2
;
Shoulong SONG
1
;
Fei ZHANG
1
;
Baoxiang ZHANG
2
;
Xiaoying TIAN
2
;
Wentao XIONG
1
;
Yingguang ZHU
1
;
Yuxin XIE
1
;
Zi'ang LI
1
;
Lili TAN
2
;
Qiang ZHANG
3
;
Yan WANG
3
Author Information
1. Chinese PLA Medical School, Beijing, 100853, P. R. China.
2. Institute of Metal Research, Chinese Academy of Sciences, Shenyang Liaoning, 110013, P. R. China.
3. Department of Orthopedics, the Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100048, P. R. China.
- Publication Type:Journal Article
- Keywords:
Magnesium alloy;
macrophage;
phosphatidylinositol 3 kinase;
protein kinase B;
rotator cuff tear;
signaling pathway;
tendon-bone healing
- MeSH:
Animals;
Rotator Cuff Injuries/metabolism*;
Rats, Sprague-Dawley;
Signal Transduction;
Wound Healing/drug effects*;
Alloys/pharmacology*;
Rats;
Proto-Oncogene Proteins c-akt/metabolism*;
Rotator Cuff/metabolism*;
Macrophages/metabolism*;
Magnesium/pharmacology*;
Phosphatidylinositol 3-Kinases/metabolism*;
Vascular Endothelial Growth Factor A/metabolism*;
Male;
Biocompatible Materials;
Bone Morphogenetic Protein 2/metabolism*
- From:
Chinese Journal of Reparative and Reconstructive Surgery
2025;39(2):174-186
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To evaluate the effect of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms.
METHODS:Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expressions of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expressions of Arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR.
RESULTS:Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis results revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate load in group A was consistently higher than in group B, and the stiffness of group A was also greater than that of group B at 4 weeks, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expressions of VEGF and BMP-2 were significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway.
CONCLUSION:Biodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.
