Research progress on the regulation of macrophage polarization by mechanical stimulation in wound healing_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

XU Chenlu ^1,2 , YU Dan ¹ ,  ZHU Huiyong ¹

1. Department of Stomatology, the First Affiliated Hospital of Medical College of Zhejiang University, Hangzhou Zhejiang, 310003, P. R. China;
2. Medical College of Zhejiang University, Hangzhou Zhejiang, 310030, P. R. China;

Corresponding author：

ZHU Huiyong, Email: zhuhuiyong@zju.edu.cn

Keywords：

Macrophages; polarization; mechanical stimulation; wound healing; tissue engineering

DOI：

10.7507/1002-1892.202201028

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summary the regulatory effect of mechanical stimulation on macrophage polarization in wound healing, and explore the application prospect of mechanical stimulation in tissue engineering. Methods The related domestic and foreign literature in recent years was extensive reviewed, and the different phenotypes of macrophages and their roles in wound healing, the effect of mechanical stimulation on macrophage polarization and its application in tissue engineering were analyzed. Results Macrophages have functional diversity, with two phenotypes: pro-inflammatory (M1 type) and anti-inflammatory (M2 type), and the cells exhibit different activation phenotypes and play corresponding functions under different stimuli. The mechanical force of different types, sizes, and amplitudes can directly or indirectly guide macrophages to transform into different phenotypes, and then affect tissue repair. This feature can be used in tissue engineering to selectively regulate macrophage polarization. Conclusion Mechanical stimulation plays an vital role in regulating macrophage polarization, but its specific role and mechanism remain ambiguous and need to be further explored.

Citation： XU Chenlu, YU Dan, ZHU Huiyong. Research progress on the regulation of macrophage polarization by mechanical stimulation in wound healing. Chinese Journal of Reparative and Reconstructive Surgery, 2022, 36(8): 1041-1046. doi: 10.7507/1002-1892.202201028 Copy

1.	Blériot C, Chakarov S, Ginhoux F. Determinants of resident tissue macrophage identity and function. Immunity, 2020, 52(6): 957-970.
2.	Chu SY, Chou CH, Huang HD, et al. Mechanical stretch induces hair regeneration through the alternative activation of macrophages. Nat Commun, 2019, 10(1): 1524. doi: 10.1038/s41467-019-09402-8.
3.	Mojena-Medina D, Martínez-Hernández M, de la Fuente M, et al. Design, implementation, and validation of a piezoelectric device to study the effects of dynamic mechanical stimulation on cell proliferation, migration and morphology. Sensors (Basel), 2020, 20(7): 2155. doi: 10.3390/s20072155.
4.	Wang Y, Fan Y, Liu H. Macrophage polarization in response to biomaterials for vascularization. Ann Biomed Eng, 2021, 49(9): 1992-2005.
5.	林雁鸿, 周清清, 李春霖, 等. 创伤修复机制和治疗进展. 中国现代药物应用, 2019, 13(23): 230-232.
6.	姜琦, 李京蔓, 侯亚义. 巨噬细胞参与伤口愈合和组织再生的研究进展. 中国免疫学杂志, 2020, 36(6): 759-766.
7.	秦烨, 张国权, 李覃, 等. 巨噬细胞表型极化及其对生物材料植入的影响. 生物医学工程与临床, 2020, 24(2): 228-232.
8.	Xu X, Gu S, Huang X, et al. The role of macrophages in the formation of hypertrophic scars and keloids. Burns Trauma, 2020, 8: tkaa006. doi: 10.1093/burnst/tkaa006.
9.	Wang LX, Zhang SX, Wu HJ, et al. M2b macrophage polarization and its roles in diseases. J Leukoc Biol, 2019, 106(2): 345-358.
10.	Davis MJ, Tsang TM, Qiu Y, et al. Macrophage M1/M2 polarization dynamically adapts to changes in cytokine microenvironments in cryptococcus neoformans infection. mBio, 2013, 4(3): e00264-213. doi: 10.1128/mBio.00264-13.
11.	Savitri C, Ha SS, Liao E, et al. Extracellular matrices derived from different cell sources and their effect on macrophage behavior and wound healing. J Mater Chem B, 2020, 8(42): 9744-9755.
12.	Aitcheson SM, Frentiu FD, Hurn SE, et al. Skin wound healing: normal macrophage function and macrophage dysfunction in diabetic wounds. Molecules, 2021, 26(16): 4917. doi: 10.3390/molecules26164917.
13.	Kim SY, Nair MG. Macrophages in wound healing: activation and plasticity. Immunol Cell Biol, 2019, 97(3): 258-267.
14.	Louiselle AE, Niemiec SM, Zgheib C, et al. Macrophage polarization and diabetic wound healing. Transl Res, 2021, 236: 109-116.
15.	Wu J, Zhang L, Shi J, et al. Macrophage phenotypic switch orchestrates the inflammation and repair/regeneration following acute pancreatitis injury. EBioMedicine, 2020, 58: 102920. doi: 10.1016/j.ebiom.2020.102920.
16.	张慜晨, 高伟成. 创面愈合过程中巨噬细胞调控机制的研究进展. 组织工程与重建外科杂志, 2019, 15(3): 204-207.
17.	Chen L, Wang J, Li S, et al. The clinical dynamic changes of macrophage phenotype and function in different stages of human wound healing and hypertrophic scar formation. Int Wound J, 2019, 16(2): 360-369.
18.	Villarreal-Leal RA, Healey GD, Corradetti B. Biomimetic immunomodulation strategies for effective tissue repair and restoration. Adv Drug Deliv Rev, 2021, 179: 113913. doi: 10.1016/j.addr.2021.113913.
19.	Antmen E, Vrana NE, Hasirci V. The role of biomaterials and scaffolds in immune responses in regenerative medicine: macrophage phenotype modulation by biomaterial properties and scaffold architectures. Biomater Sci, 2021, 9(24): 8090-8110.
20.	Barthes J, Lagarrigue P, Riabov V, et al. Biofunctionalization of 3D-printed silicone implants with immunomodulatory hydrogels for controlling the innate immune response: An in vivo model of tracheal defect repair. Biomaterials, 2021, 268: 120549. doi: 10.1016/j.biomaterials.2020.120549.
21.	Novikova OA, Laktionov PP, Karpenko AA. The roles of mechanotransduction, vascular wall cells, and blood cells in atheroma induction. Vascular, 2019, 27(1): 98-109.
22.	Wolf MP, Hunziker P. Atherosclerosis: insights into vascular pathobiology and outlook to novel treatments. J Cardiovasc Transl Res, 2020, 13(5): 744-757.
23.	Adams S, Wuescher LM, Worth R, et al. Mechano-immunomodulation: mechanoresponsive changes in macrophage activity and polarization. Ann Biomed Eng, 2019, 47(11): 2213-2231.
24.	陈成, 张晓容, 胡晓红, 等. 单核-巨噬细胞的异质性及其对创面愈合的调控研究进展. 免疫学杂志, 2021, 37(2): 172-178.
25.	Barnes LA, Marshall CD, Leavitt T, et al. Mechanical forces in cutaneous wound healing: emerging therapies to minimize scar formation. Adv Wound Care (New Rochelle), 2018, 7(2): 47-56.
26.	Le Roux AL, Quiroga X, Walani N, et al. The plasma membrane as a mechanochemical transducer. Philos Trans R Soc Lond B Biol Sci, 2019, 374(1779): 20180221. doi: 10.1098/rstb.2018.0221.
27.	Ku DN, Giddens DP, Zarins CK, et al. Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis, 1985, 5(3): 293-302.
28.	Stone PH, Coskun AU, Kinlay S, et al. Effect of endothelial shear stress on the progression of coronary artery disease, vascular remodeling, and in-stent restenosis in humans: in vivo 6-month follow-up study. Circulation, 2003, 108(4): 438-444.
29.	Fahy N, Menzel U, Alini M, et al. Shear and dynamic compression modulates the inflammatory phenotype of human monocytes in vitro. Front Immunol, 2019, 10: 383. doi: 10.3389/fimmu.2019.00383.
30.	Wissing TB, van Haaften EE, Koch SE, et al. Hemodynamic loads distinctively impact the secretory profile of biomaterial-activated macrophages-implications for in situ vascular tissue engineering. Biomater Sci, 2019, 8(1): 132-147.
31.	Ferrier GM, McEvoy A, Evans CE, et al. The effect of cyclic pressure on human monocyte-derived macrophages in vitro. J Bone Joint Surg (Br), 2000, 82(5): 755-759.
32.	Evans CE, Mylchreest S, Andrew JG. Age of donor alters the effect of cyclic hydrostatic pressure on production by human macrophages and osteoblasts of sRANKL, OPG and RANK. BMC Musculoskelet Disord, 2006, 7: 21. doi: 10.1186/1471-2474-7-21.
33.	Zhang R, Wan J, Wang H. Mechanical strain triggers differentiation of dental mesenchymal stem cells by activating osteogenesis-specific biomarkers expression. Am J Transl Res, 2019, 11(1): 233-244.
34.	Dong L, Song Y, Zhang Y, et al. Mechanical stretch induces osteogenesis through the alternative activation of macrophages. J Cell Physiol, 2021, 236(9): 6376-6390.
35.	陈咪咪, 褚耿磊, 黄迎康, 等. 力学拉伸对巨噬细胞极化影响的研究. 中国免疫学杂志, 2018, 34(12): 1788-1793.
36.	Liang W, Ding P, Qian J, et al. Polarized M2 macrophages induced by mechanical stretching modulate bone regeneration of the craniofacial suture for midfacial hypoplasia treatment. Cell Tissue Res, 2021, 386(3): 585-603.
37.	Dziki JL, Giglio RM, Sicari BM, et al. The effect of mechanical loading upon extracellular matrix bioscaffold-mediated skeletal muscle remodeling. Tissue Eng Part A, 2018, 24(1-2): 34-46.
38.	Schoenenberger AD, Tempfer H, Lehner C, et al. Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo. Biomaterials, 2020, 249: 120034. doi: 10.1016/j.biomaterials.2020.120034.
39.	Battiston KG, Labow RS, Simmons CA, et al. Immunomodulatory polymeric scaffold enhances extracellular matrix production in cell co-cultures under dynamic mechanical stimulation. Acta Biomater, 2015, 24: 74-86.
40.	Chen R, Hao Z, Wang Y, et al. Mesenchymal stem cell-immune cell interaction and related modulations for bone tissue engineering. Stem Cells Int, 2022, 2022: 7153584. doi: 10.1155/2022/7153584.
41.	Ylöstalo JH, Bartosh TJ, Coble K, et al. Human mesenchymal stem/stromal cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype. Stem Cells, 2012, 30(10): 2283-2296.
42.	Ueno M, Lo CW, Barati D, et al. Interleukin-4 overexpressing mesenchymal stem cells within gelatin-based microribbon hydrogels enhance bone healing in a murine long bone critical-size defect model. J Biomed Mater Res A, 2020, 108(11): 2240-2250.
43.	Xia Y, Rao L, Yao H, et al. Engineering macrophages for cancer immunotherapy and drug delivery. Adv Mater, 2020, 32(40): e2002054. doi: 10.1002/adma.202002054.
44.	Dervan A, Franchi A, Almeida-Gonzalez FR, et al. Biomaterial and therapeutic approaches for the manipulation of macrophage phenotype in peripheral and central nerve repair. Pharmaceutics, 2021, 13(12): 2161. doi: 10.3390/pharmaceutics13122161.
45.	Martin KE, García AJ. Macrophage phenotypes in tissue repair and the foreign body response: Implications for biomaterial-based regenerative medicine strategies. Acta Biomater, 2021, 133: 4-16.

1. Blériot C, Chakarov S, Ginhoux F. Determinants of resident tissue macrophage identity and function. Immunity, 2020, 52(6): 957-970.
2. Chu SY, Chou CH, Huang HD, et al. Mechanical stretch induces hair regeneration through the alternative activation of macrophages. Nat Commun, 2019, 10(1): 1524. doi: 10.1038/s41467-019-09402-8.
3. Mojena-Medina D, Martínez-Hernández M, de la Fuente M, et al. Design, implementation, and validation of a piezoelectric device to study the effects of dynamic mechanical stimulation on cell proliferation, migration and morphology. Sensors (Basel), 2020, 20(7): 2155. doi: 10.3390/s20072155.
4. Wang Y, Fan Y, Liu H. Macrophage polarization in response to biomaterials for vascularization. Ann Biomed Eng, 2021, 49(9): 1992-2005.
5. 林雁鸿, 周清清, 李春霖, 等. 创伤修复机制和治疗进展. 中国现代药物应用, 2019, 13(23): 230-232.
6. 姜琦, 李京蔓, 侯亚义. 巨噬细胞参与伤口愈合和组织再生的研究进展. 中国免疫学杂志, 2020, 36(6): 759-766.
7. 秦烨, 张国权, 李覃, 等. 巨噬细胞表型极化及其对生物材料植入的影响. 生物医学工程与临床, 2020, 24(2): 228-232.
8. Xu X, Gu S, Huang X, et al. The role of macrophages in the formation of hypertrophic scars and keloids. Burns Trauma, 2020, 8: tkaa006. doi: 10.1093/burnst/tkaa006.
9. Wang LX, Zhang SX, Wu HJ, et al. M2b macrophage polarization and its roles in diseases. J Leukoc Biol, 2019, 106(2): 345-358.
10. Davis MJ, Tsang TM, Qiu Y, et al. Macrophage M1/M2 polarization dynamically adapts to changes in cytokine microenvironments in cryptococcus neoformans infection. mBio, 2013, 4(3): e00264-213. doi: 10.1128/mBio.00264-13.
11. Savitri C, Ha SS, Liao E, et al. Extracellular matrices derived from different cell sources and their effect on macrophage behavior and wound healing. J Mater Chem B, 2020, 8(42): 9744-9755.
12. Aitcheson SM, Frentiu FD, Hurn SE, et al. Skin wound healing: normal macrophage function and macrophage dysfunction in diabetic wounds. Molecules, 2021, 26(16): 4917. doi: 10.3390/molecules26164917.
13. Kim SY, Nair MG. Macrophages in wound healing: activation and plasticity. Immunol Cell Biol, 2019, 97(3): 258-267.
14. Louiselle AE, Niemiec SM, Zgheib C, et al. Macrophage polarization and diabetic wound healing. Transl Res, 2021, 236: 109-116.
15. Wu J, Zhang L, Shi J, et al. Macrophage phenotypic switch orchestrates the inflammation and repair/regeneration following acute pancreatitis injury. EBioMedicine, 2020, 58: 102920. doi: 10.1016/j.ebiom.2020.102920.
16. 张慜晨, 高伟成. 创面愈合过程中巨噬细胞调控机制的研究进展. 组织工程与重建外科杂志, 2019, 15(3): 204-207.
17. Chen L, Wang J, Li S, et al. The clinical dynamic changes of macrophage phenotype and function in different stages of human wound healing and hypertrophic scar formation. Int Wound J, 2019, 16(2): 360-369.
18. Villarreal-Leal RA, Healey GD, Corradetti B. Biomimetic immunomodulation strategies for effective tissue repair and restoration. Adv Drug Deliv Rev, 2021, 179: 113913. doi: 10.1016/j.addr.2021.113913.
19. Antmen E, Vrana NE, Hasirci V. The role of biomaterials and scaffolds in immune responses in regenerative medicine: macrophage phenotype modulation by biomaterial properties and scaffold architectures. Biomater Sci, 2021, 9(24): 8090-8110.
20. Barthes J, Lagarrigue P, Riabov V, et al. Biofunctionalization of 3D-printed silicone implants with immunomodulatory hydrogels for controlling the innate immune response: An in vivo model of tracheal defect repair. Biomaterials, 2021, 268: 120549. doi: 10.1016/j.biomaterials.2020.120549.
21. Novikova OA, Laktionov PP, Karpenko AA. The roles of mechanotransduction, vascular wall cells, and blood cells in atheroma induction. Vascular, 2019, 27(1): 98-109.
22. Wolf MP, Hunziker P. Atherosclerosis: insights into vascular pathobiology and outlook to novel treatments. J Cardiovasc Transl Res, 2020, 13(5): 744-757.
23. Adams S, Wuescher LM, Worth R, et al. Mechano-immunomodulation: mechanoresponsive changes in macrophage activity and polarization. Ann Biomed Eng, 2019, 47(11): 2213-2231.
24. 陈成, 张晓容, 胡晓红, 等. 单核-巨噬细胞的异质性及其对创面愈合的调控研究进展. 免疫学杂志, 2021, 37(2): 172-178.
25. Barnes LA, Marshall CD, Leavitt T, et al. Mechanical forces in cutaneous wound healing: emerging therapies to minimize scar formation. Adv Wound Care (New Rochelle), 2018, 7(2): 47-56.
26. Le Roux AL, Quiroga X, Walani N, et al. The plasma membrane as a mechanochemical transducer. Philos Trans R Soc Lond B Biol Sci, 2019, 374(1779): 20180221. doi: 10.1098/rstb.2018.0221.
27. Ku DN, Giddens DP, Zarins CK, et al. Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis, 1985, 5(3): 293-302.
28. Stone PH, Coskun AU, Kinlay S, et al. Effect of endothelial shear stress on the progression of coronary artery disease, vascular remodeling, and in-stent restenosis in humans: in vivo 6-month follow-up study. Circulation, 2003, 108(4): 438-444.
29. Fahy N, Menzel U, Alini M, et al. Shear and dynamic compression modulates the inflammatory phenotype of human monocytes in vitro. Front Immunol, 2019, 10: 383. doi: 10.3389/fimmu.2019.00383.
30. Wissing TB, van Haaften EE, Koch SE, et al. Hemodynamic loads distinctively impact the secretory profile of biomaterial-activated macrophages-implications for in situ vascular tissue engineering. Biomater Sci, 2019, 8(1): 132-147.
31. Ferrier GM, McEvoy A, Evans CE, et al. The effect of cyclic pressure on human monocyte-derived macrophages in vitro. J Bone Joint Surg (Br), 2000, 82(5): 755-759.
32. Evans CE, Mylchreest S, Andrew JG. Age of donor alters the effect of cyclic hydrostatic pressure on production by human macrophages and osteoblasts of sRANKL, OPG and RANK. BMC Musculoskelet Disord, 2006, 7: 21. doi: 10.1186/1471-2474-7-21.
33. Zhang R, Wan J, Wang H. Mechanical strain triggers differentiation of dental mesenchymal stem cells by activating osteogenesis-specific biomarkers expression. Am J Transl Res, 2019, 11(1): 233-244.
34. Dong L, Song Y, Zhang Y, et al. Mechanical stretch induces osteogenesis through the alternative activation of macrophages. J Cell Physiol, 2021, 236(9): 6376-6390.
35. 陈咪咪, 褚耿磊, 黄迎康, 等. 力学拉伸对巨噬细胞极化影响的研究. 中国免疫学杂志, 2018, 34(12): 1788-1793.
36. Liang W, Ding P, Qian J, et al. Polarized M2 macrophages induced by mechanical stretching modulate bone regeneration of the craniofacial suture for midfacial hypoplasia treatment. Cell Tissue Res, 2021, 386(3): 585-603.
37. Dziki JL, Giglio RM, Sicari BM, et al. The effect of mechanical loading upon extracellular matrix bioscaffold-mediated skeletal muscle remodeling. Tissue Eng Part A, 2018, 24(1-2): 34-46.
38. Schoenenberger AD, Tempfer H, Lehner C, et al. Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo. Biomaterials, 2020, 249: 120034. doi: 10.1016/j.biomaterials.2020.120034.
39. Battiston KG, Labow RS, Simmons CA, et al. Immunomodulatory polymeric scaffold enhances extracellular matrix production in cell co-cultures under dynamic mechanical stimulation. Acta Biomater, 2015, 24: 74-86.
40. Chen R, Hao Z, Wang Y, et al. Mesenchymal stem cell-immune cell interaction and related modulations for bone tissue engineering. Stem Cells Int, 2022, 2022: 7153584. doi: 10.1155/2022/7153584.
41. Ylöstalo JH, Bartosh TJ, Coble K, et al. Human mesenchymal stem/stromal cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype. Stem Cells, 2012, 30(10): 2283-2296.
42. Ueno M, Lo CW, Barati D, et al. Interleukin-4 overexpressing mesenchymal stem cells within gelatin-based microribbon hydrogels enhance bone healing in a murine long bone critical-size defect model. J Biomed Mater Res A, 2020, 108(11): 2240-2250.
43. Xia Y, Rao L, Yao H, et al. Engineering macrophages for cancer immunotherapy and drug delivery. Adv Mater, 2020, 32(40): e2002054. doi: 10.1002/adma.202002054.
44. Dervan A, Franchi A, Almeida-Gonzalez FR, et al. Biomaterial and therapeutic approaches for the manipulation of macrophage phenotype in peripheral and central nerve repair. Pharmaceutics, 2021, 13(12): 2161. doi: 10.3390/pharmaceutics13122161.
45. Martin KE, García AJ. Macrophage phenotypes in tissue repair and the foreign body response: Implications for biomaterial-based regenerative medicine strategies. Acta Biomater, 2021, 133: 4-16.

Chinese Journal of Reparative and Reconstructive Surgery

Research progress on the regulation of macrophage polarization by mechanical stimulation in wound healing

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