Research progress on extracellular vesicles derived from platelet-rich plasma in tissue injury repair and regeneration_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

HAN Jiaxuan ^1,2 ,  CHENG Biao ^1,2

1. Guangdong Pharmaceutical University, Guangzhou Guangdong, 510006, P. R. China;
2. Department of Burns and Plastic Surgery, General Hospital of Southern Theater Command of Chinese PLA, Guangzhou Guangdong, 510010, P. R. China;

Corresponding?author：

CHENG Biao, Email: chengbiaocheng@163.com

Keywords：

Platelet-rich plasma; extracellular vesicles; tissue repair; regenerative medicine; cell-free therapy

DOI：

10.7507/1002-1892.202511101

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To delineate the mechanistic role of platelet-rich plasma (PRP)-derived extracellular vesicles (EVs) in tissue repair and regeneration, and evaluate their clinical translation potential. Methods A systematic evidence synthesis was conducted through critical analysis of contemporary domestic and international literature, focusing on PRP-EVs’ biophysical properties, signal transduction networks, and multi-tissue regenerative efficacy. Results PRP-EVs coordinate hemostasis, anti-inflammatory modulation, angiogenesis, and tissue plasticity through mediation of cellular proliferation, migration, and differentiation. Their low immunogenicity and biostability constitute a novel cell-free therapeutic paradigm. Conclusion PRP-EVs exhibit substantial translational merit in regenerative medicine, yet persistent impediments in standardized isolation protocols, longitudinal biosafety verification, and clinical translation frameworks necessitate resolution.

1.	Kim HY, Kwon S, Um W, et al. Functional extracellular vesicles for regenerative medicine. Small, 2022, 18(36): e2106569. doi: 10.1002/smll.202106569.
2.	Katz JN. Platelet-rich plasma for osteoarthritis and achilles tendinitis. JAMA, 2021, 326(20): 2012-2014.
3.	Anitua E, Fernández-de-Retana S, Alkhraisat MH. Platelet rich plasma in oral and maxillofacial surgery from the perspective of composition. Platelets, 2021, 32(2): 174-182.
4.	Gentile P, Calabrese C, De Angelis B, et al. Impact of the different preparation methods to obtain autologous non-activated platelet-rich plasma (A-PRP) and activated platelet-rich plasma (AA-PRP) in plastic surgery: Wound healing and hair regrowth evaluation. Int J Mol Sci, 2020, 21(2): 431. doi: 10.3390/ijms21020431.
5.	Alam M, Hughart R, Champlain A, et al. Effect of platelet-rich plasma injection for rejuvenation of photoaged facial skin: A randomized clinical trial. JAMA Dermatol, 2018, 154(12): 1447-1452.
6.	Wu J, Piao Y, Liu Q, et al. Platelet-rich plasma-derived extracellular vesicles: A superior alternative in regenerative medicine? Cell Prolif, 2021, 54(12): e13123. doi: 10.1111/cpr.13123.
7.	Li Y, Xiao Q, Tang J, et al. Extracellular vesicles: Emerging therapeutics in cutaneous lesions. Int J Nanomedicine, 2021, 16: 6183-6202.
8.	Dixson AC, Dawson TR, Di Vizio D, et al. Context-specific regulation of extracellular vesicle biogenesis and cargo selection. Nat Rev Mol Cell Biol, 2023, 24(7): 454-476.
9.	袁霆, 何能斌, 丁堅, 等. 胞外囊泡在富血小板血漿修復組織中的作用. 中華關節外科雜志 (電子版), 2016, 10(6): 661-664.
10.	Wang Z, Zhou X, Kong Q, et al. Extracellular vesicle preparation and analysis: A state-of-the-art review. Adv Sci (Weinh), 2024, 11(30): e2401069. doi: 10.1002/advs.202401069.
11.	Yá?ez-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles, 2015, 4: 27066. doi: 10.3402/jev.v4.27066.
12.	Nieuwland R, Siljander PR. A beginner’s guide to study extracellular vesicles in human blood plasma and serum. J Extracell Vesicles, 2024, 13(1): e12400. doi: 10.1002/jev2.12400.
13.	Puhm F, Boilard E, Machlus KR. Platelet extracellular vesicles: Beyond the blood. Arterioscler Thromb Vasc Biol, 2021, 41(1): 87-96.
14.	Heijnen HF, Schiel AE, Fijnheer R, et al. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood, 1999, 94(11): 3791-3799.
15.	Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol, 1967, 13(3): 269-288.
16.	Warren BA, Vales O. The release of vesicles from platelets following adhesion to vessel walls in vitro. Br J Exp Pathol, 1972, 53(2): 206-215.
17.	Zhang Y, Wang X, Chen J, et al. Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis. J Nanobiotechnology, 2022, 20(1): 56. doi: 10.1186/s12951-022-01245-8.
18.	Hirayu N, Takasu O. Exploring the hemostatic effects of platelet lysate-derived vesicles: Insights from mouse models. Int J Mol Sci, 2024, 25(2): 1188. doi: 10.3390/ijms25021188.
19.	Sinauridze EI, Kireev DA, Popenko NY, et al. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost, 2007, 97(3): 425-434.
20.	Tripisciano C, Weiss R, Karuthedom George S, et al. Extracellular vesicles derived from platelets, red blood cells, and monocyte-like cells differ regarding their ability to induce factor Ⅻ dependent thrombin generation. Front Cell Dev Biol, 2020, 8: 298. doi: 10.3389/fcell.2020.00298.
21.	Suades R, Padró T, Vilahur G, et al. Platelet-released extracellular vesicles: the effects of thrombin activation. Cell Mol Life Sci, 2022, 79(3): 190. doi: 10.1007/s00018-022-04222-4.
22.	Miyazawa B, Trivedi A, Togarrati PP, et al. Regulation of endothelial cell permeability by platelet-derived extracellular vesicles. J Trauma Acute Care Surg, 2019, 86(6): 931-942.
23.	Yin B, Ni J, Witherel CE, et al. Harnessing tissue-derived extracellular vesicles for osteoarthritis theranostics. Theranostics, 2022, 12(1): 207-231.
24.	Adamczyk AM, Leicaj ML, Fabiano MP, et al. Extracellular vesicles from human plasma dampen inflammation and promote tissue repair functions in macrophages. J Extracell Vesicles, 2023, 12(6): e12331. doi: 10.1002/jev2.12331.
25.	Liu C, Yalavarthi S, Tambralli A, et al. Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice. Sci Adv, 2023, 9(43): eadj1019. doi: 10.1126/sciadv.adj1019.
26.	Rui S, Dai L, Zhang X, et al. Exosomal miRNA-26b-5p from PRP suppresses NETs by targeting MMP-8 to promote diabetic wound healing. J Control Release, 2024, 372: 221-233.
27.	Kim HK, Song KS, Chung JH, et al. Platelet microparticles induce angiogenesis in vitro. Br J Haematol, 2004, 124(3): 376-384.
28.	Sun Y, Liu XL, Zhang D, et al. Platelet-derived exosomes affect the proliferation and migration of human umbilical vein endothelial cells via miR-126. Curr Vasc Pharmacol, 2019, 17(4): 379-387.
29.	Brill A, Dashevsky O, Rivo J, et al. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res, 2005, 67(1): 30-38.
30.	Hayon Y, Dashevsky O, Shai E, et al. Platelet microparticles induce angiogenesis and neurogenesis after cerebral ischemia. Curr Neurovasc Res, 2012, 9(3): 185-192.
31.	Tao SC, Yuan T, Rui BY, et al. Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway. Theranostics, 2017, 7(3): 733-750.
32.	Guo SC, Tao SC, Yin WJ, et al. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model. Theranostics, 2017, 7(1): 81-96.
33.	Bian D, Wu Y, Song G, et al. The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review. Stem Cell Res Ther, 2022, 13(1): 24. doi: 10.1186/s13287-021-02697-9.
34.	Torreggiani E, Perut F, Roncuzzi L, et al. Exosomes: novel effectors of human platelet lysate activity. Eur Cell Mater, 2014, discussion 151. doi: 10.22203/ecm.v028a11.
35.	Chen T, Song P, He M, et al. Sphingosine-1-phosphate derived from PRP-Exos promotes angiogenesis in diabetic wound healing via the S1PR1/AKT/FN1 signalling pathway. Burns Trauma, 2023, 11: tkad003. doi: 10.1093/burnst/tkad003.
36.	Zhang Y, Yi D, Hong Q, et al. Platelet-rich plasma-derived exosomes enhance mesenchymal stem cell paracrine function and nerve regeneration potential. Biochem Biophys Res Commun, 2024, 699: 149496. doi: 10.1016/j.bbrc.2024.149496.
37.	Chen D, Tang Q, Song W, et al. Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats. J Orthop Surg Res, 2024, 19(1): 382. doi: 10.1186/s13018-024-04869-8.
38.	Wang L, Huang Y, Wu Y, et al. Platelet-derived extracellular vesicles promote hair follicle growth through β-catenin signaling pathway. Platelets, 2025, 36(1): 2498353. doi: 10.1080/09537104.2025.2498353.
39.	Tao X, Xue F, Xu J, et al. Platelet-rich plasma-derived extracellular vesicles inhibit NF-κB/NLRP3 pathway-mediated pyroptosis in intervertebral disc degeneration via the MALAT1/microRNA-217/SIRT1 axis. Cell Signal, 2024, 117: 111106. doi: 10.1016/j.cellsig.2024.111106.
40.	Hu B, Wang L, Sun N, et al. Mechanism of MIR-25-3P carried by extracellular vesicles derived from platelet-rich plasma in IL-1β-induced nucleus pulposus cell degeneration via the SOX4/CXCR7 axis. Shock, 2022, 58(1): 56-67.
41.	Cao W, Meng X, Cao F, et al. Exosomes derived from platelet-rich plasma promote diabetic wound healing via the JAK2/STAT3 pathway. iScience, 2023, 26(11): 108236. doi: 10.1016/j.isci.2023.108236.
42.	Xu Y, Lin Z, He L, et al. Platelet-rich plasma-derived exosomal USP15 promotes cutaneous wound healing via deubiquitinating EIF4A1. Oxid Med Cell Longev, 2021, 2021: 9674809. doi: 10.1155/2021/9674809.
43.	Burnouf T, Chou ML, Lundy DJ, et al. Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery. J Biomed Sci, 2023, 30(1): 79. doi: 10.1186/s12929-023-00972-w.
44.	Johnson J, Wu YW, Blyth C, et al. Prospective therapeutic applications of platelet extracellular vesicles. Trends Biotechnol, 2021, 39(6): 598-612.
45.	Johnson J, Law SQK, Shojaee M, et al. First-in-human clinical trial of allogeneic, platelet-derived extracellular vesicles as a potential therapeutic for delayed wound healing. J Extracell Vesicles, 2023, 12(7): e12332. doi: 10.1002/jev2.12332.
46.	李嬌, 李曉豐, 李劍平. 富血小板血漿來源的血小板細胞外囊泡分離技術與應用. 中國組織工程研究, 2025, 29(1): 156-163.
47.	華山, 張弘一, 顧嘉偉, 等. 富血小板血漿來源細胞外囊泡治療慢性創面的研究現狀及面臨的挑戰. 中華醫學美學美容雜志, 2025, 31(4): 337-342.

1. Kim HY, Kwon S, Um W, et al. Functional extracellular vesicles for regenerative medicine. Small, 2022, 18(36): e2106569. doi: 10.1002/smll.202106569.
2. Katz JN. Platelet-rich plasma for osteoarthritis and achilles tendinitis. JAMA, 2021, 326(20): 2012-2014.
3. Anitua E, Fernández-de-Retana S, Alkhraisat MH. Platelet rich plasma in oral and maxillofacial surgery from the perspective of composition. Platelets, 2021, 32(2): 174-182.
4. Gentile P, Calabrese C, De Angelis B, et al. Impact of the different preparation methods to obtain autologous non-activated platelet-rich plasma (A-PRP) and activated platelet-rich plasma (AA-PRP) in plastic surgery: Wound healing and hair regrowth evaluation. Int J Mol Sci, 2020, 21(2): 431. doi: 10.3390/ijms21020431.
5. Alam M, Hughart R, Champlain A, et al. Effect of platelet-rich plasma injection for rejuvenation of photoaged facial skin: A randomized clinical trial. JAMA Dermatol, 2018, 154(12): 1447-1452.
6. Wu J, Piao Y, Liu Q, et al. Platelet-rich plasma-derived extracellular vesicles: A superior alternative in regenerative medicine? Cell Prolif, 2021, 54(12): e13123. doi: 10.1111/cpr.13123.
7. Li Y, Xiao Q, Tang J, et al. Extracellular vesicles: Emerging therapeutics in cutaneous lesions. Int J Nanomedicine, 2021, 16: 6183-6202.
8. Dixson AC, Dawson TR, Di Vizio D, et al. Context-specific regulation of extracellular vesicle biogenesis and cargo selection. Nat Rev Mol Cell Biol, 2023, 24(7): 454-476.
9. 袁霆, 何能斌, 丁堅, 等. 胞外囊泡在富血小板血漿修復組織中的作用. 中華關節外科雜志 (電子版), 2016, 10(6): 661-664.
10. Wang Z, Zhou X, Kong Q, et al. Extracellular vesicle preparation and analysis: A state-of-the-art review. Adv Sci (Weinh), 2024, 11(30): e2401069. doi: 10.1002/advs.202401069.
11. Yá?ez-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles, 2015, 4: 27066. doi: 10.3402/jev.v4.27066.
12. Nieuwland R, Siljander PR. A beginner’s guide to study extracellular vesicles in human blood plasma and serum. J Extracell Vesicles, 2024, 13(1): e12400. doi: 10.1002/jev2.12400.
13. Puhm F, Boilard E, Machlus KR. Platelet extracellular vesicles: Beyond the blood. Arterioscler Thromb Vasc Biol, 2021, 41(1): 87-96.
14. Heijnen HF, Schiel AE, Fijnheer R, et al. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood, 1999, 94(11): 3791-3799.
15. Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol, 1967, 13(3): 269-288.
16. Warren BA, Vales O. The release of vesicles from platelets following adhesion to vessel walls in vitro. Br J Exp Pathol, 1972, 53(2): 206-215.
17. Zhang Y, Wang X, Chen J, et al. Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis. J Nanobiotechnology, 2022, 20(1): 56. doi: 10.1186/s12951-022-01245-8.
18. Hirayu N, Takasu O. Exploring the hemostatic effects of platelet lysate-derived vesicles: Insights from mouse models. Int J Mol Sci, 2024, 25(2): 1188. doi: 10.3390/ijms25021188.
19. Sinauridze EI, Kireev DA, Popenko NY, et al. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost, 2007, 97(3): 425-434.
20. Tripisciano C, Weiss R, Karuthedom George S, et al. Extracellular vesicles derived from platelets, red blood cells, and monocyte-like cells differ regarding their ability to induce factor Ⅻ dependent thrombin generation. Front Cell Dev Biol, 2020, 8: 298. doi: 10.3389/fcell.2020.00298.
21. Suades R, Padró T, Vilahur G, et al. Platelet-released extracellular vesicles: the effects of thrombin activation. Cell Mol Life Sci, 2022, 79(3): 190. doi: 10.1007/s00018-022-04222-4.
22. Miyazawa B, Trivedi A, Togarrati PP, et al. Regulation of endothelial cell permeability by platelet-derived extracellular vesicles. J Trauma Acute Care Surg, 2019, 86(6): 931-942.
23. Yin B, Ni J, Witherel CE, et al. Harnessing tissue-derived extracellular vesicles for osteoarthritis theranostics. Theranostics, 2022, 12(1): 207-231.
24. Adamczyk AM, Leicaj ML, Fabiano MP, et al. Extracellular vesicles from human plasma dampen inflammation and promote tissue repair functions in macrophages. J Extracell Vesicles, 2023, 12(6): e12331. doi: 10.1002/jev2.12331.
25. Liu C, Yalavarthi S, Tambralli A, et al. Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice. Sci Adv, 2023, 9(43): eadj1019. doi: 10.1126/sciadv.adj1019.
26. Rui S, Dai L, Zhang X, et al. Exosomal miRNA-26b-5p from PRP suppresses NETs by targeting MMP-8 to promote diabetic wound healing. J Control Release, 2024, 372: 221-233.
27. Kim HK, Song KS, Chung JH, et al. Platelet microparticles induce angiogenesis in vitro. Br J Haematol, 2004, 124(3): 376-384.
28. Sun Y, Liu XL, Zhang D, et al. Platelet-derived exosomes affect the proliferation and migration of human umbilical vein endothelial cells via miR-126. Curr Vasc Pharmacol, 2019, 17(4): 379-387.
29. Brill A, Dashevsky O, Rivo J, et al. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res, 2005, 67(1): 30-38.
30. Hayon Y, Dashevsky O, Shai E, et al. Platelet microparticles induce angiogenesis and neurogenesis after cerebral ischemia. Curr Neurovasc Res, 2012, 9(3): 185-192.
31. Tao SC, Yuan T, Rui BY, et al. Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway. Theranostics, 2017, 7(3): 733-750.
32. Guo SC, Tao SC, Yin WJ, et al. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model. Theranostics, 2017, 7(1): 81-96.
33. Bian D, Wu Y, Song G, et al. The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review. Stem Cell Res Ther, 2022, 13(1): 24. doi: 10.1186/s13287-021-02697-9.
34. Torreggiani E, Perut F, Roncuzzi L, et al. Exosomes: novel effectors of human platelet lysate activity. Eur Cell Mater, 2014, discussion 151. doi: 10.22203/ecm.v028a11.
35. Chen T, Song P, He M, et al. Sphingosine-1-phosphate derived from PRP-Exos promotes angiogenesis in diabetic wound healing via the S1PR1/AKT/FN1 signalling pathway. Burns Trauma, 2023, 11: tkad003. doi: 10.1093/burnst/tkad003.
36. Zhang Y, Yi D, Hong Q, et al. Platelet-rich plasma-derived exosomes enhance mesenchymal stem cell paracrine function and nerve regeneration potential. Biochem Biophys Res Commun, 2024, 699: 149496. doi: 10.1016/j.bbrc.2024.149496.
37. Chen D, Tang Q, Song W, et al. Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats. J Orthop Surg Res, 2024, 19(1): 382. doi: 10.1186/s13018-024-04869-8.
38. Wang L, Huang Y, Wu Y, et al. Platelet-derived extracellular vesicles promote hair follicle growth through β-catenin signaling pathway. Platelets, 2025, 36(1): 2498353. doi: 10.1080/09537104.2025.2498353.
39. Tao X, Xue F, Xu J, et al. Platelet-rich plasma-derived extracellular vesicles inhibit NF-κB/NLRP3 pathway-mediated pyroptosis in intervertebral disc degeneration via the MALAT1/microRNA-217/SIRT1 axis. Cell Signal, 2024, 117: 111106. doi: 10.1016/j.cellsig.2024.111106.
40. Hu B, Wang L, Sun N, et al. Mechanism of MIR-25-3P carried by extracellular vesicles derived from platelet-rich plasma in IL-1β-induced nucleus pulposus cell degeneration via the SOX4/CXCR7 axis. Shock, 2022, 58(1): 56-67.
41. Cao W, Meng X, Cao F, et al. Exosomes derived from platelet-rich plasma promote diabetic wound healing via the JAK2/STAT3 pathway. iScience, 2023, 26(11): 108236. doi: 10.1016/j.isci.2023.108236.
42. Xu Y, Lin Z, He L, et al. Platelet-rich plasma-derived exosomal USP15 promotes cutaneous wound healing via deubiquitinating EIF4A1. Oxid Med Cell Longev, 2021, 2021: 9674809. doi: 10.1155/2021/9674809.
43. Burnouf T, Chou ML, Lundy DJ, et al. Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery. J Biomed Sci, 2023, 30(1): 79. doi: 10.1186/s12929-023-00972-w.
44. Johnson J, Wu YW, Blyth C, et al. Prospective therapeutic applications of platelet extracellular vesicles. Trends Biotechnol, 2021, 39(6): 598-612.
45. Johnson J, Law SQK, Shojaee M, et al. First-in-human clinical trial of allogeneic, platelet-derived extracellular vesicles as a potential therapeutic for delayed wound healing. J Extracell Vesicles, 2023, 12(7): e12332. doi: 10.1002/jev2.12332.
46. 李嬌, 李曉豐, 李劍平. 富血小板血漿來源的血小板細胞外囊泡分離技術與應用. 中國組織工程研究, 2025, 29(1): 156-163.
47. 華山, 張弘一, 顧嘉偉, 等. 富血小板血漿來源細胞外囊泡治療慢性創面的研究現狀及面臨的挑戰. 中華醫學美學美容雜志, 2025, 31(4): 337-342.

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Latest ArticlesResearch progress on extracellular vesicles derived from platelet-rich plasma in tissue injury repair and regeneration

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