Progress and challenges of poly (<i>L</i>-lactic acid) membrane in preventing tendon adhesion_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

ZHANG Jiayu , HU Xiaobei , SHEN Jiayan , HUANG Yuanji ,  LIU Shen

Department of Orthopedics, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, 200233, P. R. China;

Corresponding author：

LIU Shen, Email: liushen@126.com

Keywords：

Poly (L-lactic acid); tendon anti-adhesion; mechanical adaptation; organizational adaptation; degradation adaptation; biomaterials

DOI：

10.7507/1002-1892.202505003

Video：

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Objective To review the research progress and challenges of poly (L-lactic acid) (PLLA) membrane in preventing tendon adhesion. Methods The relevant literature at home and abroad in recent years was extensively searched, covering the mechanism of tendon adhesion formation, the adaptation challenge and balancing strategy of PLLA, the physicochemical modification of PLLA anti-adhesion membrane and its application in tendon anti-adhesion. In this paper, the research progress and modification strategies of PLLA films are systematically reviewed from the three dimensions of tissue adaptation, mechanical adaptation and degradation adaptation. Results The three-dimensional fitness of PLLA membrane is optimized by combining materials (such as hydroxyapatite, polycaprolactone), structural design (multilayer/gradient membrane), and drug loading (anti-inflammatory drug). The balance between anti-adhesion and pro-healing is achieved, the mechanical fitness is significantly improved, and degradation fitness achieved (targeting the degradation cycle to 2-4 weeks to cover the tendon repair period). Conclusion In the future, it is necessary to identify the optimal balance point of three-dimensional fitness, unify the evaluation criteria and solve the degradation side effects through the co-design of physicochemical modification and drug loading system to break through the bottleneck of clinical translation.

1.	Titan AL, Foster DS, Chang J, et al. Flexor tendon: Development, healing, adhesion formation, and contributing growth factors. Plast Reconstr Surg, 2019, 144(4): 639e-647e.
2.	de Jong JP, Nguyen JT, Sonnema AJ, et al. The incidence of acute traumatic tendon injuries in the hand and wrist: a 10-year population-based study. Clin Orthop Surg, 2014, 6(2): 196-202.
3.	Zhu Y, Zhang C, Liang Y, et al. Advanced postoperative tissue antiadhesive membranes enabled with electrospun nanofibers. Biomater Sci, 2024, 12(7): 1643-1661.
4.	Collen D, Lijnen HR. Molecular basis of fibrinolysis, as relevant for thrombolytic therapy. Thromb Haemost, 1995, 74(1): 167-171.
5.	Voleti PB, Buckley MR, Soslowsky LJ. Tendon healing: repair and regeneration. Annu Rev Biomed Eng, 2012, 14: 47-71.
6.	Walden G, Liao X, Donell S, et al. A Clinical, biological, and biomaterials perspective into tendon injuries and regeneration. Tissue Eng Part B Rev, 2017, 23(1): 44-58.
7.	Bhavsar D, Shettko D, Tenenhaus M. Encircling the tendon repair site with collagen-GAG reduces the formation of postoperative tendon adhesions in a chicken flexor tendon model. J Surg Res, 2010, 159(2): 765-771.
8.	Postlethwaite AE, Keski-Oja J, Moses HL, et al. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med, 1987, 165(1): 251-256.
9.	Wahl SM, Hunt DA, Wakefield LM, et al. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A, 1987, 84(16): 5788-5792.
10.	Chisari E, Rehak L, Khan WS, et al. The role of the immune system in tendon healing: a systematic review. Br Med Bull, 2020, 133(1): 49-64.
11.	Wei Y, Yun X, Guan Y, et al. Wnt3a-modified nanofiber scaffolds facilitate tendon healing by driving macrophage polarization during repair. ACS Appl Mater Interfaces, 2023. doi: 10.1021/acsami.2c20386.
12.	Wang S, Xiao Y, Tian J, et al. Targeted macrophage CRISPR-Cas13 mRNA editing in immunotherapy for tendon injury. Adv Mater, 2024, 36(19): e2311964. doi: 10.1002/adma.202311964.
13.	Liao J, Li X, Fan Y. Prevention strategies of postoperative adhesion in soft tissues by applying biomaterials: Based on the mechanisms of occurrence and development of adhesions. Bioact Mater, 2023, 26: 387-412.
14.	Ao YJ, Yi Y, Wu GH. Application of PLLA (poly-L-lactic acid) for rejuvenation and reproduction of facial cutaneous tissue in aesthetics: A review. Medicine (Baltimore), 2024, 103(11): e37506. doi: 10.1097/MD.0000000000037506.
15.	Yang Y, Yao Z, Sun Y, et al. 3D-printed manganese dioxide incorporated scaffold promotes osteogenic-angiogenic coupling for refractory bone defect by remodeling osteo-regenerative microenvironment. Bioact Mater, 2024, 44: 354-370.
16.	Ju J, Peng X, Huang K, et al. High-performance porous PLLA-based scaffolds for bone tissue engineering: Preparation, characterization, and in vitro and in vivo evaluation. Polymer, 2019, 180: 121707. doi: 10.1016/j.polymer.2019.121707.
17.	Zhu Y, Liang H, Liu X, et al. Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration. Sci Adv, 2021, 7(14): eabf6654. doi: 10.1126/sciadv.abf6654.
18.	Xie X, Xu J, Ding D, et al. Janus membranes patch achieves high-quality tendon repair: Inhibiting exogenous healing and promoting endogenous healing. Nano Lett, 2024, 24(14): 4300-4309.
19.	Liu R, He T, Li R, et al. Comparison of different types of poly-L-lactic acid microspheres in vitro and in vivo studies. Aesthet Surg J Open Forum, 2024, 6: ojae091. doi: 10.1093/asjof/ojae091.
20.	Qu X, Sang X, Lv Y, et al. PLLA-COI multilayer nanofiber membrane for anti-adhesion of the Achilles tendon. Materials Today Communications, 2024, 38: 107595. doi: 10.1016/j.mtcomm.2023.107595.
21.	中国科学院大学深圳医院 (光明). 一种复合肌腱防粘连膜及制备方法: 202010574129.9[P]. 2020-09-29.
22.	Mao Y, Guidoin R, Brochu G, et al. Facile fabrication of phospholipid-functionalized nanofiber-based barriers with enhanced anti-adhesion efficiency. Colloids Surf B Biointerfaces, 2021, 203: 111728. doi: 10.1016/j.colsurfb.2021.111728.
23.	Srihanam P, Thongsomboon W, Baimark Y. Phase morphology, mechanical, and thermal properties of calcium carbonate-reinforced poly (L-lactide)-b-poly (ethylene glycol)-b-poly (L-lactide) bioplastics. Polymers (Basel), 2023, 15(2): 301. doi: 10.3390/polym15020301.
24.	Shuai C, Yang F, Shuai Y, et al. Silicon dioxide nanoparticles decorated on graphene oxide nanosheets and their application in poly (L-lactic acid) scaffold. J Adv Res, 2023, 48: 175-190.
25.	Khodabandeh A, Yousefi AA, Jafarzadeh-Holagh S, et al. Fabrication of 3D microfibrous composite polycaprolactone/hydroxyapatite scaffolds loaded with piezoelectric poly (lactic acid) nanofibers by sequential near-field and conventional electrospinning for bone tissue engineering. Biomater Adv, 2025, 166: 214053. doi: 10.1016/j.bioadv.2024.214053.
26.	Tao Y, Jiao G, Zhao X, et al. Amino acid-crosslinked 4arm-PLGA Janus patch with anti-adhesive and anti-bacterial properties for hernia repair. Colloids Surf B Biointerfaces, 2024, 243: 114126. doi: 10.1016/j.colsurfb.2024.114126.
27.	Liu J, Li T, Zhang H, et al. Electrospun strong, bioactive, and bioabsorbable silk fibroin/poly (L-lactic-acid) nanoyarns for constructing advanced nanotextile tissue scaffolds. Mater Today Bio, 2022, 14: 100243. doi: 10.1016/j.mtbio.2022.100243.
28.	北京化工大学. 一种成分梯度化肌腱防粘连纤维膜及其制备方法: 202110264223.9[P]. 2021-06-25.
29.	Xuan H, Zhang Z, Jiang W, et al. Dual-bioactive molecules loaded aligned core-shell microfibers for tendon tissue engineering. Colloids Surf B Biointerfaces, 2023, 228: 113416. doi: 10.1016/j.colsurfb.2023.113416.
30.	Lin X, Qi SL, Hai BW, et al. Electrospun multi-functional medicated tri-section Janus nanofibers for an improved anti-adhesion tendon repair. Chemical Engineering Journal, 2024, 492: 152359. doi: 10.1016/j.cej.2024.152359.
31.	Zhang Q, Yang Y, Suo D, et al. A biomimetic adhesive and robust janus patch with anti-oxidative, anti-inflammatory, and anti-bacterial activities for tendon repair. ACS Nano, 2023, 17(17): 16798-16816.
32.	Capuana E, Lopresti F, Ceraulo M, et al. Poly-L-lactic acid (PLLA)-based biomaterials for regenerative medicine: A review on processing and applications. Polymers (Basel), 2022, 14(6): 1153. doi: 10.3390/polym14061153.
33.	He T, Zhang Z, Zhang X, et al. Effects of poly-L-lactic acid fillers on inflammatory response and collagen synthesis in different animal models. J Cosmet Dermatol, 2025, 24(2): e70000. doi: 10.1111/jocd.70000. v. doi: 10.1111/jocd.70000.v.
34.	Zhou X, Kong R, Deng F, et al. Self- delivery photothermal converter for feedback enhanced tumor therapy by cascade inflammation inhibition. Chem Eng J, 2023, 453(2): 139887. doi: 10.1016/j.cej.2022.139887.
35.	Liu J, Tang R, Zhu X, et al. Ibuprofen-loaded bilayer electrospun mesh modulates host response toward promoting full-thickness abdominal wall defect repair. J Biomed Mater Res A, 2024, 112(6): 941-955.
36.	刘珅. 一种三层复合结构肌腱术后仿生腱鞘防粘连膜: CN 115554479 A [P]. 2023-01-03.
37.	Deng J, Yao Z, Wang S, et al. Uni-directional release of ibuprofen from an asymmetric fibrous membrane enables effective peritendinous anti-adhesion. J Control Release, 2024, 372: 251-264.
38.	Zeng X, Li Y, Zhao G, et al. Dipyridamole-grafted copolymer electrospun nanofiber membranes for suppression of peritendinous adhesions. Acta Biomater, 2024, 188: 197-211.
39.	Li Y, Hu C, Hu B, et al. Sustained release of dicumarol via novel grafted polymer in electrospun nanofiber membrane for treatment of peritendinous adhesion. Adv Healthc Mater, 2023, 12(15): e2203078. doi: 10.1002/adhm.202203078.
40.	Xiao Y, Tao Z, Ju Y, et al. Diamond-like carbon depositing on the surface of polylactide membrane for prevention of adhesion formation during tendon repair. Nanomicro Lett, 2024, 16(1): 186. doi: 10.1007/s40820-024-01392-7.

1. Titan AL, Foster DS, Chang J, et al. Flexor tendon: Development, healing, adhesion formation, and contributing growth factors. Plast Reconstr Surg, 2019, 144(4): 639e-647e.
2. de Jong JP, Nguyen JT, Sonnema AJ, et al. The incidence of acute traumatic tendon injuries in the hand and wrist: a 10-year population-based study. Clin Orthop Surg, 2014, 6(2): 196-202.
3. Zhu Y, Zhang C, Liang Y, et al. Advanced postoperative tissue antiadhesive membranes enabled with electrospun nanofibers. Biomater Sci, 2024, 12(7): 1643-1661.
4. Collen D, Lijnen HR. Molecular basis of fibrinolysis, as relevant for thrombolytic therapy. Thromb Haemost, 1995, 74(1): 167-171.
5. Voleti PB, Buckley MR, Soslowsky LJ. Tendon healing: repair and regeneration. Annu Rev Biomed Eng, 2012, 14: 47-71.
6. Walden G, Liao X, Donell S, et al. A Clinical, biological, and biomaterials perspective into tendon injuries and regeneration. Tissue Eng Part B Rev, 2017, 23(1): 44-58.
7. Bhavsar D, Shettko D, Tenenhaus M. Encircling the tendon repair site with collagen-GAG reduces the formation of postoperative tendon adhesions in a chicken flexor tendon model. J Surg Res, 2010, 159(2): 765-771.
8. Postlethwaite AE, Keski-Oja J, Moses HL, et al. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med, 1987, 165(1): 251-256.
9. Wahl SM, Hunt DA, Wakefield LM, et al. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A, 1987, 84(16): 5788-5792.
10. Chisari E, Rehak L, Khan WS, et al. The role of the immune system in tendon healing: a systematic review. Br Med Bull, 2020, 133(1): 49-64.
11. Wei Y, Yun X, Guan Y, et al. Wnt3a-modified nanofiber scaffolds facilitate tendon healing by driving macrophage polarization during repair. ACS Appl Mater Interfaces, 2023. doi: 10.1021/acsami.2c20386.
12. Wang S, Xiao Y, Tian J, et al. Targeted macrophage CRISPR-Cas13 mRNA editing in immunotherapy for tendon injury. Adv Mater, 2024, 36(19): e2311964. doi: 10.1002/adma.202311964.
13. Liao J, Li X, Fan Y. Prevention strategies of postoperative adhesion in soft tissues by applying biomaterials: Based on the mechanisms of occurrence and development of adhesions. Bioact Mater, 2023, 26: 387-412.
14. Ao YJ, Yi Y, Wu GH. Application of PLLA (poly-L-lactic acid) for rejuvenation and reproduction of facial cutaneous tissue in aesthetics: A review. Medicine (Baltimore), 2024, 103(11): e37506. doi: 10.1097/MD.0000000000037506.
15. Yang Y, Yao Z, Sun Y, et al. 3D-printed manganese dioxide incorporated scaffold promotes osteogenic-angiogenic coupling for refractory bone defect by remodeling osteo-regenerative microenvironment. Bioact Mater, 2024, 44: 354-370.
16. Ju J, Peng X, Huang K, et al. High-performance porous PLLA-based scaffolds for bone tissue engineering: Preparation, characterization, and in vitro and in vivo evaluation. Polymer, 2019, 180: 121707. doi: 10.1016/j.polymer.2019.121707.
17. Zhu Y, Liang H, Liu X, et al. Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration. Sci Adv, 2021, 7(14): eabf6654. doi: 10.1126/sciadv.abf6654.
18. Xie X, Xu J, Ding D, et al. Janus membranes patch achieves high-quality tendon repair: Inhibiting exogenous healing and promoting endogenous healing. Nano Lett, 2024, 24(14): 4300-4309.
19. Liu R, He T, Li R, et al. Comparison of different types of poly-L-lactic acid microspheres in vitro and in vivo studies. Aesthet Surg J Open Forum, 2024, 6: ojae091. doi: 10.1093/asjof/ojae091.
20. Qu X, Sang X, Lv Y, et al. PLLA-COI multilayer nanofiber membrane for anti-adhesion of the Achilles tendon. Materials Today Communications, 2024, 38: 107595. doi: 10.1016/j.mtcomm.2023.107595.
21. 中国科学院大学深圳医院 (光明). 一种复合肌腱防粘连膜及制备方法: 202010574129.9[P]. 2020-09-29.
22. Mao Y, Guidoin R, Brochu G, et al. Facile fabrication of phospholipid-functionalized nanofiber-based barriers with enhanced anti-adhesion efficiency. Colloids Surf B Biointerfaces, 2021, 203: 111728. doi: 10.1016/j.colsurfb.2021.111728.
23. Srihanam P, Thongsomboon W, Baimark Y. Phase morphology, mechanical, and thermal properties of calcium carbonate-reinforced poly (L-lactide)-b-poly (ethylene glycol)-b-poly (L-lactide) bioplastics. Polymers (Basel), 2023, 15(2): 301. doi: 10.3390/polym15020301.
24. Shuai C, Yang F, Shuai Y, et al. Silicon dioxide nanoparticles decorated on graphene oxide nanosheets and their application in poly (L-lactic acid) scaffold. J Adv Res, 2023, 48: 175-190.
25. Khodabandeh A, Yousefi AA, Jafarzadeh-Holagh S, et al. Fabrication of 3D microfibrous composite polycaprolactone/hydroxyapatite scaffolds loaded with piezoelectric poly (lactic acid) nanofibers by sequential near-field and conventional electrospinning for bone tissue engineering. Biomater Adv, 2025, 166: 214053. doi: 10.1016/j.bioadv.2024.214053.
26. Tao Y, Jiao G, Zhao X, et al. Amino acid-crosslinked 4arm-PLGA Janus patch with anti-adhesive and anti-bacterial properties for hernia repair. Colloids Surf B Biointerfaces, 2024, 243: 114126. doi: 10.1016/j.colsurfb.2024.114126.
27. Liu J, Li T, Zhang H, et al. Electrospun strong, bioactive, and bioabsorbable silk fibroin/poly (L-lactic-acid) nanoyarns for constructing advanced nanotextile tissue scaffolds. Mater Today Bio, 2022, 14: 100243. doi: 10.1016/j.mtbio.2022.100243.
28. 北京化工大学. 一种成分梯度化肌腱防粘连纤维膜及其制备方法: 202110264223.9[P]. 2021-06-25.
29. Xuan H, Zhang Z, Jiang W, et al. Dual-bioactive molecules loaded aligned core-shell microfibers for tendon tissue engineering. Colloids Surf B Biointerfaces, 2023, 228: 113416. doi: 10.1016/j.colsurfb.2023.113416.
30. Lin X, Qi SL, Hai BW, et al. Electrospun multi-functional medicated tri-section Janus nanofibers for an improved anti-adhesion tendon repair. Chemical Engineering Journal, 2024, 492: 152359. doi: 10.1016/j.cej.2024.152359.
31. Zhang Q, Yang Y, Suo D, et al. A biomimetic adhesive and robust janus patch with anti-oxidative, anti-inflammatory, and anti-bacterial activities for tendon repair. ACS Nano, 2023, 17(17): 16798-16816.
32. Capuana E, Lopresti F, Ceraulo M, et al. Poly-L-lactic acid (PLLA)-based biomaterials for regenerative medicine: A review on processing and applications. Polymers (Basel), 2022, 14(6): 1153. doi: 10.3390/polym14061153.
33. He T, Zhang Z, Zhang X, et al. Effects of poly-L-lactic acid fillers on inflammatory response and collagen synthesis in different animal models. J Cosmet Dermatol, 2025, 24(2): e70000. doi: 10.1111/jocd.70000. v. doi: 10.1111/jocd.70000.v.
34. Zhou X, Kong R, Deng F, et al. Self- delivery photothermal converter for feedback enhanced tumor therapy by cascade inflammation inhibition. Chem Eng J, 2023, 453(2): 139887. doi: 10.1016/j.cej.2022.139887.
35. Liu J, Tang R, Zhu X, et al. Ibuprofen-loaded bilayer electrospun mesh modulates host response toward promoting full-thickness abdominal wall defect repair. J Biomed Mater Res A, 2024, 112(6): 941-955.
36. 刘珅. 一种三层复合结构肌腱术后仿生腱鞘防粘连膜: CN 115554479 A [P]. 2023-01-03.
37. Deng J, Yao Z, Wang S, et al. Uni-directional release of ibuprofen from an asymmetric fibrous membrane enables effective peritendinous anti-adhesion. J Control Release, 2024, 372: 251-264.
38. Zeng X, Li Y, Zhao G, et al. Dipyridamole-grafted copolymer electrospun nanofiber membranes for suppression of peritendinous adhesions. Acta Biomater, 2024, 188: 197-211.
39. Li Y, Hu C, Hu B, et al. Sustained release of dicumarol via novel grafted polymer in electrospun nanofiber membrane for treatment of peritendinous adhesion. Adv Healthc Mater, 2023, 12(15): e2203078. doi: 10.1002/adhm.202203078.
40. Xiao Y, Tao Z, Ju Y, et al. Diamond-like carbon depositing on the surface of polylactide membrane for prevention of adhesion formation during tendon repair. Nanomicro Lett, 2024, 16(1): 186. doi: 10.1007/s40820-024-01392-7.

Chinese Journal of Reparative and Reconstructive Surgery

Latest ArticlesProgress and challenges of poly (L-lactic acid) membrane in preventing tendon adhesion

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