Skip to main content

Advertisement

Log in

Amnion-Based Biomaterials for Musculoskeletal Regenerative Engineering

  • Review
  • Published:
Regenerative Engineering and Translational Medicine Aims and scope Submit manuscript

Abstract

Purpose

Amnion is used as a biomaterial for musculoskeletal tissue regeneration due to its unique properties, including biocompatibility, low immunogenicity, anti-inflammatory, anti-fibrosis, and accelerating wound healing. In addition, the presence of stem cells within the amnion tissue further enriches the regenerative potential of this tissue. Although several decellularized amnion products are commercially available, the use of amnion for musculoskeletal tissue regeneration is a growing area of research. Concerns with isolation, preparation, processing, sterility, limited clinical evidence, and increased regulatory scrutiny of regenerative medicine therapies have created significant barriers in its clinical translation. This review paper aims to provide a comprehensive review of amnion structure, types of amnion-derived cells, biological properties, their mechanisms in various musculoskeletal tissue regeneration, and the current status of clinical translation of amnion-derived materials.

Methods

A search of Google Scholar and PubMed has been performed using a combination of keywords. A review of the characteristics of amnion is presented. Preclinical and clinical studies using amnion membrane or amnion-derived stem cells as biomaterials were summarized.

Results

Numerous articles have suggested the potential of amnion-based biomaterials for musculoskeletal tissue regeneration.

Conclusion

Considering the unique properties of amnion and its use in basic sciences, preclinical and clinical studies may lead to a breakthrough in regenerative engineering applications. Broader applications and extensive assessment of amnion use for tissue regeneration would require standardized preparation, processing, and storage methods followed by high-quality preclinical studies and randomized clinical trials.

Lay Summary

The amnion is a protective layer surrounding a developing fetus, and its unique properties have generated interest in using it as a biomaterial in musculoskeletal tissue regeneration. In addition, the presence of stem cells within the amnion tissue further enriches the regenerative potential of this tissue. However, concerns with isolation, preparation, processing, sterility, limited clinical evidence, and increased regulatory scrutiny of regenerative medicine therapies have created significant barriers in its clinical translation. Thus, broader applications and extensive assessment of amnion membrane and amnion-derived stem cells used for tissue regeneration would require standardized preparation, processing, and storage methods followed by high-quality preclinical studies and randomized clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. JW D. Skin transplantation with a review of 550 cases at the Johns Hopkins Hospital. Johns Hopkins Med J. 1910;15:96.

  2. Parolini O, Alviano F, Bagnara GP, Bilic G, Bühring H-J, Evangelista M, et al. Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells. 2008;26:300–11. https://doi.org/10.1634/stemcells.2007-0594.

    Article  Google Scholar 

  3. Escobar Ivirico JL, Bhattacharjee M, Kuyinu E, Nair LS, Laurencin CT. Regenerative engineering for knee osteoarthritis treatment: biomaterials and cell-based technologies. Engineer. 2017;3:16–27. https://doi.org/10.1016/J.ENG.2017.01.003.

    Article  Google Scholar 

  4. Yang L, Sun L, Zhang H, Bian F, Zhao Y. Ice-inspired lubricated drug delivery particles from microfluidic electrospray for osteoarthritis treatment. ACS Nano. 2021;15:20600–6. https://doi.org/10.1021/acsnano.1c09325.

    Article  CAS  Google Scholar 

  5. Lei Y, Zhang Q, Kuang G, Wang X, Fan Q, Ye F. Functional biomaterials for osteoarthritis treatment: from research to application. Smart Med. 2022:1. https://doi.org/10.1002/smmd.20220014.

  6. Yang L, Wang X, Yu Y, Shang L, Xu W, Zhao Y. Bio-inspired dual-adhesive particles from microfluidic electrospray for bone regeneration. Nano Res. 2023;16:5292–9. https://doi.org/10.1007/s12274-022-5202-9.

    Article  CAS  Google Scholar 

  7. Bennett JP, Matthews R, Faulk WP. Treatment of chronic ulceration of the legs with human amnion. Lancet. 1980;315:1153–6. https://doi.org/10.1016/S0140-6736(80)91616-5.

    Article  Google Scholar 

  8. Ke M, Cj D. Human amnion in the treatment of vaginal malformations. BJOG An Int J Obstet Gynaecol. 1986;93:50–4. https://doi.org/10.1111/j.1471-0528.1986.tb07813.x.

    Article  Google Scholar 

  9. Fernandes M, Sridhar MS, Sangwan VS, Rao GN. Amniotic membrane transplantation for ocular surface reconstruction. Cornea. 2005;24:643–53. https://doi.org/10.1097/01.ico.0000151501.80952.c5.

    Article  Google Scholar 

  10. Lee SH, Tseng SCG. Amniotic membrane transplantation for persistent epithelial defects with ulceration. Am J Ophthalmol. 1997;123:303–12. https://doi.org/10.1016/S0002-9394(14)70125-4.

    Article  CAS  Google Scholar 

  11. Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM. Properties of the amniotic membrane for potential use in tissue engineering. Eur Cells Mater. 2008;15:88–99. https://doi.org/10.22203/ecm.v015a07.

    Article  CAS  Google Scholar 

  12. Mamede AC, Carvalho MJ, Abrantes AM, Laranjo M, Maia CJ, Botelho MF. Amniotic membrane: from structure and functions to clinical applications. Cell Tissue Res. 2012;349:447–58. https://doi.org/10.1007/s00441-012-1424-6.

    Article  CAS  Google Scholar 

  13. Chopra A, Thomas BS. Amniotic membrane: a novel material for regeneration and repair. Biomimetics Biomater tissue Eng. 2013;18:1–8.

    Google Scholar 

  14. Insausti CL, Blanquer M, Bleda P, Iniesta P, Majado MJ, Castellanos G, et al. The amniotic membrane as a source of stem cells. Histol Histopathol. 2010;25:91–8. https://doi.org/10.14670/HH-25.91.

    Article  CAS  Google Scholar 

  15. Jahanafrooz Z, Bakhshandeh B, Behnam Abdollahi S, Seyedjafari E. Human amniotic membrane as a multifunctional biomaterial: recent advances and applications. J Biomater Appl. 2022;37:1341–54. https://doi.org/10.1177/08853282221137609.

    Article  CAS  Google Scholar 

  16. Fénelon M, Catros S, Meyer C, Fricain JC, Obert L, Auber F, et al. Applications of human amniotic membrane for tissue engineering. Membranes (Basel). 2021;11:387. https://doi.org/10.3390/membranes11060387.

    Article  CAS  Google Scholar 

  17. Rocha SCM, Maia Baptista CJ. Biochemical properties of amnioticmembrane. Amniotic Membr Orig Charact Med Appl. Dordrecht:Springer Netherlands 2015. 19–40

  18. Aplin JD, Campbell S, Allen TD. The extracellular matrix of human amniotic epithelium: ultrastructure, composition and deposition. J Cell Sci. 1985;79:119–36. https://doi.org/10.1242/jcs.79.1.119.

    Article  CAS  Google Scholar 

  19. Dua HS, Gomes JAP, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Surv Ophthalmol. 2004;49:51–77. https://doi.org/10.1016/j.survophthal.2003.10.004.

    Article  Google Scholar 

  20. Baradaran-Rafii A, Aghayan H-R, Arjmand B, Javadi M-A. Amniotic membrane transplantation. Iran J Ophthalmic Res. 2007;2:58–75.

    Google Scholar 

  21. Miki T, Lehmann T, Cai H, Stolz DB, Strom SC. Stem cell characteristics of amniotic epithelial cells. Stem Cells. 2005;23:1549–59. https://doi.org/10.1634/stemcells.2004-0357.

    Article  CAS  Google Scholar 

  22. Ilancheran S, Michalska A, Peh G, Wallace EM, Pera M, Manuelpillai U. Stem cells derived from human fetal membranes display multilineage differentiation potential. Biol Reprod. 2007;77:577–88. https://doi.org/10.1095/biolreprod.106.055244.

    Article  CAS  Google Scholar 

  23. Tamagawa T, Ishiwata I, Saito S. Establishment and characterization of a pluripotent stem cell line derived from human amniotic membranes and initiation of germ layers in vitro. Hum Cell. 2004;17:125–30. https://doi.org/10.1111/j.1749-0774.2004.tb00028.x.

    Article  Google Scholar 

  24. Zhang Y, Li C, Jiang X, Zhang S, Wu Y, Liu B, et al. Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells. Exp Hematol. 2004;32:657–64. https://doi.org/10.1016/j.exphem.2004.04.001.

    Article  CAS  Google Scholar 

  25. Kobayashi M, Yakuwa T, Sasaki K, Sato K, Kikuchi A, Kamo I, et al. Multilineage potential of side population cells from human amnion mesenchymal layer. Cell Transplant. 2008;17:291–301. https://doi.org/10.3727/096368908784153904.

    Article  CAS  Google Scholar 

  26. Portmann-Lanz CB, Schoeberlein A, Huber A, Sager R, Malek A, Holzgreve W, et al. Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am J Obstet Gynecol. 2006;194:664–73. https://doi.org/10.1016/j.ajog.2006.01.101.

    Article  CAS  Google Scholar 

  27. Solomon A, Rosenblatt M, Monroy D, Ji Z, Pflugfelder SC, Tseng SCG. Suppression of interleukin 1 α and interleukin 1 β in human limbal epithelial cells cultured on the amniotic membrane stromal matrix. Br J Ophthalmol. 2001;85:444–9. https://doi.org/10.1136/bjo.85.4.444.

    Article  CAS  Google Scholar 

  28. Hao Y, Ma DHK, Hwang DG, Kim WS, Zhang F. Identification of antiangiogenic and antiinflammatory proteins in human amniotic membrane. Cornea. 2000;19:348–52. https://doi.org/10.1097/00003226-200005000-00018.

    Article  CAS  Google Scholar 

  29. Kim JS, Kim JC, Na BK, Jeong JM, Song CY. Amniotic membrane patching promotes healing and inhibits proteinase activity on wound healing following acute corneal alkali burn. Exp Eye Res. 2000;70:329–37. https://doi.org/10.1006/exer.1999.0794.

    Article  CAS  Google Scholar 

  30. Higa K, Shimmura S, Shimazaki J, Tsubota K. Hyaluronic acid-CD44 interaction mediates the adhesion of lymphocytes by amniotic membrane stroma. Cornea. 2005;24:206–12. https://doi.org/10.1097/01.ico.0000133999.45262.83.

    Article  Google Scholar 

  31. Magatti M, Caruso M, De Munari S, Vertua E, De D, Manuelpillai U, et al. Human amniotic membrane-derived mesenchymal and epithelial cells exert different effects on monocyte-derived dendritic cell differentiation and function. Cell Transplant. 2015;24:1733–52. https://doi.org/10.3727/096368914X684033.

    Article  Google Scholar 

  32. Fairbairn NG, Randolph MA, Redmond RW. The clinical applications of human amnion in plastic surgery. J Plast Reconstr Aesthetic Surg. 2014;67:662–75. https://doi.org/10.1016/j.bjps.2014.01.031.

    Article  CAS  Google Scholar 

  33. Tseng SCG, Li DQ, Ma X. Suppression of transforming growth factor-beta isoforms, TGF-β receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. J Cell Physiol. 1999;179:325–35.

    Article  CAS  Google Scholar 

  34. Sant Anna LB, Cargnoni A, Ressel L, Vanosi G, Parolini O. Amniotic membrane application reduces liver fibrosis in a bile duct ligation rat model. Cell Transplant. 2011;20:441–53. https://doi.org/10.3727/096368910X522252.

    Article  Google Scholar 

  35. Koizumi N, Inatomi T, Sotozono C, Fullwood NJ, Quantock AJ, Kinoshita S. Growth factor mRNA and protein in preserved human amniotic membrane. Curr Eye Res. 2000;20:173–7.

    Article  CAS  Google Scholar 

  36. Fetterolf DE, Snyder RJ. Scientific and clinical support for the use of dehydrated amniotic membrane in wound management. Wounds. 2012;24:299–307.

    Google Scholar 

  37. Otsuka T, Kan HM, Laurencin CT. Regenerative engineering approaches to scar-free skin regeneration. Regen Eng Transl Med. 2022;8:225–47. https://doi.org/10.1007/s40883-021-00229-8.

    Article  CAS  Google Scholar 

  38. King AE, Paltoo A, Kelly RW, Sallenave JM, Bocking AD, Challis JRG. Expression of natural antimicrobials by human placenta and fetal membranes. Placenta. 2007;28:161–9. https://doi.org/10.1016/j.placenta.2006.01.006.

    Article  CAS  Google Scholar 

  39. Buhimschi IA, Jabr M, Buhimschi CS, Petkova AP, Weiner CP, Saed GM. The novel antimicrobial peptide β3-defensin is produced by the amnion: a possible role of the fetal membranes in innate immunity of the amniotic cavity. Am J Obstet Gynecol. 2004;191:1678–87. https://doi.org/10.1016/j.ajog.2004.03.081.

    Article  CAS  Google Scholar 

  40. Tehrani FA, Modaresifar K, Azizian S, Niknejad H. Induction of antimicrobial peptides secretion by IL-1β enhances human amniotic membrane for regenerative medicine. Sci Rep. 2017;7:17022. https://doi.org/10.1038/s41598-017-17210-7.

    Article  CAS  Google Scholar 

  41. Kim HS, Cho JH, Park HW, Yoon H, Kim MS, Kim SC. Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol. 2002;168:2356–64. https://doi.org/10.4049/jimmunol.168.5.2356.

    Article  CAS  Google Scholar 

  42. Zare-Bidaki M, Sadrinia S, Erfani S, Afkar E, Ghanbarzade N. Antimicrobial properties of amniotic and chorionic membranes: a comparative study of two human fetal sacs. J Reprod Infertil. 2017;18:218–24.

    Google Scholar 

  43. Niknejad H, Yazdanpanah G, Ahmadiani A. Induction of apoptosis, stimulation of cell-cycle arrest and inhibition of angiogenesis make human amnion-derived cells promising sources for cell therapy of cancer. Cell Tissue Res. 2016;363:599–608. https://doi.org/10.1007/s00441-016-2364-3.

    Article  CAS  Google Scholar 

  44. Modaresifar K, Azizian S, Zolghadr M, Moravvej H, Ahmadiani A, Niknejad H. The effect of cryopreservation on anti-cancer activity of human amniotic membrane. Cryobiol. 2017;74:61–7. https://doi.org/10.1016/j.cryobiol.2016.12.001.

    Article  CAS  Google Scholar 

  45. Niknejad H, Khayat-Khoei M, Peirovi H, Abolghasemi H. Human amniotic epithelial cells induce apoptosis of cancer cells: a new anti-tumor therapeutic strategy. Cytotherapy. 2014;16:33–40. https://doi.org/10.1016/j.jcyt.2013.07.005.

    Article  CAS  Google Scholar 

  46. Kang NH, Hwang KA, Kim SU, Kim YB, Hyun SH, Jeung EB, et al. Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid-derived stem cells. Cancer Gene Ther. 2012;19:517–22. https://doi.org/10.1038/cgt.2012.30.

    Article  CAS  Google Scholar 

  47. Mamede AC, Guerra S, Laranjo M, Carvalho MJ, Oliveira RC, Gonçalves AC, et al. Selective cytotoxicity and cell death induced by human amniotic membrane in hepatocellular carcinoma. Med Oncol. 2015;32:257. https://doi.org/10.1007/s12032-015-0702-z.

    Article  CAS  Google Scholar 

  48. Magatti M, De Munari S, Vertua E, Parolini O. Amniotic membrane-derived cells inhibit proliferation of cancer cell lines by inducing cell cycle arrest. J Cell Mol Med. 2012;16:2208–18. https://doi.org/10.1111/j.1582-4934.2012.01531.x.

    Article  CAS  Google Scholar 

  49. Niknejad H, Paeini-Vayghan G, Tehrani FA, Khayat-Khoei M, Peirovi H. Side dependent effects of the human amnion on angiogenesis. Placenta. 2013;34:340–5. https://doi.org/10.1016/j.placenta.2013.02.001.

    Article  CAS  Google Scholar 

  50. Yazdanpanah G, Paeini-Vayghan G, Asadi S, Niknejad H. The effects of cryopreservation on angiogenesis modulation activity of human amniotic membrane. Cryobiol. 2015;71:413–8. https://doi.org/10.1016/j.cryobiol.2015.09.008.

    Article  CAS  Google Scholar 

  51. Yadav L, Puri N, Rastogi V, Satpute P, Sharma V. Tumour angiogenesis and angiogenic inhibitors: a review. J Clin Diagnostic Res. 2015;9:XE01–5. https://doi.org/10.7860/JCDR/2015/12016.6135.

    Article  CAS  Google Scholar 

  52. Bhattacharjee M, Escobar Ivirico JL, Kan H-M, Shah S, Otsuka T, Bordett R, et al. Injectable amnion hydrogel-mediated delivery of adipose-derived stem cells for osteoarthritis treatment. Proc Natl Acad Sci U S A. 2022;119:e2120968119. https://doi.org/10.1073/pnas.2120968119.

    Article  CAS  Google Scholar 

  53. Awad M, Kurlander DE, Kotha VS, Malone K, Davidson EH, Kumar AR. Amniotic membrane scaffolds support organized muscle regeneration in a murine volumetric muscle defect model. Plast Reconstr Surg-Glob Open. 2022;10:E4499. https://doi.org/10.1097/GOX.0000000000004499.

    Article  Google Scholar 

  54. Samandari M, Tamizifar A, Hosseinian M, Adibi S, Razavi S. Amniotic membrane as an accelator in mandibular bone defects repair. Dent Res J (Isfahan). 2023;20:13. https://doi.org/10.4103/1735-3327.367912.

    Article  Google Scholar 

  55. Woodall BM, Elena N, Gamboa JT, Shin EC, Pathare N, McGahan PJ, et al. Anterior cruciate ligament reconstruction with amnion biological augmentation. Arthrosc Tech. 2018;7:e355–60. https://doi.org/10.1016/j.eats.2017.10.002.

    Article  Google Scholar 

  56. Oyen ML, Cook RF, Calvin SE. Mechanical failure of human fetal membrane tissues. J Mater Sci Mater Med. 2004;15:651–8. https://doi.org/10.1023/B:JMSM.0000030205.62668.90.

    Article  CAS  Google Scholar 

  57. George AK, Dalvi YB, Balram B, KJ N, Anil S. Amnion and chorion membranes for root coverage procedures: an in vitro evaluation of its physical characteristics. Periodontics Prosthodont. 2018:04. https://doi.org/10.21767/2471-3082.100043.

  58. McQuilling JP, Vines JB, Kimmerling KA, Mowry KC. Proteomic comparison of amnion and chorion and evaluation of the effects of processing on placental membranes. Wounds a Compend Clin Res Pract. NIH Public. Access. 2017;29:E38–42.

    Google Scholar 

  59. Jones B, Li C, Park MS, Lerch A, Jacob V, Johnson N, et al. Comprehensive comparison of amnion stromal cells and chorion stromal cells by RNA-seq. Int J Mol Sci. 2021;22:1–17. https://doi.org/10.3390/ijms22041901.

    Article  CAS  Google Scholar 

  60. Wu M, Zhang R, Zou Q, Chen Y, Zhou M, Li X, et al. Comparison of the biological characteristics of mesenchymal stem cells derived from the human placenta and umbilical cord. Sci Rep. 2018;8:5014. https://doi.org/10.1038/s41598-018-23396-1.

    Article  CAS  Google Scholar 

  61. Namgoong S, Lee H, Lee JS, Jeong SH, Han SK, Dhong ES. Comparative biological effects of human amnion and chorion membrane extracts on human adipose-derived stromal cells. J Craniofac Surg. 2019;30:947–54. https://doi.org/10.1097/SCS.0000000000005393.

    Article  Google Scholar 

  62. Hussey GS, Dziki JL, Badylak SF. Extracellular matrix-based materials for regenerative medicine. Nat Rev Mater. 2018;3:159–73. https://doi.org/10.1038/s41578-018-0023-x.

    Article  CAS  Google Scholar 

  63. von Versen-Hoeynck F, Steinfeld AP, Becker J, Hermel M, Rath W, Hesselbarth U. Sterilization and preservation influence the biophysical properties of human amnion grafts. Biologicals. 2008;36:248–55. https://doi.org/10.1016/j.biologicals.2008.02.001.

    Article  CAS  Google Scholar 

  64. Wang B, Qinglai T, Yang Q, Li M, Zeng S, Yang X, et al. Functional acellular matrix for tissue repair. Mater Today Bio. 2023;18:100530. https://doi.org/10.1016/j.mtbio.2022.100530.

    Article  CAS  Google Scholar 

  65. Milan PB, Amini N, Joghataei MT, Ebrahimi L, Amoupour M, Sarveazad A, et al. Decellularized human amniotic membrane: from animal models to clinical trials. Methods. 2020;171:11–9. https://doi.org/10.1016/j.ymeth.2019.07.018.

    Article  CAS  Google Scholar 

  66. Lakkireddy C, Vishwakarma SK, Raju N, Ahmed SI, Bardia A, Khan MA, et al. Fabrication of decellularized amnion and chorion scaffolds to develop bioengineered cell-laden constructs. Cell Mol Bioeng. 2022;15:137–50. https://doi.org/10.1007/s12195-021-00707-7.

    Article  CAS  Google Scholar 

  67. Ashouri S, Hosseini SA, Hoseini SJ, Tara F, Ebrahimzadeh-Bideskan A, Webster TJ, et al. Decellularization of human amniotic membrane using detergent-free methods: possibilities in tissue engineering. Tissue Cell. 2022;76:101818. https://doi.org/10.1016/j.tice.2022.101818.

    Article  CAS  Google Scholar 

  68. Liu C, Pei M, Li Q, Zhang Y. Decellularized extracellular matrix mediates tissue construction and regeneration. Front Med. 2022;16:56–82. https://doi.org/10.1007/s11684-021-0900-3.

    Article  CAS  Google Scholar 

  69. Ryzhuk V, Zeng XX, Wang X, Melnychuk V, Lankford L, Farmer D, et al. Human amnion extracellular matrix derived bioactive hydrogel for cell delivery and tissue engineering. Mater Sci Eng C. 2018;85:191–202. https://doi.org/10.1016/j.msec.2017.12.026.

    Article  CAS  Google Scholar 

  70. Tang K, Wu J, Xiong Z, Ji Y, Sun T, Guo X. Human acellular amniotic membrane: a potential osteoinductive biomaterial for bone regeneration. J Biomater Appl. 2018;32:754–64. https://doi.org/10.1177/0885328217739753.

    Article  CAS  Google Scholar 

  71. Liu C, Yu K, Bai J, Tian D, Liu G. Experimental study of tendon sheath repair via decellularized amnion to prevent tendon adhesion. PLoS One. 2018;13:e0205811. https://doi.org/10.1371/journal.pone.0205811.

    Article  CAS  Google Scholar 

  72. Li W, Ma G, Brazile B, Li N, Dai W, Butler JR, et al. Investigating the potential of amnion-based scaffolds as a barrier membrane for guided bone regeneration. Langmuir. 2015;31:8642–53. https://doi.org/10.1021/acs.langmuir.5b02362.

    Article  CAS  Google Scholar 

  73. Semyari H, Rajipour M, Sabetkish S, Sabetkish N, Abbas FM, Kajbafzadeh AM. Evaluating the bone regeneration in calvarial defect using osteoblasts differentiated from adipose-derived mesenchymal stem cells on three different scaffolds: an animal study. Cell Tissue Bank. 2016;17:69–83. https://doi.org/10.1007/s10561-015-9518-5.

    Article  CAS  Google Scholar 

  74. Salah RA, Mohamed IK, El-Badri N. Development of decellularized amniotic membrane as a bioscaffold for bone marrow-derived mesenchymal stem cells: ultrastructural study. J Mol Histol. 2018;49:289–301. https://doi.org/10.1007/s10735-018-9768-1.

    Article  CAS  Google Scholar 

  75. Bhattacharjee M, Ivirico JLE, Kan HM, Bordett R, Pandey R, Otsuka T, et al. Preparation and characterization of amnion hydrogel and its synergistic effect with adipose derived stem cells towards IL1β activated chondrocytes. Sci Rep. 2020;10:18751. https://doi.org/10.1038/s41598-020-75921-w.

    Article  CAS  Google Scholar 

  76. Poole AR, Kojima T, Yasuda T, Mwale F, Kobayashi M, Laverty S. Composition and structure of articular cartilage: a template for tissue repair. Clin Orthop Relat Res. 2001;391:S26.

    Article  Google Scholar 

  77. Aigner T, Söder S, Gebhard PM, McAlinden A, Haag J. Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis - structure, chaos and senescence. Nat Clin Pract Rheumatol. 2007;3:391–9. https://doi.org/10.1038/ncprheum0534.

    Article  CAS  Google Scholar 

  78. Eyre DR, Weis MA, Wu JJ. Articular cartilage collagen: an irreplaceable framework? Eur Cells Mater. 2006;12:57–63. https://doi.org/10.22203/eCM.v012a07.

    Article  CAS  Google Scholar 

  79. Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998;41:778–99. https://doi.org/10.1002/1529-0131(199805)41:5<778::AID-ART4>3.0.CO;2-V.

    Article  CAS  Google Scholar 

  80. Quintana JM, Arostegui I, Escobar A, Azkarate J, Goenaga JI, Lafuente I. Prevalence of knee and hip osteoarthritis and the appropriateness of joint replacement in an older population. Arch Intern Med. 2008;168:1576–84. https://doi.org/10.1001/archinte.168.14.1576.

    Article  Google Scholar 

  81. Krishnamurithy G, Shilpa PN, Ahmad RE, Sulaiman S, Ng CLL, Kamarul T. Human amniotic membrane as a chondrocyte carrier vehicle/substrate: in vitro study. J Biomed Mater Res - Part A. 2011;99:500–6. https://doi.org/10.1002/jbm.a.33184.

    Article  CAS  Google Scholar 

  82. Boo L, Sofiah S, Selvaratnam L, Tai C, B P-M, Kamarul T. A preliminary study of human amniotic membrane as a potential chondrocyte carrier. Malaysian Orthop J. 2009;3:16–23.

    Article  Google Scholar 

  83. Cheng ZJ, So RP, Byung HC, Lee KY, Choong KK, Min BH. Human amniotic membrane as a delivery matrix for articular cartilage repair. Tissue Eng. 2007;13:693–702. https://doi.org/10.1089/ten.2006.0184.

    Article  Google Scholar 

  84. Garcia D, Longo U, Vaquero J, Forriol F, Loppini M, Khan W, et al. Amniotic membrane transplant for articular cartilage repair: an experimental study in sheep. Curr Stem Cell Res Ther. 2014;10:77–83. https://doi.org/10.2174/1574888x09666140710120012.

    Article  CAS  Google Scholar 

  85. Willett NJ, Thote T, Lin ASP, Moran S, Raji Y, Sridaran S, et al. Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development. Arthritis Res Ther. 2014;16:R47. https://doi.org/10.1186/ar4476.

    Article  Google Scholar 

  86. Marino-Martínez IA, Martínez-Castro AG, Peña-Martínez VM, Acosta-Olivo CA, Vílchez-Cavazos F, Guzmán-López A, et al. Human amniotic membrane intra-articular injection prevents cartilage damage in an osteoarthritis model. Exp Ther Med. 2018;17:11–6. https://doi.org/10.3892/etm.2018.6924.

    Article  CAS  Google Scholar 

  87. Kimmerling KA, Gomoll AH, Farr J, Mowry KC. Amniotic suspension allograft modulates inflammation in a rat pain model of osteoarthritis. J Orthop Res. 2020;38:1141–9. https://doi.org/10.1002/jor.24559.

    Article  CAS  Google Scholar 

  88. Lin ASP, Reece DS, Thote T, Sridaran S, Stevens HY, Willett NJ, et al. Intra-articular delivery of micronized dehydrated human amnion/chorion membrane reduces degenerative changes after onset of post-traumatic osteoarthritis. Front Bioeng. Biotechnol. 2023:11. https://doi.org/10.3389/fbioe.2023.1224141.

  89. Cao L, Tong Y, Wang X, Zhang Q, Qi Y, Zhou C, et al. Effect of amniotic membrane/collagen-based scaffolds on the chondrogenic differentiation of adipose-derived stem cells and cartilage repair. Front Cell. Dev Biol. 2021:9. https://doi.org/10.3389/fcell.2021.647166.

  90. Topoluk N, Hawkins R, Tokish J, Mercuri J. Amniotic mesenchymal stromal cells exhibit preferential osteogenic and chondrogenic differentiation and enhanced matrix production compared with adipose mesenchymal stromal cells. Am J Sports Med. 2017;45:2637–46. https://doi.org/10.1177/0363546517706138.

    Article  Google Scholar 

  91. Wei JP, Nawata M, Wakitani S, Kametani K, Ota M, Toda A, et al. Human amniotic mesenchymal cells differentiate into chondrocytes. Cloning Stem Cells. 2009;11:19–25. https://doi.org/10.1089/clo.2008.0027.

    Article  CAS  Google Scholar 

  92. Vines JB, Aliprantis AO, Gomoll AH, Farr J. Cryopreserved amniotic suspension for the treatment of knee osteoarthritis. J Knee Surg. 2016;29:443–50. https://doi.org/10.1055/s-0035-1569481.

    Article  Google Scholar 

  93. Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC. A Randomized controlled single-blind study demonstrating superiority of amniotic suspension allograft injection over hyaluronic acid and saline control for modification of knee osteoarthritis symptoms. J Knee Surg. 2019;32:1143–54. https://doi.org/10.1055/s-0039-1696672.

    Article  Google Scholar 

  94. Gomoll AH, Farr J, Cole BJ, Flanigan DC, Lattermann C, Mandelbaum BR, et al. Safety and efficacy of an amniotic suspension allograft injection over 12 months in a single-blinded, randomized controlled trial for symptomatic osteoarthritis of the knee. Arthrosc-J Arthrosc Relat Surg. 2021;37:2246–57. https://doi.org/10.1016/j.arthro.2021.02.044.

    Article  Google Scholar 

  95. Tabet SK, Kimmerling KA, Hale GJ, Munson NR, Mowry KC. Hypothermically stored amniotic membrane for the treatment of cartilage lesions: a single-arm prospective study with 2-year follow-up. Cartilage. 2022;13:194760352110722. https://doi.org/10.1177/19476035211072213.

    Article  CAS  Google Scholar 

  96. Chen YJ, Chung MC, Jane Yao CC, Huang CH, Chang HH, Jeng JH, et al. The effects of acellular amniotic membrane matrix on osteogenic differentiation and ERK1/2 signaling in human dental apical papilla cells. Biomater. 2012;33:455–63. https://doi.org/10.1016/j.biomaterials.2011.09.065.

    Article  CAS  Google Scholar 

  97. Koushaei S, Samandari MH, Razavi SM, Khoshzaban A, Adibi S, Varedi P. Histological comparison of new bone formation using amnion membrane graft versus resorbable collagen membrane: an animal study. J Oral Implantol. 2018;44:335–40. https://doi.org/10.1563/aaid-joi-D-16-00120.

    Article  Google Scholar 

  98. Hankenson KD, Dishowitz M, Gray C, Schenker M. Angiogenesis in bone regeneration. Injury. 2011;42:556–61. https://doi.org/10.1016/j.injury.2011.03.035.

    Article  Google Scholar 

  99. Niknejad H, Yazdanpanah G. Opposing effect of amniotic membrane on angiogenesis originating from amniotic epithelial cells. J Med Hypotheses Ideas. 2014;8:39–41. https://doi.org/10.1016/j.jmhi.2013.08.002.

    Article  CAS  Google Scholar 

  100. Ramuta TŽ, Kreft ME. Human amniotic membrane and amniotic membrane–derived cells: how far are we from their use in regenerative and reconstructive urology? Cell Transplant. 2018;27:77–92. https://doi.org/10.1177/0963689717725528.

    Article  Google Scholar 

  101. Fénelon M, Chassande O, Kalisky J, Gindraux F, Brun S, Bareille R, et al. Human amniotic membrane for guided bone regeneration of calvarial defects in mice. J Mater Sci Mater Med. 2018;29:78. https://doi.org/10.1007/s10856-018-6086-9.

    Article  CAS  Google Scholar 

  102. Barboni B, Mangano C, Valbonetti L, Marruchella G, Berardinelli P, Martelli A, et al. Synthetic bone substitute engineered with amniotic epithelial cells enhances bone regeneration after maxillary sinus augmentation. PLoS One. 2013;8:e63256. https://doi.org/10.1371/journal.pone.0063256.

    Article  CAS  Google Scholar 

  103. Lindenmair A, Wolbank S, Stadler G, Meinl A, Peterbauer-Scherb A, Eibl J, et al. Osteogenic differentiation of intact human amniotic membrane. Biomater. 2010;31:8659–65. https://doi.org/10.1016/j.biomaterials.2010.07.090.

    Article  CAS  Google Scholar 

  104. Rodrigues MT, Lee BK, Lee SJ, Gomes ME, Reis RL, Atala A, et al. The effect of differentiation stage of amniotic fluid stem cells on bone regeneration. Biomater. 2012;33:6069–78. https://doi.org/10.1016/j.biomaterials.2012.05.016.

    Article  CAS  Google Scholar 

  105. Kolliopoulos V, Dewey MJ, Polanek M, Xu H, Harley BAC. Amnion and chorion matrix maintain hMSC osteogenic response and enhance immunomodulatory and angiogenic potential in a mineralized collagen scaffold. Front Bioeng. Biotechnol. 2022:10. https://doi.org/10.3389/fbioe.2022.1034701.

  106. Li Y, Liu Z, Jin Y, Zhu X, Wang S, Yang J, et al. Differentiation of human amniotic mesenchymal stem cells into human anterior cruciate ligament fibroblast cells by in vitro coculture. Biomed Res Int. 2017;2017:e7360354. https://doi.org/10.1155/2017/7360354.

    Article  CAS  Google Scholar 

  107. Lange-Consiglio A, Rossi D, Tassan S, Perego R, Cremonesi F, Parolini O. Conditioned medium from horse amniotic membrane-derived multipotent progenitor cells: immunomodulatory activity in vitro and first clinical application in tendon and ligament injuries in vivo. Stem Cells Dev. 2013;22:3015–24. https://doi.org/10.1089/scd.2013.0214.

    Article  CAS  Google Scholar 

  108. Lange-Consiglio A, Tassan S, Corradetti B, Meucci A, Perego R, Bizzaro D, et al. Investigating the efficacy of amnion-derived compared with bone marrow-derived mesenchymal stromal cells in equine tendon and ligament injuries. Cytotherapy. 2013;15:1011–20. https://doi.org/10.1016/j.jcyt.2013.03.002.

    Article  CAS  Google Scholar 

  109. Levengood A, G. Arthroscopic-assisted anterior cruciate ligament reconstruction using hamstring autograft augmented with a dehydrated human amnion/chorion membrane allograft: a retrospective case report. Orthop Muscular Syst. 2016:05. https://doi.org/10.4172/2161-0533.1000213.

  110. James R, Kesturu G, Balian G, Chhabra AB. Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. J Hand Surg Am. 2008;33:102–12. https://doi.org/10.1016/j.jhsa.2007.09.007.

    Article  Google Scholar 

  111. Kueckelhaus M, Philip J, Kamel RA, Canseco JA, Hackl F, Kiwanuka E, et al. Sustained release of amnion-derived cellular cytokine solution facilitates achilles tendon healing in rats. Eplasty. 2014;14:e29.

    Google Scholar 

  112. Nicodemo M de C, Das Neves LR, Aguiar JC, Brito F de S, Ferreira I, LB SA, et al. Amniotic membrane as an option for treatment of acute achilles tendon injury in rats. Acta Cir Bras. 2017;32:125–39. https://doi.org/10.1590/s0102-865020170205.

    Article  Google Scholar 

  113. Demirkan F, Colakoglu N, Herek O, Erkula G. The use of amniotic membrane in flexor tendon repair: an experimental model. Arch Orthop Trauma Surg. 2002;122:396–9. https://doi.org/10.1007/s00402-002-0418-3.

    Article  Google Scholar 

  114. Muttini A, Mattioli M, Petrizzi L, Varasano V, Sciarrini C, Russo V, et al. Experimental study on allografts of amniotic epithelial cells in calcaneal tendon lesions of sheep. Vet Res Commun. 2010;34:117–20. https://doi.org/10.1007/s11259-010-9396-z.

    Article  Google Scholar 

  115. Barboni B, Russo V, Curini V, Mauro A, Martelli A, Muttini A, et al. Achilles tendon regeneration can be improved by amniotic epithelial cell allotransplantation. Cell Transplant. 2012;21:2377–95. https://doi.org/10.3727/096368912X638892.

    Article  CAS  Google Scholar 

  116. Philip J, Hackl F, Canseco JA, Kamel RA, Kiwanuka E, Diaz-Siso JR, et al. Amnion-derived multipotent progenitor cells improve achilles tendon repair in rats. Eplasty. 2013;13:e31.

    Google Scholar 

  117. Anderson LE, Pearson JJ, Brimeyer AL, Temenoff JS. Injection of micronized human amnion/chorion membrane results in increased early supraspinatus muscle regeneration in a chronic model of rotator cuff tear. Ann Biomed Eng. 2021;49:3698–710. https://doi.org/10.1007/s10439-021-02880-2.

    Article  Google Scholar 

  118. Girolamo L de, Ambra LFM, Orfei CP, McQuilling JP, Kimmerling KA, Mowry KC, et al. Treatment with human amniotic suspension allograft improves tendon healing in a rat model of collagenase-induced tendinopathy. Cells. 2019;8:1411 https://doi.org/10.3390/cells8111411

  119. DeMill SL, Granata JD, McAlister JE, Berlet GC, Hyer CF. Safety analysis of cryopreserved amniotic membrane/umbilical cord tissue in foot and ankle surgery: a consecutive case series of 124 patients. Surg Technol Int. 2014;25:257–61.

    Google Scholar 

  120. Zelen CM, Poka A, Andrews J. Prospective, randomized, blinded, comparative study of injectable micronized dehydrated amniotic/chorionic membrane allograft for plantar fasciitis - a feasibility study. Foot Ankle Int. 2013;34:1332–9. https://doi.org/10.1177/1071100713502179.

    Article  Google Scholar 

  121. Hanselman AE, Tidwell JE, Santrock RD. Cryopreserved human amniotic membrane injection for plantar fasciitis: a randomized, controlled, double-blind pilot study. Foot Ankle Int. 2015;36:151–8. https://doi.org/10.1177/1071100714552824.

    Article  Google Scholar 

  122. Lullove E. A flowable placental tissue matrix allograft in lower extremity injuries: a pilot study. Cureus. 2015;7:e275. https://doi.org/10.7759/cureus.275.

    Article  Google Scholar 

  123. Werber B. Amniotic tissues for the treatment of chronic plantar fasciosis and achilles tendinosis. J Sports Med. 2015;2015:219896. https://doi.org/10.1155/2015/219896.

    Article  Google Scholar 

  124. Gellhorn AC, Han A. The use of dehydrated human amnion/chorion membrane allograft injection for the treatment of tendinopathy or arthritis: a case series involving 40 patients. PM R. 2017;9:1236–43. https://doi.org/10.1016/j.pmrj.2017.04.011.

    Article  Google Scholar 

  125. López-Valladares MJ, Teresa Rodríguez-Ares M, Touriño R, Gude F, Teresa Silva M, Couceiro J. Donor age and gestational age influence on growth factor levels in human amniotic membrane. Acta Ophthalmol. 2010;88:e211–6. https://doi.org/10.1111/j.1755-3768.2010.01908.x.

    Article  Google Scholar 

  126. Akle CA, Welsh KI, Adinolfi M, Leibowitz S, Mccoll I. Immunogenicity of human amniotic epithelial cells after transplantation into volunteers. Lancet. 1981;318:1003–5. https://doi.org/10.1016/S0140-6736(81)91212-5.

    Article  Google Scholar 

  127. Okabe M, Kitagawa K, Yoshida T, Suzuki T, Waki H, Koike C, et al. Hyperdry human amniotic membrane is useful material for tissue engineering: physical, morphological properties, and safety as the new biological material. J Biomed Mater Res-Part A. 2014;102:862–70. https://doi.org/10.1002/jbm.a.34753.

    Article  CAS  Google Scholar 

  128. Kitagawa K, Yanagisawa S, Watanabe K, Yunoki T, Hayashi A, Okabe M, et al. A hyperdry amniotic membrane patch using a tissue adhesive for corneal perforations and bleb leaks. Am J Ophthalmol. 2009;148:383–389.e1. https://doi.org/10.1016/j.ajo.2009.03.030.

    Article  Google Scholar 

  129. Kitagawa K, Okabe M, Yanagisawa S, Zhang XY, Nikaido T, Hayashi A. Use of a hyperdried cross-linked amniotic membrane as initial therapy for corneal perforations. Jpn J Ophthalmol. 2011;55:16–21. https://doi.org/10.1007/s10384-010-0903-0.

    Article  CAS  Google Scholar 

  130. Okabe M, Kitagawa K, Yoshida T, Koike C, Katsumoto T, Fujihara E, et al. Application of 2-octyl-cyanoacrylate for corneal perforation and glaucoma filtering bleb leak. Clin Ophthalmol. 2013;7:649–53. https://doi.org/10.2147/OPTH.S43106.

    Article  CAS  Google Scholar 

  131. Tomita T, Hayashi N, Okabe M, Yoshida T, Hamada H, Endo S, et al. New dried human amniotic membrane is useful as a substitute for dural repair after skull base surgery. J Neurol Surgery Part B Skull Base. 2012;73:302–7. https://doi.org/10.1055/s-0032-1321506.

    Article  Google Scholar 

  132. Arai N, Tsuno H, Okabe M, Yoshida T, Koike C, Noguchi M, et al. Clinical application of a hyperdry amniotic membrane on surgical defects of the oral mucosa. J Oral Maxillofac Surg. 2012;70:2221–8. https://doi.org/10.1016/j.joms.2011.09.033.

    Article  Google Scholar 

  133. Lai JY, Ma DHK. Glutaraldehyde cross-linking of amniotic membranes affects their nanofibrous structures and limbal epithelial cell culture characteristics. Int J Nanomed. 2013;8:4157–68. https://doi.org/10.2147/IJN.S52731.

    Article  CAS  Google Scholar 

  134. Barski D, Gerullis H, Ecke T, Yang J, Varga G, Boros M, et al. Bladder reconstruction with human amniotic membrane in a xenograft rat model: a preclinical study. Int J Med Sci. 2017;14:310–8. https://doi.org/10.7150/ijms.18127.

    Article  Google Scholar 

  135. Dadkhah Tehrani F, Firouzeh A, Shabani I, Shabani A. A review on modifications of amniotic membrane for biomedical applications. Front Bioeng Biotechnol. 2021;8:606982. https://doi.org/10.3389/fbioe.2020.606982.

    Article  Google Scholar 

  136. Niknejad H, Deihim T, Peirovi H, Abolghasemi H. Serum-free cryopreservation of human amniotic epithelial cells before and after isolation from their natural scaffold. Cryobiol. 2013;67:56–63. https://doi.org/10.1016/j.cryobiol.2013.05.001.

    Article  CAS  Google Scholar 

  137. Kubo M, Sonoda Y, Muramatsu R, Usui M. Immunogenicity of human amniotic membrane in experimental xenotransplantation. Investig Ophthalmol Vis Sci. 2001;42:1539–46.

    CAS  Google Scholar 

  138. K Tabet S, Clark AL, Chapman EB, Thal D. The use of hypothermically stored amniotic membrane for cartilage repair: a sheep study. Stem Cell Discov. 2015;05:62–71. https://doi.org/10.4236/scd.2015.54007.

    Article  CAS  Google Scholar 

  139. Raines AL, Shih MS, Chua L, Su CW, Tseng SCG, O’Connell J. Efficacy of particulate amniotic membrane and umbilical cord tissues in attenuating cartilage destruction in an osteoarthritis model. Tissue Eng Part A. 2017;23:12–9. https://doi.org/10.1089/ten.TEA.2016.0088.

    Article  CAS  Google Scholar 

  140. Muttini A, Valbonetti L, Abate M, Colosimo A, Curini V, Mauro A, et al. Ovine amniotic epithelial cells: in vitro characterization and transplantation into equine superficial digital flexor tendon spontaneous defects. Res Vet Sci. 2013;94:158–69. https://doi.org/10.1016/j.rvsc.2012.07.028.

    Article  CAS  Google Scholar 

  141. Anderson JJ, Swayzee Z. The use of human amniotic allograft on osteochondritis dissecans of the talar dome: a comparison with and without allografts in arthroscopically treated ankles. Surg Sci. 2015;06:412–7. https://doi.org/10.4236/ss.2015.69059.

    Article  Google Scholar 

  142. Liu C, Bai J, Yu K, Liu G, Tian S, Tian D. Biological amnion prevents flexor tendon adhesion in zone II: a controlled, multicentre clinical trial. Biomed Res Int. 2019;2019:e2354325. https://doi.org/10.1155/2019/2354325.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This review is funded in part by the National Institute of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) award number AR079114-01 for Godwin K. Dzidotor. Additional support from the Biomedical Trust Fund from the State of Connecticut is gratefully acknowledged. Biorender.com was used for the illustration.

Author information

Authors and Affiliations

Authors

Contributions

The manuscript was conceptualized and written through the contributions of all authors. All authors have approved the final version of the manuscript.

Corresponding author

Correspondence to Cato T. Laurencin.

Ethics declarations

Competing Interests

L.S.N. has competing financial interest with Soft Tissue Regeneration/Biorez/Conmed. C.T.L. has the following competing financial interests: Mimedx, Alkermes Company, Biobind, Soft Tissue Regeneration/Biorez/Conmed, and Healing Orthopaedic Technologies-Bone. C.T.L. serves on the board of Mimedx which makes amnion products. All other authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Maumita Bhattacharjee and Takayoshi Otsuka are co-first authors.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhattacharjee, M., Otsuka, T., Dzidotor, G.K. et al. Amnion-Based Biomaterials for Musculoskeletal Regenerative Engineering. Regen. Eng. Transl. Med. (2023). https://doi.org/10.1007/s40883-023-00321-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40883-023-00321-1

Keywords

Navigation