Skip to main content

Advertisement

SpringerLink
Log in

Recent Advancements in Engineered Biomaterials for the Regeneration of Female Reproductive Organs

  • Review
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Various gynecologic diseases and chemoradiation or surgery for the management of gynecologic malignancies may damage the uterus and ovaries, leading to clinical problems such as infertility or early menopause. Embryo or oocyte cryopreservation—the standard method for fertility preservation—is not a feasible option for patients who require urgent treatment because the procedure requires ovarian stimulation for at least several days. Hormone replacement therapy (HRT) for patients diagnosed with premature menopause is contraindicated for patients with estrogen-dependent tumors or a history of thrombosis. Furthermore, these methods cannot restore the function of the uterus and ovaries. Although autologous transplantation of cryopreserved ovarian tissue is being attempted, it may re-introduce malignant cells after cancer treatment. With the recent development in regenerative medicine, research on engineered biomaterials for the restoration of female reproductive organs is being actively conducted. The use of engineered biomaterials is a promising option in the field of reproductive medicine because it can overcome the limitations of current therapies. Here, we review the ideal properties of biomaterials for reproductive tissue engineering and the recent advancements in engineered biomaterials for the regeneration of female reproductive organs.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

Not applicable.

References

  1. Group, S.G.O.C.P.E.C.W, et al. Endometrial cancer: a review and current management strategies: part II. Gynecol Oncol. 2014;134(2):393–402.

    Article  Google Scholar 

  2. Vassilakopoulou M, Boostandoost E, Papaxoinis G, de la Motte Rouge T, Khayat D, Psyrri A. Anticancer treatment and fertility: effect of therapeutic modalities on reproductive system and functions. Crit Rev Oncol Hematol. 2016;97:328–34.

    Article  PubMed  Google Scholar 

  3. Vitale SG, la Rosa VL, Rapisarda AMC, Laganà AS. The importance of fertility preservation counseling in patients with gynecologic cancer. J Reprod Infertil. 2017;18(2):261–3.

    PubMed  PubMed Central  Google Scholar 

  4. Salama M, Mallmann P. Emergency fertility preservation for female patients with cancer: clinical perspectives. Anticancer Res. 2015;35(6):3117–27.

    PubMed  Google Scholar 

  5. Kim H, Kim H, Ku SY. Fertility preservation in pediatric and young adult female cancer patients. Ann Pediatr Endocrinol Metab. 2018;23(2):70–4.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Blagden S, et al. The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours. Br J Cancer. 2002;86(1):26–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Donnez J, Dolmans MM, Diaz C, Pellicer A. Ovarian cortex transplantation: time to move on from experimental studies to open clinical application. Fertil Steril. 2015;104(5):1097–8.

    Article  PubMed  Google Scholar 

  8. Lee S, et al. Comparison between slow freezing and vitrification for human ovarian tissue cryopreservation and xenotransplantation. Int J Mol Sci. 2019:20(13).

  9. De Vos M, Smitz J, Woodruff TK. Fertility preservation in women with cancer. Lancet. 2014;384(9950):1302–10.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Donnez J, Dolmans MM. Fertility preservation in women. N Engl J Med. 2017;377(17):1657–65.

    Article  PubMed  Google Scholar 

  11. Jeruss JS, Woodruff TK. Preservation of fertility in patients with cancer. N Engl J Med. 2009;360(9):902–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Practice, C.o.G. Committee Opinion No. 698: Hormone therapy in primary ovarian insufficiency. Obstet Gynecol. 2017;129(5):e134.

    Article  Google Scholar 

  13. Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. Jama. 2003;289(24):3243–53.

    Article  CAS  PubMed  Google Scholar 

  14. Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, et al. Estrogen Plus Progestin Risk Ven Thromb. Jama. 2004;292(13):1573–80.

    Article  CAS  PubMed  Google Scholar 

  15. Iavazzo C, Gkegkes ID. Possible role of DaVinci Robot in uterine transplantation. J Turk Ger Gynecol Assoc. 2015;16(3):179–80.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Baird DT, Webb R, Campbell BK, Harkness LM, Gosden RG. Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at -196 C. Endocrinology. 1999;140(1):462–71.

    Article  CAS  PubMed  Google Scholar 

  17. David A, Day JR, Cichon AL, Lefferts A, Cascalho M, Shikanov A. Restoring ovarian endocrine function with encapsulated ovarian allograft in immune competent mice. Ann Biomed Eng. 2017;45(7):1685–96.

    Article  PubMed  Google Scholar 

  18. Shikanov A, Zhang Z, Xu M, Smith RM, Rajan A, Woodruff TK, et al. Fibrin encapsulation and vascular endothelial growth factor delivery promotes ovarian graft survival in mice. Tissue Eng Part A. 2011;17(23-24):3095–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Tanaka A, Nakamura H, Tabata Y, Fujimori Y, Kumasawa K, Kimura T. Effect of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogels on frozen-thawed human ovarian tissue in a xenograft model. J Obstet Gynaecol Res. 2018;44(10):1947–55.

    CAS  PubMed  Google Scholar 

  20. Miki F, Maruyama T, Miyazaki K, Takao T, Yoshimasa Y, Katakura S, et al. The orientation of a decellularized uterine scaffold determines the tissue topology and architecture of the regenerated uterus in rats. Biol Reprod. 2019;100(5):1215–27.

    Article  PubMed  Google Scholar 

  21. Miyazaki K, Maruyama T. Partial regeneration and reconstruction of the rat uterus through recellularization of a decellularized uterine matrix. Biomaterials. 2014;35(31):8791–800.

    Article  CAS  PubMed  Google Scholar 

  22. Jiang WC, Cheng YH, Yen MH, Chang Y, Yang VW, Lee OK. Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering. Biomaterials. 2014;35(11):3607–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Santos JM, et al. Immunohistochemical localization of fibroblast growth factor-2 in the sheep ovary and its effects on pre-antral follicle apoptosis and development in vitro. Reprod Domest Anim. 2014;49(3):522–8.

    Article  CAS  PubMed  Google Scholar 

  24. Soleimani R, Heytens E, Oktay K. Enhancement of neoangiogenesis and follicle survival by sphingosine-1-phosphate in human ovarian tissue xenotransplants. PLoS One. 2011;6(4):e19475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kim YJ, Kim YY, Kim DW, Joo JK, Kim H, Ku SY. Profile of MicroRNA expression in endometrial cell during in vitro culture according to progesterone concentration. Tissue Eng Regen Med. 2017;14(5):617–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tamadon A, Park KH, Kim YY, Kang BC, Ku SY. Efficient biomaterials for tissue engineering of female reproductive organs. Tissue Eng Regen Med. 2016;13(5):447–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Black J. Biological performance of materials : fundamentals of biocompatibility. 4th ed. Boca Raton: CRC Taylor & Francis; 2006. p. 497.

    Google Scholar 

  28. Martin JR, Gupta MK, Page JM, Yu F, Davidson JM, Guelcher SA, et al. A porous tissue engineering scaffold selectively degraded by cell-generated reactive oxygen species. Biomaterials. 2014;35(12):3766–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Baah-Dwomoh A, McGuire J, Tan T, de Vita R. Mechanical properties of female reproductive organs and supporting connective tissues: a review of the current state of knowledge. Appl Mech Rev. 2016;68(6):060801.

    Article  Google Scholar 

  30. Chen PY, et al. Structure and mechanical properties of selected biological materials. J Mech Behav Biomed Mater. 2008;1(3):208–26.

    Article  PubMed  Google Scholar 

  31. Hassanpour A, Talaei-Khozani T, Kargar-Abarghouei E, Razban V, Vojdani Z. Decellularized human ovarian scaffold based on a sodium lauryl ester sulfate (SLES)-treated protocol, as a natural three-dimensional scaffold for construction of bioengineered ovaries. Stem Cell Res Ther. 2018;9:252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ku SY, Choi YM, Suh CS, Kim SH, Kim JG, Moon SY, et al. Effect of gonadotropins on human endometrial stromal cell proliferation in vitro. Arch Gynecol Obstet. 2002;266(4):223–8.

    Article  CAS  PubMed  Google Scholar 

  33. Alshaikh AB, Padma AM, Dehlin M, Akouri R, Song MJ, Brännström M, et al. Decellularization of the mouse ovary: comparison of different scaffold generation protocols for future ovarian bioengineering. J Ovarian Res. 2019;12(1):58.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wood CD, Vijayvergia M, Miller FH, Carroll T, Fasanati C, Shea LD, et al. Multi-modal magnetic resonance elastography for noninvasive assessment of ovarian tissue rigidity in vivo. Acta Biomater. 2015;13:295–300.

    Article  PubMed  Google Scholar 

  35. Engelmayr GC Jr, Cheng M, Bettinger CJ, Borenstein JT, Langer R, Freed LE. Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nat Mater. 2008;7(12):1003–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Woodruff TK, Shea LD. A new hypothesis regarding ovarian follicle development: ovarian rigidity as a regulator of selection and health. J Assist Reprod Genet. 2011;28(1):3–6.

    Article  PubMed  Google Scholar 

  37. Zhang Y, An D, Pardo Y, Chiu A, Song W, Liu Q, et al. High-water-content and resilient PEG-containing hydrogels with low fibrotic response. Acta biomaterialia. 2017;53:100–8.

    Article  CAS  PubMed  Google Scholar 

  38. Lynn AD, Kyriakides TR, Bryant SJ. Characterization of the in vitro macrophage response and in vivo host response to poly(ethylene glycol)-based hydrogels. J Biomed Mater Res A. 2010;93(3):941–53.

    PubMed  Google Scholar 

  39. Hillel AT, et al. Photoactivated composite biomaterial for soft tissue restoration in rodents and in humans. Sci Transl Med. 2011;3(93):93ra67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wang DA, Varghese S, Sharma B, Strehin I, Fermanian S, Gorham J, et al. Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration. Nat Mater. 2007;6(5):385–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Metters AT, Anseth KS, Bowman CN. Fundamental studies of a novel, biodegradable PEG-b-PLA hydrogel. Polymer. 2000;41(11):3993–4004.

    Article  CAS  Google Scholar 

  42. Chiu YC, Kocagöz S, Larson JC, Brey EM. Evaluation of physical and mechanical properties of porous poly (ethylene glycol)-co-(L-lactic acid) hydrogels during degradation. PLoS ONE. 2013;8(4):e60728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Artzi N, Oliva N, Puron C, Shitreet S, Artzi S, bon Ramos A, et al. In vivo and in vitro tracking of erosion in biodegradable materials using non-invasive fluorescence imaging (vol 10, pg 704, 2011). Nat Mater. 2011;10(11):896.

    Article  CAS  Google Scholar 

  44. Lee BK, Yun Y, Park K. PLA micro- and nano-particles. Adv Drug Deliv Rev. 2016;107:176–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Meng CX, Andersson KL, Bentin-Ley U, Gemzell-Danielsson K, Lalitkumar PGL. Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model. Fertil Steril. 2009;91(1):256–64.

    Article  CAS  PubMed  Google Scholar 

  46. Zhou H, Malik MA, Arab A, Hill MT, Shikanov A. Hydrogel based 3-dimensional (3D) system for toxicity and high-throughput (HTP) analysis for cultured murine ovarian follicles. PLoS One. 2015;10(10):e0140205.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Zhang SS, Xu XX, Xiang WW, Zhang HH, Lin HL, Shen LE, et al. Using 17β-estradiol heparin-poloxamer thermosensitive hydrogel to enhance the endometrial regeneration and functional recovery of intrauterine adhesions in a rat model. The FASEB Journal. 2020;34(1):446–57.

    Article  CAS  PubMed  Google Scholar 

  48. Yao Q, Zheng YW, Lan QH, Wang LF, Huang ZW, Chen R, et al. Aloe/poloxamer hydrogel as an injectable β-estradiol delivery scaffold with multi-therapeutic effects to promote endometrial regeneration for intrauterine adhesion treatment. Eur J Pharm Sci. 2020;148:105316.

    Article  CAS  PubMed  Google Scholar 

  49. Wenbo Q, Lijian X, Shuangdan Z, Jiahua Z, Yanpeng T, Xuejun Q, et al. Controlled releasing of SDF-1α in chitosan-heparin hydrogel for endometrium injury healing in rat model. Int J Biol Macromol. 2020;143:163–72.

    Article  PubMed  Google Scholar 

  50. Paul K, Darzi S, McPhee G, del Borgo MP, Werkmeister JA, Gargett CE, et al. 3D bioprinted endometrial stem cells on melt electrospun poly ε-caprolactone mesh for pelvic floor application promote anti-inflammatory responses in mice. Acta Biomater. 2019;97:162–76.

    Article  CAS  PubMed  Google Scholar 

  51. Paul K, et al. 3D bioprinted endometrial stem cells on melt electrospun PCL meshes for pelvic floor application promote anti-inflammatory responses in mice. Available at SSRN. 2019;3387674.

  52. Kim YY, Park KH, Kim YJ, Kim MS, Liu HC, Rosenwaks Z, et al. Synergistic regenerative effects of functionalized endometrial stromal cells with hyaluronic acid hydrogel in a murine model of uterine damage. Acta Biomater. 2019;89:139–51.

    Article  CAS  PubMed  Google Scholar 

  53. Bus A, van Hoeck V, Langbeen A, Leroy JLMR, Bols PEJ. Effects of vitrification on the viability of alginate encapsulated isolated bovine pre-antral follicles. J Assist Reprod Genet. 2018;35(7):1187–99.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Day JR, David A, Cichon AL, Kulkarni T, Cascalho M, Shikanov A. Immunoisolating poly(ethylene glycol) based capsules support ovarian tissue survival to restore endocrine function. J Biomed Mater Res A. 2018;106(5):1381–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Pors SE, Ramløse M, Nikiforov D, Lundsgaard K, Cheng J, Andersen CY, et al. Initial steps in reconstruction of the human ovary: survival of pre-antral stage follicles in a decellularized human ovarian scaffold. Hum Reprod. 2019;34(8):1523–35.

    Article  CAS  PubMed  Google Scholar 

  56. Laronda MM, Jakus AE, Whelan KA, Wertheim JA, Shah RN, Woodruff TK. Initiation of puberty in mice following decellularized ovary transplant. Biomaterials. 2015;50:20–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Mirzaeian L, et al. Optimizing the cell seeding protocol to human decellularized ovarian scaffold: application of dynamic system for bio-engineering. Cell J (Yakhteh). 2020;22(2).

  58. Jamalzaei P, Valojerdi MR, Montazeri L, Baharvand H. Effects of alginate concentration and ovarian cells on in vitro development of mouse preantral follicles: a factorial study. Int J Fertil Steril. 2020;13(4):330–8.

    CAS  PubMed  Google Scholar 

  59. Nagashima JB, Wildt DE, Travis AJ, Songsasen N. Activin promotes growth and antral cavity expansion in the dog ovarian follicle. Theriogenology. 2019;129:168–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sittadjody S, Saul JM, McQuilling JP, Joo S, Register TC, Yoo JJ, et al. In vivo transplantation of 3D encapsulated ovarian constructs in rats corrects abnormalities of ovarian failure. Nat Commun. 2017;8(1):1858.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Laronda MM, et al. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nat Commun. 2017;8(1):1–10.

    Article  Google Scholar 

  62. Kim YY, Tamadon A, Ku SY. Potential use of antiapoptotic proteins and noncoding RNAs for efficient in vitro follicular maturation and ovarian bioengineering. Tissue Eng Part B Rev. 2017;23(2):142–58.

    Article  CAS  PubMed  Google Scholar 

  63. Gilula NB, Epstein ML, Beers WH. Cell-to-cell communication and ovulation. A study of the cumulus-oocyte complex. J Cell Biol. 1978;78(1):58–75.

    Article  CAS  PubMed  Google Scholar 

  64. West ER, Shea LD, Woodruff TK. Engineering the follicle microenvironment. Semin Reprod Med. 2007;25(4):287–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Desai N, Alex A, AbdelHafez F, Calabro A, Goldfarb J, Fleischman A, et al. Three-dimensional in vitro follicle growth: overview of culture models, biomaterials, design parameters and future directions. Reprod Biol Endocrinol. 2010;8:119.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Park KE, Kim YY, Ku SY, Baek SM, Huh Y, Kim YJ, et al. Effects of alginate hydrogels on in vitro maturation outcome of mouse preantral follicles. Tissue Eng Regen Med. 2012;9(3):170–4.

    Article  CAS  Google Scholar 

  67. Rowley JA, Madlambayan G, Mooney DJ. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials. 1999;20(1):45–53.

    Article  CAS  PubMed  Google Scholar 

  68. Park KE, Ku SY, Jung KC, Liu HC, Kim YY, Kim YJ, et al. Effects of urinary and recombinant gonadotropins on in vitro maturation outcomes of mouse preantral follicles. Reprod Sci. 2013;20(8):909–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kim YJ, Kim YY, Kang BC, Kim MS, Ko IK, Liu HC, et al. Induction of multiple ovulation via modulation of angiotensin II receptors in in vitro ovarian follicle culture models. J Tissue Eng Regen Med. 2017;11(11):3100–10.

    Article  CAS  PubMed  Google Scholar 

  70. Kim YJ, Ku SY, Kim YY, Liu HC, Chi SW, Kim SH, et al. MicroRNAs transfected into granulosa cells may regulate oocyte meiotic competence during in vitro maturation of mouse follicles. Hum Reprod. 2013;28(11):3050–61.

    Article  CAS  PubMed  Google Scholar 

  71. Kim YJ, Ku SY, Rosenwaks Z, Liu HC, Chi SW, Kang JS, et al. MicroRNA expression profiles are altered by gonadotropins and vitamin C status during in vitro follicular growth. Reprod Sci. 2010;17(12):1081–9.

    Article  CAS  PubMed  Google Scholar 

  72. Kim YJ, Park KE, Kim YY, Kim H, Ku SY, Suh CS, et al. Effects of estradiol on the paracrine regulator expression of in vitro maturated murine ovarian follicles. Tissue Eng Regen Med. 2017;14(1):31–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Xu M, West-Farrell ER, Stouffer RL, Shea LD, Woodruff TK, Zelinski MB. Encapsulated three-dimensional culture supports development of nonhuman primate secondary follicles. Biol Reprod. 2009;81(3):587–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Camboni A, van Langendonckt A, Donnez J, Vanacker J, Dolmans MM, Amorim CA. Alginate beads as a tool to handle, cryopreserve and culture isolated human primordial/primary follicles. Cryobiology. 2013;67(1):64–9.

    Article  CAS  PubMed  Google Scholar 

  75. King SM, et al. Alginate hydrogels for three-dimensional organ culture of ovaries and oviducts. J Vis Exp. 2011;52.

  76. Laronda MM, Duncan FE, Hornick JE, Xu M, Pahnke JE, Whelan KA, et al. Alginate encapsulation supports the growth and differentiation of human primordial follicles within ovarian cortical tissue. J Assist Reprod Genet. 2014;31(8):1013–28.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Vanacker J, Amorim CA. Alginate: a versatile biomaterial to encapsulate isolated ovarian follicles. Ann Biomed Eng. 2017;45(7):1633–49.

    Article  PubMed  Google Scholar 

  78. Vanacker J, Luyckx V, Dolmans MM, Des Rieux A, Jaeger J, van Langendonckt A, et al. Transplantation of an alginate-matrigel matrix containing isolated ovarian cells: first step in developing a biodegradable scaffold to transplant isolated preantral follicles and ovarian cells. Biomaterials. 2012;33(26):6079–85.

    Article  CAS  PubMed  Google Scholar 

  79. Ahn JI, Kim GA, Kwon HS, Ahn JY, Hubbell JA, Song YS, et al. Culture of preantral follicles in poly(ethylene) glycol-based, three-dimensional hydrogel: a relationship between swelling ratio and follicular developments. J Tissue Eng Regen Med. 2015;9(3):319–23.

    Article  CAS  PubMed  Google Scholar 

  80. Lerer-Serfaty G, Samara N, Fisch B, Shachar M, Kossover O, Seliktar D, et al. Attempted application of bioengineered/biosynthetic supporting matrices with phosphatidylinositol-trisphosphate-enhancing substances to organ culture of human primordial follicles. J Assist Reprod Genet. 2013;30(10):1279–88.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Brito IR, Silva GM, Sales AD, Lobo CH, Rodrigues GQ, Sousa RF, et al. Fibrin-alginate hydrogel supports steroidogenesis, in vitro maturation of oocytes and parthenotes production from caprine preantral follicles cultured in group. Reprod Domest Anim. 2016;51(6):997–1009.

    Article  CAS  PubMed  Google Scholar 

  82. Jin SY, Lei L, Shikanov A, Shea LD, Woodruff TK. A novel two-step strategy for in vitro culture of early-stage ovarian follicles in the mouse. Fertil Steril. 2010;93(8):2633–9.

    Article  PubMed  Google Scholar 

  83. Wang T-r, et al. Basic fibroblast growth factor promotes the development of human ovarian early follicles during growth in vitro. Hum Reprod. 2014;29(3):568–76.

    Article  CAS  PubMed  Google Scholar 

  84. Gao J, Huang Y, Li M, Zhao H, Zhao Y, Li R, et al. Effect of local basic fibroblast growth factor and vascular endothelial growth factor on subcutaneously allotransplanted ovarian tissue in ovariectomized mice. PLoS One. 2015;10(7):e0134035.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Felder S, Masasa H, Orenbuch A, Levaot N, Shachar Goldenberg M, Cohen S. Reconstruction of the ovary microenvironment utilizing macroporous scaffold with affinity-bound growth factors. Biomaterials. 2019;205:11–22.

    Article  CAS  PubMed  Google Scholar 

  86. Tagler D, Tu T, Smith RM, Anderson NR, Tingen CM, Woodruff TK, et al. Embryonic fibroblasts enable the culture of primary ovarian follicles within alginate hydrogels. Tissue Eng Part A. 2012;18(11-12):1229–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Mendez U, Zhou H, Shikanov A. Synthetic PEG hydrogel for engineering the environment of ovarian follicles. Methods Mol Biol. 2018;1758:115–28.

    Article  CAS  PubMed  Google Scholar 

  88. Kim J, Perez AS, Claflin J, David A, Zhou H, Shikanov A. Synthetic hydrogel supports the function and regeneration of artificial ovarian tissue in mice. NPJ Regen Med. 2016;1.

  89. Buckenmeyer MJ, et al. Bioengineering an in situ ovary (ISO) for fertility preservation. bioRxiv. 2020.

  90. Kandaswamy R, Stock PG, Gustafson SK, Skeans MA, Curry MA, Prentice MA, et al. OPTN/SRTR 2016 annual data report: pancreas. Am J Transplant. 2018;18:114–71.

    Article  PubMed  Google Scholar 

  91. David A, Day J, Shikanov A. Immunoisolation to prevent tissue graft rejection: current knowledge and future use. Exp Biol Med (Maywood). 2016;241(9):955–61.

    Article  CAS  Google Scholar 

  92. Rios PD, Kniazeva E, Lee HC, Xiao S, Oakes RS, Saito E, et al. Retrievable hydrogels for ovarian follicle transplantation and oocyte collection. Biotechnol Bioeng. 2018;115(8):2075–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JAV, et al. Treatment of symptoms of the menopause: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(11):3975–4011.

    Article  CAS  PubMed  Google Scholar 

  94. Beral V, Bull D, Reeves G, Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2005;365(9470):1543–51.

    Article  PubMed  Google Scholar 

  95. Kim SW, Kim H, Ku SY, Suh CS, Kim SH, Choi YM. A successful live birth with in vitro fertilization and thawed embryo transfer after conservative treatment of recurrent endometrial cancer. Gynecol Endocrinol. 2018;34(1):15–9.

    Article  PubMed  Google Scholar 

  96. Sittadjody S, Enck KM, Wells A, Yoo JJ, Atala A, Saul JM, et al. Encapsulation of mesenchymal stem cells in 3D ovarian cell constructs promotes stable and long-term hormone secretion with improved physiological outcomes in a syngeneic rat model. Ann Biomed Eng. 2020;48(3):1058–70.

    Article  PubMed  Google Scholar 

  97. Araujo VR, et al. In vitro development of bovine secondary follicles in two- and three-dimensional culture systems using vascular endothelial growth factor, insulin-like growth factor-1, and growth hormone. Theriogenology. 2014;82(9):1246–53.

    Article  CAS  PubMed  Google Scholar 

  98. Songsasen N, Woodruff TK, Wildt DE. In vitro growth and steroidogenesis of dog follicles are influenced by the physical and hormonal microenvironment. Reproduction. 2011;142(1):113–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Xu J, Lawson MS, Yeoman RR, Molskness TA, Ting AY, Stouffer RL, et al. Fibrin promotes development and function of macaque primary follicles during encapsulated three-dimensional culture. Hum Reprod. 2013;28(8):2187–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Xu M, Fazleabas AT, Shikanov A, Jackson E, Barrett SL, Hirshfeld-Cytron J, et al. In vitro oocyte maturation and preantral follicle culture from the luteal-phase baboon ovary produce mature oocytes. Biol Reprod. 2011;84(4):689–97.

    Article  CAS  PubMed  Google Scholar 

  101. Cho E, Kim YY, Noh K, Ku SY. A new possibility in fertility preservation: the artificial ovary. J Tissue Eng Regen Med. 2019;13(8):1294–315.

    Article  CAS  PubMed  Google Scholar 

  102. Badylak SF, Taylor D, Uygun K. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng. 2011;13:27–53.

    Article  CAS  PubMed  Google Scholar 

  103. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials. 2011;32(12):3233–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomaterials. 2006;27(19):3675–83.

    CAS  PubMed  Google Scholar 

  105. Nakayama KH, Lee CCI, Batchelder CA, Tarantal AF. Tissue specificity of decellularized rhesus monkey kidney and lung scaffolds. PLoS One. 2013;8(5):e64134.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, et al. Tissue-engineered lungs for in vivo implantation. Science. 2010;329(5991):538–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Donnez J, Silber S, Andersen CY, Demeestere I, Piver P, Meirow D, et al. Children born after autotransplantation of cryopreserved ovarian tissue. a review of 13 live births. Ann Med. 2011;43(6):437–50.

    Article  PubMed  Google Scholar 

  108. Meirow D, Hardan I, Dor J, Fridman E, Elizur S, Ra'anani H, et al. Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Hum Reprod. 2008;23(5):1007–13.

    Article  PubMed  Google Scholar 

  109. Rosendahl M, Andersen MT, Ralfkiær E, Kjeldsen L, Andersen MK, Andersen CY. Evidence of residual disease in cryopreserved ovarian cortex from female patients with leukemia. Fertil Steril. 2010;94(6):2186–90.

    Article  PubMed  Google Scholar 

  110. Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology. 2011;53(2):604–17.

    Article  CAS  PubMed  Google Scholar 

  111. Ross EA, Williams MJ, Hamazaki T, Terada N, Clapp WL, Adin C, et al. Embryonic stem cells proliferate and differentiate when seeded into kidney scaffolds. J Am Soc Nephrol. 2009;20(11):2338–47.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Uygun BE, Soto-Gutierrez A, Yagi H, Izamis ML, Guzzardi MA, Shulman C, et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010;16(7):814–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Mirzaeian L, Eivazkhani F, Hezavehei M, Moini A, Esfandiari F, Valojerdi MR, et al. Optimizing the cell seeding protocol to human decellularized ovarian scaffold: application of dynamic system for bio-engineering. Cell J. 2020;22(2):227–35.

    PubMed  Google Scholar 

  114. Padma AM, Tiemann TT, Alshaikh AB, Akouri R, Song MJ, Hellström M. Protocols for rat uterus isolation and decellularization: applications for uterus tissue engineering and 3D cell culturing. Methods Mol Biol. 2018;1577:161–75.

    Article  CAS  PubMed  Google Scholar 

  115. Hellstrom M, et al. Towards the development of a bioengineered uterus: comparison of different protocols for rat uterus decellularization. Acta Biomater. 2014;10(12):5034–42.

    Article  CAS  PubMed  Google Scholar 

  116. Baert Y, Goossens E. Preparation of scaffolds from decellularized testicular matrix. Methods Mol Biol. 2018;1577:121–7.

    Article  CAS  PubMed  Google Scholar 

  117. Rezaei Topraggaleh T, Rezazadeh Valojerdi M, Montazeri L, Baharvand H. A testis-derived macroporous 3D scaffold as a platform for the generation of mouse testicular organoids. Biomater Sci. 2019;7(4):1422–36.

    Article  CAS  PubMed  Google Scholar 

  118. Olalekan SA, Burdette JE, Getsios S, Woodruff TK, Kim JJ. Development of a novel human recellularized endometrium that responds to a 28-day hormone treatment. Biol Reprod. 2017;96(5):971–81.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Nichols JE, Niles J, Riddle M, Vargas G, Schilagard T, Ma L, et al. Production and assessment of decellularized pig and human lung scaffolds. Tissue Eng Part A. 2013;19(17-18):2045–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. O’Neill JD, et al. Decellularization of human and porcine lung tissues for pulmonary tissue engineering. Ann Thorac Surg. 2013;96(3):1046–55 discussion 1055-6.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Sullivan DC, Mirmalek-Sani SH, Deegan DB, Baptista PM, Aboushwareb T, Atala A, et al. Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system. Biomaterials. 2012;33(31):7756–64.

    Article  CAS  PubMed  Google Scholar 

  122. Ghaedi M, Calle EA, Mendez JJ, Gard AL, Balestrini J, Booth A, et al. Human iPS cell-derived alveolar epithelium repopulates lung extracellular matrix. J Clin Invest. 2013;123(11):4950–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Oktay K, et al. First pregnancies, live birth, and in vitro fertilization outcomes after transplantation of frozen-banked ovarian tissue with a human extracellular matrix scaffold using robot-assisted minimally invasive surgery. Am J Obstet Gynecol. 2016;214(1):94 e1–9.

    Article  Google Scholar 

  124. La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Updat. 2014;20(1):124–40.

    Article  Google Scholar 

  125. Villalona GA, Udelsman B, Duncan DR, McGillicuddy E, Sawh-Martinez RF, Hibino N, et al. Cell-seeding techniques in vascular tissue engineering. Tissue Eng Part B Rev. 2010;16(3):341–50.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Pennarossa G, Ghiringhelli M, Gandolfi F, Brevini TAL. Whole-ovary decellularization generates an effective 3D bioscaffold for ovarian bioengineering. J Assist Reprod Genet. 2020;37(6):1329–39.

    Article  PubMed  Google Scholar 

  127. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14(2):213–21.

    Article  CAS  PubMed  Google Scholar 

  128. Uygun BE, Soto-Gutierrez A, Yagi H, Izamis ML, Guzzardi MA, Shulman C, et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010;16(7):814–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Cortiella J, Niles J, Cantu A, Brettler A, Pham A, Vargas G, et al. Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation. Tissue Eng Part A. 2010;16(8):2565–80.

    Article  CAS  PubMed  Google Scholar 

  130. Niklason L, Gao J, Abbott WM, Hirschi KK, Houser S, Marini R, et al. Functional arteries grown in vitro. Science. 1999;284(5413):489–93.

    Article  CAS  PubMed  Google Scholar 

  131. Mayorca-Guiliani AE, Madsen CD, Cox TR, Horton ER, Venning FA, Erler JT. ISDoT: in situ decellularization of tissues for high-resolution imaging and proteomic analysis of native extracellular matrix. Nat Med. 2017;23(7):890–8.

    Article  CAS  PubMed  Google Scholar 

  132. Calle EA, Hill RC, Leiby KL, le AV, Gard AL, Madri JA, et al. Targeted proteomics effectively quantifies differences between native lung and detergent-decellularized lung extracellular matrices. Acta Biomater. 2016;46:91–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Henning NF, LeDuc RD, Even KA, Laronda MM. Proteomic analyses of decellularized porcine ovaries identified new matrisome proteins and spatial differences across and within ovarian compartments. Sci Rep. 2019;9(1):20001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Thorne JT, Segal TR, Chang S, Jorge S, Segars JH, Leppert PC. Dynamic reciprocity between cells and their microenvironment in reproduction. Biol Reprod. 2015;92(1):25.

    Article  PubMed  Google Scholar 

  135. Laronda MM, Rutz AL, Xiao S, Whelan KA, Duncan FE, Roth EW, et al. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nat Commun. 2017;8:15261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Deans R, Abbott J. Review of intrauterine adhesions. J Minim Invasive Gynecol. 2010;17(5):555–69.

    Article  PubMed  Google Scholar 

  137. Yun JW, Kim YY, Ahn JH, Kang BC, Ku SY. Use of nonhuman primates for the development of bioengineered female reproductive organs. Tissue Eng Regen Med. 2016;13(4):323–34.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Kim YY, Yun JW, Kim JM, Park CG, Rosenwaks Z, Liu HC, et al. Gonadotropin ratio affects the in vitro growth of rhesus ovarian preantral follicles. J Investig Med. 2016;64(4):888–93.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Brännström M, Johannesson L, Bokström H, Kvarnström N, Mölne J, Dahm-Kähler P, et al. Livebirth after uterus transplantation. The Lancet. 2015;385(9968):607–16.

    Article  Google Scholar 

  140. Rogozea L, Sechel G, Fleancu A. Ethical aspects in bioengineering research. in WSEAS International Conference. Proceedings. Mathematics and Computers in Science and Engineering. World Sci Eng Acad Soc. 2009.

  141. van Kasteren YM, Schoemaker J. Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum Reprod Updat. 1999;5(5):483–92.

    Article  Google Scholar 

Download references

Code Availability

Not applicable.

Funding

 This study was supported by National Research Foundation of Korea (NRF) grant (2020R1A2C1010293) from Korean Government (MSIT) Fund and grant (No. 04-2015-0910) from the SNUH Research Fund.

Author information

Author notes

  1. Yoon Young Kim and Hoon Kim contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, 03080, South Korea

    Sung Woo Kim, Yoon Young Kim, Hoon Kim & Seung-Yup Ku

  2. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea

    Sung Woo Kim, Yoon Young Kim, Hoon Kim & Seung-Yup Ku

  3. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, 2024 E. Monument St, Baltimore, MD, 21205, USA

    Hoon Kim

Authors
  1. Sung Woo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoon Young Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seung-Yup Ku
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K.S.W: drafting the article, conception or design of the work, data collection, data analysis, and interpretation; K.Y.Y: drafting the article, critical revision of the article; K.H: data analysis and interpretation, final approval of the version to be published; Ku S.Y: data analysis and interpretation, conception or design of the work.

Corresponding authors

Correspondence to Yoon Young Kim or Hoon Kim.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Conflict of Interest

The 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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, S.W., Kim, Y.Y., Kim, H. et al. Recent Advancements in Engineered Biomaterials for the Regeneration of Female Reproductive Organs. Reprod. Sci. 28, 1612–1625 (2021). https://doi.org/10.1007/s43032-021-00553-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-021-00553-y

Keywords

Search

Navigation