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New Solutions for Old Problems: How Reproductive Tissue Engineering Has Been Revolutionizing Reproductive Medicine

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Abstract

Acquired disorders and congenital defects of the male and female reproductive systems can have profound impacts on patients, causing sexual and endocrine dysfunction and infertility, as well as psychosocial consequences that affect their self-esteem, identity, sexuality, and relationships. Reproductive tissue engineering (REPROTEN) is a promising approach to restore fertility and improve the quality of life of patients with reproductive disorders by developing, replacing, or regenerating cells, tissues, and organs from the reproductive and urinary systems. In this review, we explore the latest advancements in REPROTEN techniques and their applications for addressing degenerative conditions in male and female reproductive organs. We discuss current research and clinical outcomes and highlight the potential of 3D constructs utilizing biomaterials such as scaffolds, cells, and biologically active molecules. Our review offers a comprehensive guide for researchers and clinicians, providing insights into how to reestablish reproductive tissue structure and function using innovative surgical approaches and biomaterials. We highlight the benefits of REPROTEN for patients, including preservation of fertility and hormonal production, reconstruction of uterine and cervical structures, and restoration of sexual and urinary functions. Despite significant progress, REPROTEN still faces ethical and technical challenges that need to be addressed. Our review underscores the importance of continued research in this field to advance the development of effective and safe REPROTEN approaches for patients with reproductive disorders.

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Fig. 1
Fig. 2

Adapted from Alves-Lopes et al. [6] and Gholami et al. [77]. Created with BioRender.com

Fig. 3

Reprinted with permission from Hellström et al. [29, 30, 48, 86, 87, 90, 145, 147, 153, 179, 201, 223, 230] © Elsevier (2022)Reprinted with permission from Hellström et al. [29, 30, 48, 86, 87, 90, 145, 147, 153, 179, 201, 223, 230] © Elsevier (2022)

Fig. 4

Reprinted and adapted with permission from Raya-Rivera et al. [170] © Elsevier (2022)

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References

  1. Al Abbar, A., S. C. Ngai, N. Nograles, S. Y. Alhaji, and S. Abdullah. Induced pluripotent stem cells: reprogramming platforms and applications in cell replacement therapy. Biores Open Access. 9:121–136, 2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Abu Elhija, M., E. Lunenfeld, S. Schlatt, and M. Huleihel. Differentiation of murine male germ cells to spermatozoa in a soft agar culture system. Asian J. Androl. 14:285–293, 2012.

    Article  CAS  PubMed  Google Scholar 

  3. Adamowicz, J., K. Juszczak, A. Bajek, J. Tworkiewicz, M. Nowacki, A. Marszalek, P. J. Thor, P. Chlosta, and T. Drewa. Morphological and urodynamic evaluation of urinary bladder wall regeneration: muscles guarantee contraction but not proper function—a rat model research study. Transplant Proc. 44:1429–1434, 2012.

    Article  CAS  PubMed  Google Scholar 

  4. Afshar, L., H.-R. Aghayan, J. Sadighi, B. Arjmand, S.-M. Hashemi, M. Basiri, R. O. Samani, M. K. Ashtiani, S.-A. Azin, and E. Hajizadeh-Saffar. Ethics of research on stem cells and regenerative medicine: ethical guidelines in the Islamic Republic of Iran. Stem Cell Res. Ther. 11:1–5, 2020.

    Article  Google Scholar 

  5. Akbarzadeh, A., M. Kianmanesh, K. Fendereski, M. Ebadi, S. S. Daryabari, A. Masoomi, F. Ghazisaeedi, R. S. H. Beigi, R. Sheikh, and A.-M. Kajbafzadeh. Decellularised whole ovine testis as a potential bio-scaffold for tissue engineering. Reprod. Fertil. Dev. 31:1665–1673, 2019.

    Article  CAS  PubMed  Google Scholar 

  6. Alves-Lopes, J. P., O. Söder, and J.-B. Stukenborg. Testicular organoid generation by a novel in vitro three-layer gradient system. Biomaterials. 130:76–89, 2017.

    Article  CAS  PubMed  Google Scholar 

  7. Alwaal, A., U. B. Zaid, C.-S. Lin, and T. F. Lue. Stem cell treatment of erectile dysfunction. Adv. Drug Deliv. Rev. 82:137–144, 2015.

    Article  PubMed  Google Scholar 

  8. Amorim, C. A. Special issue devoted to a new field of regenerative medicine: reproductive tissue engineering. Ann. Biomed. Eng. 45:1589–1591, 2017.

    Article  PubMed  Google Scholar 

  9. Asiabi, P., M. M. Dolmans, J. Ambroise, A. Camboni, and C. A. Amorim. In vitro differentiation of theca cells from ovarian cells isolated from postmenopausal women. Hum. Reprod. 35:2793–2807, 2020.

    Article  CAS  PubMed  Google Scholar 

  10. Averill, R. L. W., and L. E. A. Rowson. Attempts at storage of sheep ova at low temperatures. J. Agric. Sci. 52:392–395, 1959.

    Article  Google Scholar 

  11. Ayta, I. A., J. B. McKinlay, and R. J. Krane. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 84:50–56, 1999.

    Article  CAS  PubMed  Google Scholar 

  12. Azami, M., J. Ai, S. Ebrahimi-Barough, M. Farokhi, and S. E. Fard. In vitro evaluation of biomimetic nanocomposite scaffold using endometrial stem cell derived osteoblast-like cells. Tissue Cell. 45:328–337, 2013.

    Article  CAS  PubMed  Google Scholar 

  13. Bahk, J. Y., J. H. Jung, H. Han, S. K. Min, and Y. S. Lee. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp. Clin. Transplant. 8:150–160, 2010.

    PubMed  Google Scholar 

  14. Baker, H. B., J. P. McQuilling, and N. M. P. King. Ethical considerations in tissue engineering research: case studies in translation. Methods. 99:135–144, 2016.

    Article  CAS  PubMed  Google Scholar 

  15. Barberini, F., E. Vizza, M. Montanino, S. Marcoccia, and G. Montanino. Vaginal reconstruction by skin grafts: A scanning electron microscopic evaluation. Ann. Anat. 174:517–522, 1992.

    Article  CAS  PubMed  Google Scholar 

  16. Bateman, C. World’s first successful penis transplant at Tygerberg Hospital. SAMJ S Afr. Med. J. 105:251–252, 2015.

    Article  PubMed  Google Scholar 

  17. Benedetti Panici, P., D. Maffucci, S. Ceccarelli, E. Vescarelli, G. Perniola, L. Muzii, and C. Marchese. Autologous in vitro cultured vaginal tissue for vaginoplasty in women with Mayer–Rokitansky–Küster–Hauser syndrome: anatomic and functional results. J. Minim. Invasive Gynecol. 22:205–211, 2015.

    Article  PubMed  Google Scholar 

  18. Berman, J. R. Physiology of female sexual function and dysfunction. Int. J. Impot. Res. 17:S44–S51, 2005.

    Article  PubMed  Google Scholar 

  19. Bivalacqua, T. J., W. Deng, M. Kendirci, M. F. Usta, C. Robinson, B. K. Taylor, S. N. Murthy, H. C. Champion, W. J. G. Hellstrom, and P. J. Kadowitz. Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction. Am. J. Physiol. Heart Circ. Physiol. 292:H1278–H1290, 2007.

    Article  CAS  PubMed  Google Scholar 

  20. Bochinski, D., G. T. Lin, L. Nunes, R. Carrion, N. Rahman, C. S. Lin, and T. F. Lue. The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int. 94:904–909, 2004.

    Article  PubMed  Google Scholar 

  21. Boretto, M., B. Cox, M. Noben, N. Hendriks, A. Fassbender, H. Roose, F. Amant, D. Timmerman, C. Tomassetti, A. Vanhie, C. Meuleman, M. Ferrante, and H. Vankelecom. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Development. 144:1775–1786, 2017.

    CAS  PubMed  Google Scholar 

  22. Bouman, M., M. C. T. van Zeijl, M. E. Buncamper, W. J. H. J. Meijerink, A. A. van Bodegraven, and M. G. Mullender. Intestinal vaginoplasty revisited: a review of surgical techniques, complications, and sexual function. J. Sex Med. 11:1835–1847, 2014.

    Article  PubMed  Google Scholar 

  23. Brännström, M., M. A. Belfort, and J. M. Ayoubi. Uterus transplantation worldwide: clinical activities and outcomes. Curr. Opin. Organ Transplant. 26(6):616–626, 2021.

    Article  PubMed  Google Scholar 

  24. Brännström, M., L. Johannesson, H. Bokström, N. Kvarnström, J. Mölne, P. Dahm-Kähler, A. Enskog, M. Milenkovic, J. Ekberg, and C. Diaz-Garcia. Livebirth after uterus transplantation. Lancet. 385:607–616, 2015.

    Article  PubMed  Google Scholar 

  25. Bretan, P. N., Jr. History of the prosthetic treatment of impotence. Urol. Clin. N. Am. 16:1–5, 1989.

    Article  Google Scholar 

  26. Brito, I. R., G. M. Silva, A. D. Sales, C. H. Lobo, G. Q. Rodrigues, R. F. Sousa, A. A. A. Moura, C. E. M. Calderón, M. Bertolini, and C. C. Campello. Fibrin–alginate hydrogel supports steroidogenesis, in vitro maturation of oocytes and parthenotes production from caprine preantral follicles cultured in group. Reprod. Domest. Anim. 51:997–1009, 2016.

    Article  CAS  PubMed  Google Scholar 

  27. Buncamper, M. E., W. B. van der Sluis, R. S. D. van der Pas, M. Özer, J. M. Smit, B. I. Witte, M.-B. Bouman, and M. G. Mullender. Surgical outcome after penile inversion vaginoplasty: a retrospective study of 475 transgender women. Plast. Reconstr. Surg. 138:999–1007, 2016.

    Article  CAS  PubMed  Google Scholar 

  28. Bunge, R. G., and J. K. Sherman. Fertilizing capacity of frozen human spermatozoa. Nature. 172:767–768, 1953.

    Article  CAS  PubMed  Google Scholar 

  29. Campo, H., P. M. Baptista, N. López-Pérez, A. Faus, I. Cervelló, and C. Simón. De- and recellularization of the pig uterus: a bioengineering pilot study. Biol. Reprod. 96:34–45, 2017.

    Article  PubMed  Google Scholar 

  30. Campo, H., X. García-Domínguez, S. López-Martínez, A. Faus, J. S. Vicente Antón, F. Marco-Jiménez, and I. Cervelló. Tissue-specific decellularized endometrial substratum mimicking different physiological conditions influences in vitro embryo development in a rabbit model. Acta Biomater. 89:126–138, 2019.

    Article  CAS  PubMed  Google Scholar 

  31. Cao, Y., H. Sun, H. Zhu, X. Zhu, X. Tang, G. Yan, J. Wang, D. Bai, J. Wang, L. Wang, Q. Zhou, H. Wang, C. Dai, L. Ding, B. Xu, Y. Zhou, J. Hao, J. Dai, and Y. Hu. Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase I clinical trial. Stem Cell Res. Ther. 9:192, 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Carroll, J., and R. G. Gosden. Physiology: transplantation of frozen—thawed mouse primordial follicles. Hum. Reprod. 8:1163–1167, 1993.

    Article  CAS  PubMed  Google Scholar 

  33. Castiglione, F., P. Hedlund, F. Van der Aa, T. J. Bivalacqua, P. Rigatti, H. Van Poppel, F. Montorsi, D. De Ridder, and M. Albersen. Intratunical injection of human adipose tissue-derived stem cells prevents fibrosis and is associated with improved erectile function in a rat model of Peyronie’s disease. Eur. Urol. 63:551–560, 2013.

    Article  CAS  PubMed  Google Scholar 

  34. Chalmers, D. R. C., and D. Nicol. Embryonic stem cell research: can the law balance ethical, scientific and economic values?(part 1). Law Hum. Genome Rev. 18:43–53, 2003.

    Google Scholar 

  35. Chalmers, D., P. Rathjen, J. Rathjen, and D. Nicol. Ethics and governance of stem cell banks. Methods Mol. Biol. 1590:99–112, 2017.

    Article  CAS  PubMed  Google Scholar 

  36. Chen, H.-X., S. Yang, Y. Ning, H.-H. Shao, M. Ma, R.-H. Tian, Y.-F. Liu, W.-Q. Gao, Z. Li, and W.-L. Xia. Novel double-layer silastic testicular prosthesis with controlled release of testosterone in vitro, and its effects on castrated rats. Asian J. Androl. 19:433–438, 2017.

    Article  CAS  PubMed  Google Scholar 

  37. Chen, K.-L., D. Eberli, J. J. Yoo, and A. Atala. Bioengineered corporal tissue for structural and functional restoration of the penis. Proc. Natl Acad. Sci. U.S.A. 107:3346–3350, 2010.

    Article  CAS  PubMed  Google Scholar 

  38. Chen, W., H. Zhou, M. D. Weir, C. Bao, and H. H. K. Xu. Umbilical cord stem cells released from alginate–fibrin microbeads inside macroporous and biofunctionalized calcium phosphate cement for bone regeneration. Acta Biomater. 8:2297–2306, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chen, Z., X. Han, X. Ouyang, J. Fang, X. Huang, and H. Wei. Transplantation of induced pluripotent stem cell-derived mesenchymal stem cells improved erectile dysfunction induced by cavernous nerve injury. Theranostics. 9:6354–6368, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Chiti, M. C., M. M. Dolmans, C. M. Lucci, F. Paulini, J. Donnez, and C. A. Amorim. Further insights into the impact of mouse follicle stage on graft outcome in an artificial ovary environment. MHR Basic Sci. Reprod. Med. 23:381–392, 2017.

    Article  CAS  Google Scholar 

  41. Chiti, M. C., M.-M. Dolmans, M. Hobeika, A. Cernogoraz, J. Donnez, and C. A. Amorim. A modified and tailored human follicle isolation procedure improves follicle recovery and survival. J. Ovarian Res. 10:1–9, 2017.

    Article  Google Scholar 

  42. Chiti, M. C., M.-M. Dolmans, L. Mortiaux, F. Zhuge, E. Ouni, P. A. K. Shahri, E. van Ruymbeke, S.-D. Champagne, J. Donnez, and C. A. Amorim. A novel fibrin-based artificial ovary prototype resembling human ovarian tissue in terms of architecture and rigidity. J. Assist. Reprod. Genet. 35:41–48, 2018.

    Article  PubMed  Google Scholar 

  43. Chiti, M. C., M.-M. Dolmans, R. Orellana, M. Soares, F. Paulini, J. Donnez, and C. A. Amorim. Influence of follicle stage on artificial ovary outcome using fibrin as a matrix. Hum. Reprod. 31:427–435, 2016.

    Article  CAS  PubMed  Google Scholar 

  44. Chiti, M., J. Vanacker, E. Ouni, N. Tatic, A. Viswanath, A. des Rieux, M. Dolmans, L. J. White, and C. A. Amorim. Ovarian extracellular matrix-based hydrogel for human ovarian follicle survival in vivo: a pilot work. J. Biomed. Mater. Res. B Appl. Biomater. 110(5):1012–1022, 2021.

    Article  PubMed  Google Scholar 

  45. Chuang, C.-Y., M.-C. Huang, H.-F. Chen, L.-H. Tseng, C.-Y. Yu, L. Stone, H.-P. Huang, H.-N. Ho, and H.-C. Kuo. Granulosa cell-derived induced pluripotent stem cells exhibit pro-trophoblastic differentiation potential. Stem Cell Res. Ther. 6:14, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Cristofari, S., B. Bertrand, S. Leuzzi, K. Rem, J. Rausky, M. Revol, M. Atlan, and A. Stivala. Postoperative complications of male to female sex reassignment surgery: a 10-year French retrospective study. Ann. Chir. Plast. Esthet. 64(1):24–32, 2019.

    Article  CAS  PubMed  Google Scholar 

  47. Dadashzadeh, A., S. Moghassemi, A. Shavandi, and C. A. Amorim. A review on biomaterials for ovarian tissue engineering. Acta Biomater. 135:48–63, 2021.

    Article  CAS  PubMed  Google Scholar 

  48. Daryabari, S. S., A.-M. Kajbafzadeh, K. Fendereski, F. Ghorbani, M. Dehnavi, M. Rostami, B. A. Garajegayeh, and S. M. Tavangar. Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds. J. Assist. Reprod. Genet. 36:1211–1223, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Dietrich, F., and P. I. Lelkes. Fine-tuning of a three-dimensional microcarrier-based angiogenesis assay for the analysis of endothelial-mesenchymal cell co-cultures in fibrin and collagen gels. Angiogenesis. 9:111–125, 2006.

    Article  CAS  PubMed  Google Scholar 

  50. Ding, J.-X., X.-J. Chen, X. Zhang, Y. Zhang, and K.-Q. Hua. Acellular porcine small intestinal submucosa graft for cervicovaginal reconstruction in eight patients with malformation of the uterine cervix. Hum. Reprod. 29:677–682, 2014.

    Article  PubMed  Google Scholar 

  51. Ding, L., X. Li, H. Sun, J. Su, N. Lin, B. Péault, T. Song, J. Yang, J. Dai, and Y. Hu. Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus. Biomaterials. 35:4888–4900, 2014.

    Article  CAS  PubMed  Google Scholar 

  52. Dolmans, M.-M., and C. A. Amorim. FERTILITY PRESERVATION: construction and use of artificial ovaries. Reproduction. 158:F15–F25, 2019.

    Article  CAS  PubMed  Google Scholar 

  53. Dolmans, M.-M., B. Martinez-Madrid, E. Gadisseux, Y. Guiot, W. Y. Yuan, A. Torre, A. Camboni, A. van Langendonckt, and J. Donnez. Short-term transplantation of isolated human ovarian follicles and cortical tissue into nude mice. Reproduction. 134:253–262, 2007.

    Article  CAS  PubMed  Google Scholar 

  54. Dolmans, M.-M., W. Y. Yuan, A. Camboni, A. Torre, A. van Langendonckt, B. Martinez-Madrid, and J. Donnez. Development of antral follicles after xenografting of isolated small human preantral follicles. Reprod. Biomed. Online. 16:705–711, 2008.

    Article  PubMed  Google Scholar 

  55. Dorin, R. P., A. Atala, and R. E. DeFilippo. Bioengineering a vaginal replacement using a small biopsy of autologous tissue. Semin. Reprod. Med. 29(1):38–44, 2011.

    Article  PubMed  Google Scholar 

  56. Drummond, A. E. The role of steroids in follicular growth. Reprod. Biol. Endocrinol. 4:1–11, 2006.

    Article  Google Scholar 

  57. Emmerson, S., S. Mukherjee, J. Melendez-Munoz, F. Cousins, S. L. Edwards, P. Karjalainen, M. Ng, K. S. Tan, S. Darzi, K. Bhakoo, A. Rosamilia, J. A. Werkmeister, and C. E. Gargett. Composite mesh design for delivery of autologous mesenchymal stem cells influences mesh integration, exposure and biocompatibility in an ovine model of pelvic organ prolapse. Biomaterials.225:119495, 2019.

    Article  CAS  PubMed  Google Scholar 

  58. Fakhrieh, M., M. Darvish, A. Ardeshirylajimi, M. Taheri, and M. D. Omrani. Improved bladder smooth muscle cell differentiation of the mesenchymal stem cells when grown on electrospun polyacrylonitrile/polyethylene oxide nanofibrous scaffold. J. Cell Biochem. 120:15814–15822, 2019.

    Article  CAS  PubMed  Google Scholar 

  59. Fakin, R. M., and P. Giovanoli. A single-center study comparison of two different male-to-female penile skin inversion vaginoplasty techniques and their 3.5-year outcomes. J. Sex Med. 18:391–399, 2021.

    Article  PubMed  Google Scholar 

  60. Falke, G., J. J. Yoo, T. G. Kwon, R. Moreland, and A. Atala. Formation of corporal tissue architecture in vivo using human cavernosal muscle and endothelial cells seeded on collagen matrices. Tissue Eng. 9:871–879, 2003.

    Article  CAS  PubMed  Google Scholar 

  61. Fayomi, A. P., K. Peters, M. Sukhwani, H. Valli-Pulaski, G. Shetty, M. L. Meistrich, L. Houser, N. Robertson, V. Roberts, C. Ramsey, C. Hanna, J. D. Hennebold, I. Dobrinski, and K. E. Orwig. Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring. Science. 363(1314–1319):2019, 1979.

    Google Scholar 

  62. Ferenczy, A. Anatomy and histology of the uterine corpus. In Blaustein’s Pathology of the Female Genital Tract. New York: Springer, 1994, pp. 327–366.

  63. Ferrando, C. A. Adverse events associated with gender affirming vaginoplasty surgery. Am. J. Obstet. Gynecol. 223:267-e1, 2020.

    Article  PubMed  Google Scholar 

  64. Ferraz, M. A. M. M., H. H. W. Henning, T. A. E. Stout, P. L. A. M. Vos, and B. M. Gadella. Designing 3-dimensional in vitro oviduct culture systems to study mammalian fertilization and embryo production. Ann. Biomed. Eng. 45:1731–1744, 2017.

    Article  PubMed  Google Scholar 

  65. Ferraz, M. A. M. M., H. S. Rho, D. Hemerich, H. H. W. Henning, H. T. A. van Tol, M. Hölker, U. Besenfelder, M. Mokry, P. L. A. M. Vos, T. A. E. Stout, S. Le Gac, and B. M. Gadella. An oviduct-on-a-chip provides an enhanced in vitro environment for zygote genome reprogramming. Nat. Commun. 9:4934, 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  66. de Filippo, R. E., J. J. Yoo, and A. Atala. Engineering of vaginal tissue in vivo. Tissue Eng. 9:301–306, 2003.

    Article  PubMed  Google Scholar 

  67. Fitzgerald, H. C., P. Dhakal, S. K. Behura, D. J. Schust, and T. E. Spencer. Self-renewing endometrial epithelial organoids of the human uterus. Proc. Natl Acad. Sci. U.S.A. 116:23132–23142, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Fotheringham, S., K. Levanon, and R. Drapkin. Ex vivo culture of primary human fallopian tube epithelial cells. J. Vis. Exp. 2011. https://doi.org/10.3791/2728.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Francés-Herrero, E., L. De Miguel-Gómez, S. López-Martínez, H. Campo, X. Garcia-Dominguez, G. Diretto, A. Faus, J. S. Vicente, F. Marco-Jiménez, and I. Cervelló. Development of decellularized oviductal hydrogels as a support for rabbit embryo culture. Reprod. Sci. 28:1644–1658, 2021.

    Article  PubMed  Google Scholar 

  70. Francioli, S.-E., I. Martin, C.-P. Sie, R. Hagg, R. Tommasini, C. Candrian, M. Heberer, and A. Barbero. Growth factors for clinical-scale expansion of human articular chondrocytes: relevance for automated bioreactor systems. Tissue Eng. 13:1227–1234, 2007.

    Article  CAS  PubMed  Google Scholar 

  71. Freed, L. E., J. C. Marquis, A. Nohria, J. Emmanual, A. G. Mikos, and R. Langer. Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers. J. Biomed. Mater. Res. 27:11–23, 1993.

    Article  CAS  PubMed  Google Scholar 

  72. Fu, Q., and Y. Cao. Use of tissue engineering in treatment of the male genitourinary tract abnormalities. J. Sex Med. 7:1741–1746, 2010.

    Article  PubMed  Google Scholar 

  73. Gassei, K., J. Ehmcke, and S. Schlatt. Initiation of testicular tubulogenesis is controlled by neurotrophic tyrosine receptor kinases in a three-dimensional Sertoli cell aggregation assay. REPRODUCTION. 136:459–469, 2008.

    Article  CAS  PubMed  Google Scholar 

  74. Gassei, K., J. Ehmcke, M. A. Wood, W. H. Walker, and S. Schlatt. Immature rat seminiferous tubules reconstructed in vitro express markers of Sertoli cell maturation after xenografting into nude mouse hosts. Mol. Hum. Reprod. 16:97–110, 2010.

    Article  CAS  PubMed  Google Scholar 

  75. Gassei, K., S. Schlatt, and J. Ehmcke. De novo morphogenesis of seminiferous tubules from dissociated immature rat testicular cells in xenografts. J. Androl. 27:611–618, 2006.

    Article  PubMed  Google Scholar 

  76. Ghahremani-Nasab, M., E. Ghanbari, Y. Jahanbani, A. Mehdizadeh, and M. Yousefi. Premature ovarian failure and tissue engineering. J. Cell Physiol. 235:4217–4226, 2020.

    Article  CAS  PubMed  Google Scholar 

  77. Ghanbari, E., M. Khazaei, M. Ghahremani-nasab, A. Mehdizadeh, and M. Yousefi. Novel therapeutic approaches of tissue engineering in male infertility. Cell Tissue Res. 380:31–42, 2020.

    Article  PubMed  Google Scholar 

  78. Gholami, K., G. Pourmand, M. Koruji, S. Ashouri, and M. Abbasi. Organ culture of seminiferous tubules using a modified soft agar culture system. Stem Cell Res. Ther. 9:1–8, 2018.

    Article  Google Scholar 

  79. Gosden, R. G. Restitution of fertility in sterilized mice by transferring primordial ovarian follicles. Hum. Reprod. 5:117–122, 1990.

    Article  CAS  PubMed  Google Scholar 

  80. Greco, K. V., L. G. Jones, I. Obiri-Yeboa, and T. Ansari. Creation of an acellular vaginal matrix for potential vaginal augmentation and cloacal repair. J. Pediatr. Adolesc. Gynecol. 31:473–479, 2018.

    Article  PubMed  Google Scholar 

  81. Gu, X., H. Shi, E. Matz, L. Zhong, T. Long, C. Clouse, W. Li, D. Chen, H. Chung, and S. Murphy. Long-term therapeutic effect of cell therapy on improvement in erectile function in a rat model with pelvic neurovascular injury. BJU Int. 124:145–154, 2019.

    Article  CAS  PubMed  Google Scholar 

  82. Hadley, M. A., S. W. Byers, C. A. Suárez-Quian, H. K. Kleinman, and M. Dym. Extracellular matrix regulates Sertoli cell differentiation, testicular cord formation, and germ cell development in vitro. J. Cell Biol. 101:1511–1522, 1985.

    Article  CAS  PubMed  Google Scholar 

  83. Hassanpour, A., T. Talaei-Khozani, E. Kargar-Abarghouei, V. Razban, and Z. Vojdani. 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. 9:1–13, 2018.

    Article  Google Scholar 

  84. He, Y., D. Chen, L. Yang, Q. Hou, H. Ma, and X. Xu. The therapeutic potential of bone marrow mesenchymal stem cells in premature ovarian failure. Stem Cell Res. Ther. 9:1–7, 2018.

    Article  Google Scholar 

  85. Hellström, M., S. Bandstein, and M. Brännström. Uterine tissue engineering and the future of uterus transplantation. Ann. Biomed. Eng. 45:1718–1730, 2017.

    Article  PubMed  Google Scholar 

  86. Hellström, M., R. R. El-Akouri, C. Sihlbom, B. M. Olsson, J. Lengqvist, H. Bäckdahl, B. R. Johansson, M. Olausson, S. Sumitran-Holgersson, and M. Brännström. Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization. Acta Biomater. 10:5034–5042, 2014.

    Article  PubMed  Google Scholar 

  87. Hellström, M., J. M. Moreno-Moya, S. Bandstein, E. Bom, R. R. Akouri, K. Miyazaki, T. Maruyama, and M. Brännström. Bioengineered uterine tissue supports pregnancy in a rat model. Fertil. Steril. 106:487–496, 2016.

    Article  PubMed  Google Scholar 

  88. Van Hemelrijck, M., A. Kessler, S. Sollie, B. Challacombe, and K. Briggs. The global prevalence of erectile dysfunction: a review. BJU Int. 124:587–599, 2019.

    Article  PubMed  Google Scholar 

  89. Hill, K. L., P. Obrtlikova, D. F. Alvarez, J. A. King, S. A. Keirstead, J. R. Allred, and D. S. Kaufman. Human embryonic stem cell− derived vascular progenitor cells capable of endothelial and smooth muscle cell function. Exp. Hematol. 38:246–257, 2010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Hiraoka, T., Y. Hirota, T. Saito-Fujita, M. Matsuo, M. Egashira, L. Matsumoto, H. Haraguchi, S. K. Dey, K. S. Furukawa, T. Fujii, and Y. Osuga. STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation. JCI Insight.1:e87591, 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Hirschi, K. K., S. Li, and K. Roy. Induced pluripotent stem cells for regenerative medicine. Annu. Rev. Biomed. Eng. 16:277–294, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ho, M. H., S. Heydarkhan, D. Vernet, I. Kovanecz, M. G. Ferrini, N. N. Bhatia, and N. F. Gonzalez-Cadavid. Stimulating vaginal repair in rats through skeletal muscle–derived stem cells seeded on small intestinal submucosal scaffolds. Obstet. Gynecol. 114:300, 2009.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Horbach, S. E. R., M.-B. Bouman, J. M. Smit, M. Özer, M. E. Buncamper, and M. G. Mullender. Outcome of vaginoplasty in male-to-female transgenders: a systematic review of surgical techniques. J. Sex Med. 12:1499–1512, 2015.

    Article  PubMed  Google Scholar 

  94. Horvath-Pereira, B. O., G. H. D. R. Almeida, L. N. da Silva Júnior, P. G. do Nascimento, B. O. Horvath Pereira, J. V. B. T. Fireman, M. L. R. F. Pereira, A. C. O. Carreira, and M. A. Miglino. Biomaterials for testicular bioengineering: how far have we come and where do we have to go? Front. Endocrinol. (Lausanne). 14:1085872–74, 2023.

    Article  PubMed  Google Scholar 

  95. House, M., S. Tadesse-Telila, E. R. Norwitz, S. Socrate, and D. L. Kaplan. Inhibitory effect of progesterone on cervical tissue formation in a three-dimensional culture system with human cervical fibroblasts. Biol. Reprod. 90:11–18, 2014.

    Article  Google Scholar 

  96. Huang, H., X. Zhao, L. Chen, C. Xu, X. Yao, Y. Lu, L. Dai, and M. Zhang. Differentiation of human embryonic stem cells into smooth muscle cells in adherent monolayer culture. Biochem. Biophys. Res. Commun. 351:321–327, 2006.

    Article  CAS  PubMed  Google Scholar 

  97. Huh, D., and J. Seo. Systems and methods for producing micro-engineered models of the human cervix. US Patent App. 15/769,387, 2018.

  98. Jamalzaei, P., M. R. Valojerdi, L. Montazeri, and H. Baharvand. Applicability of hyaluronic acid-alginate hydrogel and ovarian cells for in vitro development of mouse preantral follicles. Cell J. Yakhteh. 22:49, 2020.

    Google Scholar 

  99. Jeon, M. J., Y. S. Choi, I. D. Kim, T. Criswell, A. Atala, J. J. Yoo, and J. D. Jackson. Engineering functional rat ovarian spheroids using granulosa and theca cells. Reprod. Sci. 28:1697–1708, 2021.

    Article  CAS  PubMed  Google Scholar 

  100. Jeon, S. H., K. R. Shrestha, R. Y. Kim, A. R. Jung, Y. H. Park, O. Kwon, G. E. Kim, S. H. Kim, K. H. Kim, and J. Y. Lee. Combination therapy using human adipose-derived stem cells on the cavernous nerve and low-energy shockwaves on the corpus cavernosum in a rat model of post-prostatectomy erectile dysfunction. Urology. 88:226.e1-226.e9, 2016.

    Article  PubMed  Google Scholar 

  101. Jin, S. Y., L. Lei, A. Shikanov, L. D. Shea, and T. K. Woodruff. A novel two-step strategy for in vitro culture of early-stage ovarian follicles in the mouse. Fertil. Steril. 93:2633–2639, 2010.

    Article  PubMed  Google Scholar 

  102. Joo, S., S.-H. Oh, S. Sittadjody, E. C. Opara, J. D. Jackson, S. J. Lee, J. J. Yoo, and A. Atala. The effect of collagen hydrogel on 3D culture of ovarian follicles. Biomed. Mater.11:065009, 2016.

    Article  PubMed  Google Scholar 

  103. Jung, D., J. Xiong, M. Ye, X. Qin, L. Li, S. Cheng, M. Luo, J. Peng, J. Dong, F. Tang, W. Shen, M. M. Matzuk, and K. Kee. In vitro differentiation of human embryonic stem cells into ovarian follicle-like cells. Nat. Commun. 8:15680, 2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Kargar-Abarghouei, E., Z. Vojdani, A. Hassanpour, S. Alaee, and T. Talaei-Khozani. Characterization, recellularization, and transplantation of rat decellularized testis scaffold with bone marrow-derived mesenchymal stem cells. Stem Cell Res. Ther. 9:324, 2018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kershen, R. T., J. J. Yoo, R. B. Moreland, R. J. Krane, and A. Atala. Reconstitution of human corpus cavernosum smooth muscle in vitro and in vivo. Tissue Eng. 8:515–524, 2002.

    Article  PubMed  Google Scholar 

  106. Kim, E. J., C. Yang, J. Lee, H. W. Youm, J. R. Lee, C. S. Suh, and S. H. Kim. The new biocompatible material for mouse ovarian follicle development in three-dimensional in vitro culture systems. Theriogenology. 144:33–40, 2020.

    Article  CAS  PubMed  Google Scholar 

  107. Kim, J., Y. P. Kong, S. M. Niedzielski, R. K. Singh, A. J. Putnam, and A. Shikanov. Characterization of the crosslinking kinetics of multi-arm poly (ethylene glycol) hydrogels formed via Michael-type addition. Soft Matter. 12:2076–2085, 2016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kim, J., A. S. Perez, J. Claflin, A. David, H. Zhou, and A. Shikanov. Synthetic hydrogel supports the function and regeneration of artificial ovarian tissue in mice. NPJ Regen. Med. 1:1–8, 2016.

    Article  Google Scholar 

  109. Kim, Y. Y., K.-H. Park, Y. J. Kim, M. S. Kim, H. C. Liu, Z. Rosenwaks, and S.-Y. Ku. Synergistic regenerative effects of functionalized endometrial stromal cells with hyaluronic acid hydrogel in a murine model of uterine damage. Acta Biomater. 89:139–151, 2019.

    Article  CAS  PubMed  Google Scholar 

  110. Kleinman, H. K., M. L. McGarvey, L. A. Liotta, P. G. Robey, K. Tryggvason, and G. R. Martin. Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. Biochemistry. 21:6188–6193, 1982.

    Article  CAS  PubMed  Google Scholar 

  111. Kniazeva, E., A. N. Hardy, S. A. Boukaidi, T. K. Woodruff, J. S. Jeruss, and L. D. Shea. Primordial follicle transplantation within designer biomaterial grafts produce live births in a mouse infertility model. Sci. Rep. 5:1–11, 2015.

    Article  Google Scholar 

  112. Koullali, B., and M. D. House. Scaffolds for cervical tissue engineering. In: Handbook of Tissue Engineering Scaffolds: Vol. 2. Elsevier, Cambridge, 2019, pp. 333–343.

  113. Krampera, M., L. Cosmi, R. Angeli, A. Pasini, F. Liotta, A. Andreini, V. Santarlasci, B. Mazzinghi, G. Pizzolo, and F. Vinante. Role for interferon-γ in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells. 24:386–398, 2006.

    Article  CAS  PubMed  Google Scholar 

  114. Kwon, T. G., J. J. Yoo, and A. Atala. Autologous penile corpora cavernosa replacement using tissue engineering techniques. J. Urol. 168:1754–1758, 2002.

    Article  CAS  PubMed  Google Scholar 

  115. Lai, D., F. Wang, X. Yao, Q. Zhang, X. Wu, and C. Xiang. Human endometrial mesenchymal stem cells restore ovarian function through improving the renewal of germline stem cells in a mouse model of premature ovarian failure. J. Transl. Med. 13:1–13, 2015.

    Article  CAS  Google Scholar 

  116. Laronda, M. M., A. E. Jakus, K. A. Whelan, J. A. Wertheim, R. N. Shah, and T. K. Woodruff. Initiation of puberty in mice following decellularized ovary transplant. Biomaterials. 50:20–29, 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Laronda, M. M., A. L. Rutz, S. Xiao, K. A. Whelan, F. E. Duncan, E. W. Roth, T. K. Woodruff, and R. N. Shah. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nat. Commun. 8:1–10, 2017.

    Article  Google Scholar 

  118. Lee, J. H., H. J. Kim, H. Kim, S. J. Lee, and M. C. Gye. In vitro spermatogenesis by three-dimensional culture of rat testicular cells in collagen gel matrix. Biomaterials. 27:2845–2853, 2006.

    Article  CAS  PubMed  Google Scholar 

  119. Lee, J. H., J. H. Oh, J. H. Lee, M. R. Kim, and C. K. Min. Evaluation of in vitro spermatogenesis using poly (d,l-lactic-co-glycolic acid)(PLGA)-based macroporous biodegradable scaffolds. J. Tissue Eng. Regen. Med. 5:130–137, 2011.

    Article  CAS  PubMed  Google Scholar 

  120. Lee, R. H., A. A. Pulin, M. J. Seo, D. J. Kota, J. Ylostalo, B. L. Larson, L. Semprun-Prieto, P. Delafontaine, and D. J. Prockop. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 5:54–63, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Leibo, S. P. The early history of gamete cryobiology. In: Life in the Frozen State. Boca Raton: CRC Press, 2004, pp. 373–396.

  122. Li, H., M. P. Matheu, F. Sun, L. Wang, M. T. Sanford, H. Ning, L. Banie, Y. Lee, Z. Xin, and Y. Guo. Low-energy shock wave therapy ameliorates erectile dysfunction in a pelvic neurovascular injuries rat model. J. Sex Med. 13:22–32, 2016.

    Article  PubMed  Google Scholar 

  123. Li, Q., J. Wang, H. Liu, B. Xie, and L. Wei. Tissue-engineered mesh for pelvic floor reconstruction fabricated from silk fibroin scaffold with adipose-derived mesenchymal stem cells. Cell Tissue Res. 354:471–480, 2013.

    Article  CAS  PubMed  Google Scholar 

  124. Li, X., H. Sun, N. Lin, X. Hou, J. Wang, B. Zhou, P. Xu, Z. Xiao, B. Chen, J. Dai, and Y. Hu. Regeneration of uterine horns in rats by collagen scaffolds loaded with collagen-binding human basic fibroblast growth factor. Biomaterials. 32:8172–8181, 2011.

    Article  CAS  PubMed  Google Scholar 

  125. Li, Y., F. Liu, Z. Zhang, M. Zhang, S. Cao, Y. Li, L. Zhang, X. Huang, and Y. Xu. Bone marrow mesenchymal stem cells could acquire the phenotypes of epithelial cells and accelerate vaginal reconstruction combined with small intestinal submucosa. Cell Biol. Int. 39:1225–1233, 2015.

    Article  CAS  PubMed  Google Scholar 

  126. Li, Y., H. Meng, Y. Liu, and B. P. Lee. Fibrin gel as an injectable biodegradable scaffold and cell carrier for tissue engineering. Sci. World J.2015:685690, 2015.

    Article  Google Scholar 

  127. Lin, W. C., C. Y. Y. Chang, Y. Y. Shen, and H. D. Tsai. Use of autologous buccal mucosa for vaginoplasty: a study of eight cases. Hum. Reprod. 18:604–607, 2003.

    Article  CAS  PubMed  Google Scholar 

  128. Lipskind, S., J. S. Lindsey, B. Gerami-Naini, J. L. Eaton, D. O’Connell, A. Kiezun, J. W. K. Ho, N. Ng, P. Parasar, M. Ng, M. Nickerson, U. Demirci, R. Maas, and R. M. Anchan. An embryonic and induced pluripotent stem cell model for ovarian granulosa cell development and steroidogenesis. Reprod. Sci. 25:712–726, 2018.

    Article  CAS  PubMed  Google Scholar 

  129. Liu, C., X. Xia, W. Miao, X. Luan, L. Sun, Y. Jin, and L. Liu. An ovarian cell microcapsule system simulating follicle structure for providing endogenous female hormones. Int. J. Pharm. 455:312–319, 2013.

    Article  CAS  PubMed  Google Scholar 

  130. Liu, F., S. Hu, H. Yang, Z. Li, K. Huang, T. Su, S. Wang, and K. Cheng. Hyaluronic acid hydrogel integrated with mesenchymal stem cell-secretome to treat endometrial injury in a rat model of Asherman’s syndrome. Adv. Healthc. Mater. 8:e1900411–e1900411, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Liu, J., H. Zhang, Y. Zhang, N. Li, Y. Wen, F. Cao, H. Ai, and X. Xue. Homing and restorative effects of bone marrow-derived mesenchymal stem cells on cisplatin injured ovaries in rats. Mol. Cells. 37:865, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Liu, T., Q. Li, S. Wang, C. Chen, and J. Zheng. Transplantation of ovarian granulosa-like cells derived from human induced pluripotent stem cells for the treatment of murine premature ovarian failure. Mol. Med. Rep. 13:5053–5058, 2016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Liverani, L., N. Raffel, A. Fattahi, A. Preis, I. Hoffmann, A. R. Boccaccini, M. W. Beckmann, and R. Dittrich. Electrospun patterned porous scaffolds for the support of ovarian follicles growth: a feasibility study. Sci. Rep. 9:1–14, 2019.

    Article  Google Scholar 

  134. López-Martínez, S., H. Campo, and I. Cervelló. Decellularization methods of vagina and cervix in tissue engineering. In: Decellularization Methods of Tissue and Whole Organ in Tissue Engineering. Cham: Springer, 2021, pp. 153–160.

  135. Löser, P., J. Schirm, A. Guhr, A. M. Wobus, and A. Kurtz. Human embryonic stem cell lines and their use in international research. Stem Cells. 28:240–246, 2010.

    Article  PubMed  Google Scholar 

  136. Luyckx, V., M.-M. Dolmans, J. Vanacker, C. Legat, C. F. Moya, J. Donnez, and C. A. Amorim. A new step toward the artificial ovary: survival and proliferation of isolated murine follicles after autologous transplantation in a fibrin scaffold. Fertil. Steril. 101:1149–1156, 2014.

    Article  PubMed  Google Scholar 

  137. Ma, L., Y. Yang, S. C. Sikka, P. J. Kadowitz, L. J. Ignarro, A. B. Abdel-Mageed, and W. J. G. Hellstrom. Adipose tissue-derived stem cell-seeded small intestinal submucosa for tunica albuginea grafting and reconstruction. Proc. Natl Acad. Sci. U.S.A. 109:2090–2095, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Magalhaes, R. S., J. K. Williams, K. W. Yoo, J. J. Yoo, and A. Atala. A tissue-engineered uterus supports live births in rabbits. Nat. Biotechnol. 38:1280–1287, 2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Mangir, N., C. Akbal, T. Tarcan, F. Simsek, and L. Turkeri. Mesenchymal stem cell therapy in treatment of erectile dysfunction: autologous or allogeneic cell sources? Int. J. Urol. 21:1280–1285, 2014.

    Article  PubMed  Google Scholar 

  140. Mao, A. S., and D. J. Mooney. Regenerative medicine: Current therapies and future directions. Proc. Natl Acad. Sci. U.S.A. 112:14452–14459, 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Maruyama, T. Stem cells in the uterus: past, present and future. Semin. Reprod. Med. 33(5):315–316, 2015.

    Article  PubMed  Google Scholar 

  142. McQuillan, S. K., and S. R. Grover. Systematic review of sexual function and satisfaction following the management of vaginal agenesis. Int. Urogynecol. J. 25:1313–1320, 2014.

    Article  PubMed  Google Scholar 

  143. Metallo, C. M., S. M. Azarin, L. Ji, J. J. de Pablo, and S. P. Palecek. Engineering tissue from human embryonic stem cells. J. Cell Mol. Med. 12:709–729, 2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Mhatre, P., J. Mhatre, and R. Sahu. New laparoscopic peritoneal pull-through vaginoplasty technique. J. Hum. Reprod. Sci. 7:181–186, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Miki, F., T. Maruyama, K. Miyazaki, T. Takao, Y. Yoshimasa, S. Katakura, H. Hihara, S. Uchida, H. Masuda, H. Uchida, T. Nagai, S. Shibata, and M. Tanaka. The orientation of a decellularized uterine scaffold determines the tissue topology and architecture of the regenerated uterus in rats. Biol. Reprod. 100:1215–1227, 2019.

    Article  PubMed  Google Scholar 

  146. Miyazaki, K., M. T. Dyson, J. S. Coon, V. Y. Furukawa, B. D. Yilmaz, T. Maruyama, and S. E. Bulun. Generation of progesterone-responsive endometrial stromal fibroblasts from human induced pluripotent stem cells: role of the WNT/CTNNB1 pathway. Stem Cell Rep. 11:1136–1155, 2018.

    Article  CAS  Google Scholar 

  147. Miyazaki, K., and T. Maruyama. Partial regeneration and reconstruction of the rat uterus through recellularization of a decellularized uterine matrix. Biomaterials. 35:8791–8800, 2014.

    Article  CAS  PubMed  Google Scholar 

  148. Mohamed, S. A., S. M. Shalaby, M. Abdelaziz, S. Brakta, W. D. Hill, N. Ismail, and A. Al-Hendy. Human mesenchymal stem cells partially reverse infertility in chemotherapy-induced ovarian failure. Reprod. Sci. 25:51–63, 2018.

    Article  CAS  PubMed  Google Scholar 

  149. Nagashima, J. B., D. E. Wildt, A. J. Travis, and N. Songsasen. Activin promotes growth and antral cavity expansion in the dog ovarian follicle. Theriogenology. 129:168–177, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Nishikawa, S., R. A. Goldstein, and C. R. Nierras. The promise of human induced pluripotent stem cells for research and therapy. Nat. Rev. Mol. Cell Biol. 9:725–729, 2008.

    Article  CAS  PubMed  Google Scholar 

  151. Nolazco, G., I. Kovanecz, D. Vernet, M. G. Ferrini, R. A. Gelfand, J. Tsao, T. R. Magee, J. Rajfer, and N. F. Gonzalez-Cadavid. Effect of muscle derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat. J. Urol. 179:335–336, 2008.

    Article  Google Scholar 

  152. Oerlemans, A. J. M., W. F. J. Feitz, E. van Leeuwen, and W. J. M. Dekkers. Regenerative urology clinical trials: an ethical assessment of road blocks and solutions. Tissue Eng. Part B Rev. 19:41–47, 2013.

    Article  CAS  PubMed  Google Scholar 

  153. Olalekan, S. A., J. E. Burdette, S. Getsios, T. K. Woodruff, and J. J. Kim. Development of a novel human recellularized endometrium that responds to a 28-day hormone treatment. Biol. Reprod. 96:971–981, 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  154. Oliver, E., J. P. Alves-Lopes, F. Harteveld, R. T. Mitchell, E. Åkesson, O. Söder, and J.-B. Stukenborg. Self-organising human gonads generated by a Matrigel-based gradient system. BMC Biol. 19:212, 2021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Osborn, S. L., R. Thangappan, A. Luria, J. H. Lee, J. Nolta, and E. A. Kurzrock. Induction of human embryonic and induced pluripotent stem cells into urothelium. Stem Cells Transl. Med. 3:610–619, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Ouni, E., D. Vertommen, M. C. Chiti, M.-M. Dolmans, and C. A. Amorim. A draft map of the human ovarian proteome for tissue engineering and clinical applications. Mol. Cell Proteomics. 18:S159–S173, 2019.

    Article  CAS  PubMed  Google Scholar 

  157. Parasar, P., C. R. Sacha, N. Ng, E. R. McGuirk, S. Chinthala, P. Ozcan, J. Lindsey, S. Salas, M. R. Laufer, S. A. Missmer, and R. M. Anchan. Differentiating mouse embryonic stem cells express markers of human endometrium. Reprod. Biol. Endocrinol. 15:52, 2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Parenteau-Bareil, R., R. Gauvin, and F. Berthod. Collagen-based biomaterials for tissue engineering applications. Materials. 3:1863–1887, 2010.

    Article  CAS  PubMed Central  Google Scholar 

  159. Park, H.-S., R. M. Chugh, A. Elsharoud, M. Ulin, S. Esfandyari, A. Aboalsoud, L. Bakir, and A. Al-Hendy. Safety of intraovarian injection of human mesenchymal stem cells in a premature ovarian insufficiency mouse model. Cell Transplant. 30:0963689720988502, 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  160. Partridge, E. A., M. G. Davey, M. A. Hornick, P. E. McGovern, A. Y. Mejaddam, J. D. Vrecenak, C. Mesas-Burgos, A. Olive, R. C. Caskey, T. R. Weiland, J. Han, A. J. Schupper, J. T. Connelly, K. C. Dysart, J. Rychik, H. L. Hedrick, W. H. Peranteau, and A. W. Flake. An extra-uterine system to physiologically support the extreme premature lamb. Nat. Commun. 8:15112, 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  161. Patel, M. N., and A. Atala. Tissue engineering of the penis. Sci. World J. 11:2567–2578, 2011.

    Article  Google Scholar 

  162. Patra, T., D. Pathak, and M. K. Gupta. Strategies for cryopreservation of testicular cells and tissues in cancer and genetic diseases. Cell Tissue Res. 385:1–19, 2021.

    Article  PubMed  Google Scholar 

  163. Paulini, F., J. M. V. Vilela, M. C. Chiti, J. Donnez, P. Jadoul, M. M. Dolmans, and C. A. Amorim. Survival and growth of human preantral follicles after cryopreservation of ovarian tissue, follicle isolation and short-term xenografting. Reprod. Biomed. Online. 33:425–432, 2015.

    Article  Google Scholar 

  164. Peng, G., H. Liu, and Y. Fan. Biomaterial scaffolds for reproductive tissue engineering. Ann. Biomed. Eng. 45:1592–1607, 2017.

    Article  PubMed  Google Scholar 

  165. de Philippo, R. E., C. E. Bishop, L. Freitas Filho, J. J. Yoo, and A. Atala. Tissue engineering a complete vaginal replacement from a small biopsy of autologous tissue. Transplantation. 86:208–214, 2008.

    Article  Google Scholar 

  166. Poels, J., G. Abou-Ghannam, A. Decamps, M. Leyman, A. des Rieux, and C. Wyns. Transplantation of testicular tissue in alginate hydrogel loaded with VEGF nanoparticles improves spermatogonial recovery. J. Control. Release. 234:79–89, 2016.

    Article  CAS  PubMed  Google Scholar 

  167. Pors, S., S. G. Kristensen, K. Lundsgaard, M. Ramlose, and C. Y. Andersen. Towards an artificial ovary: grafting preantral follicles on decellularized human ovarian tissue. Hum. Reprod.33:i39, 2018.

    Google Scholar 

  168. Pryzhkova, M. V., and P. W. Jordan. Adaptation of human testicular niche cells for pluripotent stem cell and testis development research. Tissue Eng. Regen. Med. 17:223–235, 2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Raya-Rivera, A. M., C. Baez, A. Atala, and J. J. Yoo. Tissue engineered testicular prostheses with prolonged testosterone release. World J. Urol. 26:351–358, 2008.

    Article  CAS  PubMed  Google Scholar 

  170. Raya-Rivera, A. M., D. Esquiliano, R. Fierro-Pastrana, E. López-Bayghen, P. Valencia, R. Ordorica-Flores, S. Soker, J. J. Yoo, and A. Atala. Tissue-engineered autologous vaginal organs in patients: a pilot cohort study. Lancet. 384:329–336, 2014.

    Article  PubMed  Google Scholar 

  171. Reda, A., M. Hou, L. Landreh, K. R. Kjartansdóttir, K. Svechnikov, O. Söder, and J.-B. Stukenborg. in vitro spermatogenesis—optimal culture conditions for testicular cell survival, germ cell differentiation, and steroidogenesis in rats. Front. Endocrinol. Lausanne. 5:21–24, 2014.

    PubMed  PubMed Central  Google Scholar 

  172. Richer, G., Y. Baert, and E. Goossens. In-vitro spermatogenesis through testis modelling: toward the generation of testicular organoids. Andrology. 8:879–891, 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  173. Sadri-Ardekani, H., and A. Atala. Regenerative medicine for the treatment of reproductive system disorders: current and potential options. Adv. Drug Deliv. Rev. 82:145–152, 2015.

    Article  PubMed  Google Scholar 

  174. Sadri-Ardekani, H., and A. Atala. Regenerative medicine for the male reproductive system. In: Principles of Regenerative Medicine. San Diego: Elsevier, 2019, pp. 1251–1261.

  175. Sadri-Ardekani, H., J. Jackson, and A. Atala. Male reproductive organs. In: Principles of Tissue Engineering. Elsevier, 2020, pp. 871–880.

  176. Sakib, S., A. Uchida, P. Valenzuela-Leon, Y. Yu, H. Valli-Pulaski, K. Orwig, M. Ungrin, and I. Dobrinski. Formation of organotypic testicular organoids in microwell culture. Biol. Reprod. 100:1648–1660, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  177. Salas, S., N. Ng, B. Gerami-Naini, and R. M. Anchan. Induced pluripotent stem cells from ovarian tissue. Curr. Protoc. Hum. Genet. 95:21.10.1-21.10.22, 2017.

    PubMed  Google Scholar 

  178. Salgado, A. J., J. M. Oliveira, A. Martins, F. G. Teixeira, N. A. Silva, N. M. Neves, N. Sousa, and R. L. Reis. Chapter One - Tissue Engineering and Regenerative Medicine: Past, Present, and Future. In: International Review of Neurobiology, edited by S. Geuna, I. Perroteau, P. Tos, and B. Battiston. Academic Press, 2013, pp. 1–33.

  179. Santoso, E. G., K. Yoshida, Y. Hirota, M. Aizawa, O. Yoshino, A. Kishida, Y. Osuga, S. Saito, T. Ushida, and K. S. Furukawa. Application of detergents or high hydrostatic pressure as decellularization processes in uterine tissues and their subsequent effects on in vivo uterine regeneration in murine models. PLoS ONE. 9:e103201–e103201, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  180. Sato, M., K. Kawana, K. Adachi, A. Fujimoto, M. Yoshida, H. Nakamura, H. Nishida, T. Inoue, A. Taguchi, J. Ogishima, S. Eguchi, A. Yamashita, K. Tomio, O. Wada-Hiraike, K. Oda, T. Nagamatsu, Y. Osuga, and T. Fujii. Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): a new approach to finding targets for cervical cancer stem cell treatment. Oncotarget. 8:40935–40945, 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  181. Scarritt, M. E., N. C. Pashos, and B. A. Bunnell. A review of cellularization strategies for tissue engineering of whole organs. Front. Bioeng. Biotechnol. 3:43–44, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  182. Seybold, D., T. A. Schildhauer, J. Geßmann, G. Muhr, M. Köller, and B. Roetman. Osteogenic differentiation of human mesenchymal stromal cells is promoted by a leukocytes containing fibrin matrix. Langenbecks Arch Surg. 395:719–726, 2010.

    Article  PubMed  Google Scholar 

  183. Shikanov, A., M. Xu, T. K. Woodruff, and L. D. Shea. Interpenetrating fibrin–alginate matrices for in vitro ovarian follicle development. Biomaterials. 30:5476–5485, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Simintiras, C. A., P. Dhakal, C. Ranjit, H. C. Fitzgerald, A. Z. Balboula, and T. E. Spencer. Capture and metabolomic analysis of the human endometrial epithelial organoid secretome. Proc. Natl Acad. Sci. U.S.A. 118:e2026804118, 2021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Sittadjody, S., J. M. Saul, S. Joo, J. J. Yoo, A. Atala, and E. C. Opara. Engineered multilayer ovarian tissue that secretes sex steroids and peptide hormones in response to gonadotropins. Biomaterials. 34:2412–2420, 2013.

    Article  CAS  PubMed  Google Scholar 

  186. van der Sluis, W. B., M.-B. Bouman, N. K. H. de Boer, M. E. Buncamper, A. A. van Bodegraven, E. A. Neefjes-Borst, B. P. C. Kreukels, W. J. H. J. Meijerink, and M. G. Mullender. Long-term follow-up of transgender women after secondary intestinal vaginoplasty. J. Sex Med. 13:702–710, 2016.

    Article  PubMed  Google Scholar 

  187. Smith, R. M., A. Shikanov, E. Kniazeva, D. Ramadurai, T. K. Woodruff, and L. D. Shea. Fibrin-mediated delivery of an ovarian follicle pool in a mouse model of infertility. Tissue Eng. Part A. 20:3021–3030, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Soloyan, H., R. E. De Filippo, and S. Sedrakyan. Tissue engineering of the reproductive system. In: Reference Module in Biomedical Sciences. Elsevier, 2019.

  189. Song, T., X. Zhao, H. Sun, X. Li, N. Lin, L. Ding, J. Dai, and Y. Hu. Regeneration of uterine horns in rats using collagen scaffolds loaded with human embryonic stem cell-derived endometrium-like cells. Tissue Eng. Part A. 21:353–361, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  190. Song, W., Q. Yu, L.-C. Wang, and D. C. Stein. Adaptation of Neisseria gonorrhoeae to the female reproductive tract. Microbiol. Insights. 13:1178636120947077, 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  191. Song, Y., J. Ku, E. Song, J. Kim, J. Jeon, K. Lee, S. Kim, H. Cheong, I. Lim, and D. Choi. Magnetic resonance evaluation of human mesenchymal stem cells in corpus cavernosa of rats and rabbits. Asian J. Androl. 9:361–367, 2007.

    Article  CAS  PubMed  Google Scholar 

  192. Stolp, J., M. Zaitsu, and K. J. Wood. Immune tolerance and rejection in organ transplantation. Methods Mol. Biol. 159–180:2019, 1899.

    Google Scholar 

  193. Stukenborg, J., J. Wistuba, C. M. Luetjens, M. A. Elhija, M. Huleihel, E. Lunenfeld, J. Gromoll, E. Nieschlag, and S. Schlatt. Coculture of spermatogonia with somatic cells in a novel three-dimensional soft-agar-culture-system. J. Androl. 29:312–329, 2008.

    Article  CAS  PubMed  Google Scholar 

  194. Su, J., L. Ding, J. Cheng, J. Yang, X. Li, G. Yan, H. Sun, J. Dai, and Y. Hu. Transplantation of adipose-derived stem cells combined with collagen scaffolds restores ovarian function in a rat model of premature ovarian insufficiency. Hum. Reprod. 31:1075–1086, 2016.

    Article  CAS  PubMed  Google Scholar 

  195. Sueters, J., F. Xiao, J.-P.W.R. Roovers, M.-B. Bouman, F. A. Groenman, H. Maas, J. A. F. Huirne, and T. H. Smit. Vagina reconstruction by decellularization of healthy human vaginal tissue. medRxiv. 2023. https://doi.org/10.1101/2023.04.05.23288175.

    Article  Google Scholar 

  196. Tagler, D., T. Tu, R. M. Smith, N. R. Anderson, C. M. Tingen, T. K. Woodruff, and L. D. Shea. Embryonic fibroblasts enable the culture of primary ovarian follicles within alginate hydrogels. Tissue Eng. Part A. 18:1229–1238, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Takahashi, K., and S. Yamanaka. A decade of transcription factor-mediated reprogramming to pluripotency. Nat. Rev. Mol. Cell Biol. 17:183, 2016.

    Article  CAS  PubMed  Google Scholar 

  198. Tauchmanovà, L., C. Selleri, G. De Rosa, A. Sammartino, C. Di Carlo, T. Musella, C. Martorelli, G. Lombardi, B. Rotoli, C. Nappi, and A. Colao. Estrogen-progestin therapy in women after stem cell transplant: our experience and literature review. Menopause. 14(2):320–330, 2007.

    Article  PubMed  Google Scholar 

  199. Telfer, E., C. Torrance, and R. G. Gosden. Morphological study of cultured preantral ovarian follicles of mice after transplantation under the kidney capsule. Reproduction. 89:565–571, 1990.

    Article  CAS  Google Scholar 

  200. Thoma, M. E., A. C. McLain, J. F. Louis, R. B. King, A. C. Trumble, R. Sundaram, and G. M. B. Louis. Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil. Steril. 99:1324–1331, 2013.

    Article  PubMed  PubMed Central  Google Scholar 

  201. Tiemann, T. T., A. M. Padma, E. Sehic, H. Bäckdahl, M. Oltean, M. J. Song, M. Brännström, and M. Hellström. Towards uterus tissue engineering: a comparative study of sheep uterus decellularisation. Mol. Hum. Reprod. 26:167–178, 2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Todorova, D., Y. Zhang, Q. Chen, J. Liu, J. He, X. Fu, and Y. Xu. hESC-derived immune suppressive dendritic cells induce immune tolerance of parental hESC-derived allografts. EBioMedicine.62:103120, 2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Tomaszewski, C. E., E. Constance, M. M. Lemke, H. Zhou, V. Padmanabhan, K. B. Arnold, and A. Shikanov. Adipose-derived stem cell-secreted factors promote early stage follicle development in a biomimetic matrix. Biomater. Sci. 7:571–580, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Tsou, Y.-H., J. Khoneisser, P.-C. Huang, and X. Xu. Hydrogel as a bioactive material to regulate stem cell fate. Bioact. Mater. 1:39–55, 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  205. Turco, M. Y., L. Gardner, J. Hughes, T. Cindrova-Davies, M. J. Gomez, L. Farrell, M. Hollinshead, S. G. E. Marsh, J. J. Brosens, H. O. Critchley, B. D. Simons, M. Hemberger, B.-K. Koo, A. Moffett, and G. J. Burton. Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nat. Cell Biol. 19:568–577, 2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Vardiani, M., M. Gholipourmalekabadi, M. Ghaffari Novin, M. Koruji, H. Ghasemi Hamidabadi, M. Salimi, and H. Nazarian. Three-dimensional electrospun gelatin scaffold coseeded with embryonic stem cells and sertoli cells: A promising substrate for in vitro coculture system. J. Cell Biochem. 120:12508–12518, 2019.

    Article  CAS  PubMed  Google Scholar 

  207. del Vento, F., J. Poels, M. Vermeulen, B. Ucakar, M. G. Giudice, M. Kanbar, A. des Rieux, and C. Wyns. Accelerated and improved vascular maturity after transplantation of testicular tissue in hydrogels supplemented with VEGF- and PDGF-loaded nanoparticles. Int. J. Mol. Sci. 22:5779, 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  208. Del Vento, F., M. Vermeulen, F. De Michele, M. G. Giudice, J. Poels, A. Des Rieux, and C. Wyns. Tissue engineering to improve immature testicular tissue and cell transplantation outcomes: one step closer to fertility restoration for prepubertal boys exposed to gonadotoxic treatments. Int. J. Mol. Sci. 19:286, 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  209. del Vento, F., M. Vermeulen, B. Ucakar, J. Poels, A. des Rieux, and C. Wyns. Significant benefits of nanoparticles containing a necrosis inhibitor on mice testicular tissue autografts outcomes. Int. J. Mol. Sci. 20:5833, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  210. Vermeulen, M., J. Poels, F. De Michele, A. Des Rieux, and C. Wyns. Restoring fertility with cryopreserved prepubertal testicular tissue: perspectives with hydrogel encapsulation, nanotechnology, and bioengineered scaffolds. Ann. Biomed. Eng. 45:1770–1781, 2017.

    Article  PubMed  Google Scholar 

  211. Vermeulen, M., F. del Vento, M. Kanbar, S. Pyr Dit Ruys, D. Vertommen, J. Poels, and C. Wyns. Generation of organized porcine testicular organoids in solubilized hydrogels from decellularized extracellular matrix. Int. J. Mol. Sci. 20:5476, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Vermeulen, M., F. Del Vento, F. De Michele, J. Poels, and C. Wyns. Development of a cytocompatible scaffold from pig immature testicular tissue allowing human sertoli cell attachment, proliferation and functionality. Int. J. Mol. Sci. 19:227, 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  213. Wang, H.-B., S.-H. Lü, Q.-X. Lin, L.-X. Feng, D.-X. Li, C.-M. Duan, Y. Li, and C.-Y. Wang. Reconstruction of endometrium in vitro via rabbit uterine endometrial cells expanded by sex steroid. Fertil. Steril. 93:2385–2395, 2010.

    Article  CAS  PubMed  Google Scholar 

  214. Woods, D. C., Y. A. R. White, Y. Niikura, S. Kiatpongsan, H.-J. Lee, and J. L. Tilly. Embryonic stem cell-derived granulosa cells participate in ovarian follicle formation in vitro and in vivo. Reprod. Sci. 20:524–535, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Xiao, B., W. Yang, D. Lei, J. Huang, Y. Yin, Y. Zhu, Z. You, F. Wang, and S. Sun. PGS scaffolds promote the in vivo survival and directional differentiation of bone marrow mesenchymal stem cells restoring the morphology and function of wounded rat uterus. Adv. Healthc. Mater. 8:1801455, 2019.

    Article  Google Scholar 

  216. Xiao, S., J. R. Coppeta, H. B. Rogers, B. C. Isenberg, J. Zhu, S. A. Olalekan, K. E. McKinnon, D. Dokic, A. S. Rashedi, D. J. Haisenleder, S. S. Malpani, C. A. Arnold-Murray, K. Chen, M. Jiang, L. Bai, C. T. Nguyen, J. Zhang, M. M. Laronda, T. J. Hope, K. P. Maniar, M. E. Pavone, M. J. Avram, E. C. Sefton, S. Getsios, J. E. Burdette, J. J. Kim, J. T. Borenstein, and T. K. Woodruff. A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle. Nat. Commun. 8:14584, 2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Xie, C.-Q., J. Zhang, L. Villacorta, T. Cui, H. Huang, and Y. E. Chen. A highly efficient method to differentiate smooth muscle cells from human embryonic stem cells. Arterioscler. Thromb. Vasc. Biol. 27:e311–e312, 2007.

    Article  CAS  PubMed  Google Scholar 

  218. Xin, L., X. Lin, Y. Pan, X. Zheng, L. Shi, Y. Zhang, L. Ma, C. Gao, and S. Zhang. A collagen scaffold loaded with human umbilical cord-derived mesenchymal stem cells facilitates endometrial regeneration and restores fertility. Acta Biomater. 92:160–171, 2019.

    Article  CAS  PubMed  Google Scholar 

  219. Xu, M., P. K. Kreeger, L. D. Shea, and T. K. Woodruff. Tissue-engineered follicles produce live fertile, offspring. Tissue Eng. 12:2739–2746, 2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Xue, B., D. Liu, M. Song, G. Zhao, Y. Cao, G. Yan, J. Dai, and Y. Hu. Leukemia inhibitory factor promotes the regeneration of rat uterine horns with full-thickness injury. Wound Repair Regen. 27:477–487, 2019.

    Article  PubMed  Google Scholar 

  221. Yamauchi, N., O. Yamada, T. Takahashi, K. Imai, T. Sato, A. Ito, and K. Hashizume. A three-dimensional cell culture model for bovine endometrium: regeneration of a multicellular spheroid using ascorbate. Placenta. 24:258–269, 2003.

    Article  CAS  PubMed  Google Scholar 

  222. Yao, A., M. J. Ingargiola, C. D. Lopez, P. Sanati-Mehrizy, N. M. Burish, E. M. Jablonka, and P. J. Taub. Total penile reconstruction: a systematic review. J. Plastic Reconstr. Aesthet. Surg. 71:788–806, 2018.

    Article  CAS  Google Scholar 

  223. Yao, Q., Y.-W. Zheng, H.-L. Lin, Q.-H. Lan, Z.-W. Huang, L.-F. Wang, R. Chen, J. Xiao, L. Kou, H.-L. Xu, and Y.-Z. Zhao. Exploiting crosslinked decellularized matrix to achieve uterus regeneration and construction. Artif. Cells Nanomed. Biotechnol. 48:218–229, 2020.

    Article  CAS  PubMed  Google Scholar 

  224. Ying, Q.-L., J. Wray, J. Nichols, L. Batlle-Morera, B. Doble, J. Woodgett, P. Cohen, and A. Smith. The ground state of embryonic stem cell self-renewal. Nature. 453:519–523, 2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Yoo, J. J., I. Lee, and A. Atala. Cartilage rods as a potential material for penile reconstruction. J. Urol. 160:1164–1168, 1998.

    Article  CAS  PubMed  Google Scholar 

  226. Yoo, J. J., H. J. Park, I. Lee, and A. Atala. Autologous engineered cartilage rods for penile reconstruction. J. Urol. 162:1119–1121, 1999.

    Article  CAS  PubMed  Google Scholar 

  227. Yoon, H.-J., Y. J. Lee, S. Baek, Y. S. Chung, D.-H. Kim, J. H. Lee, Y. C. Shin, Y. M. Shin, C. Ryu, H.-S. Kim, S. H. Ahn, H. Kim, Y. BinWon, I. Lee, M. J. Jeon, S. H. Cho, B. S. Lee, H.-J. Sung, and Y. S. Choi. Hormone autocrination by vascularized hydrogel delivery of ovary spheroids to rescue ovarian dysfunctions. Sci. Adv. 7:eabe8873, 2021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Yoon, S. Y., J. A. Yoon, M. Park, E.-Y. Shin, S. Jung, J. E. Lee, J. H. Eum, H. Song, D. R. Lee, W. S. Lee, and S. W. Lyu. Recovery of ovarian function by human embryonic stem cell-derived mesenchymal stem cells in cisplatin-induced premature ovarian failure in mice. Stem Cell Res. Ther. 11:255, 2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Yoshimasa, Y., and T. Maruyama. Bioengineering of the uterus. Reprod. Sci. 28:1596–1611, 2021.

    Article  PubMed  Google Scholar 

  230. Young, R. C., and G. Goloman. Allo- and xeno-reassembly of human and rat myometrium from cells and scaffolds. Tissue Eng. Part A. 19:2112–2119, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Yu, B., E. B. Nguyen, S. McCartney, S. Strenk, D. Valint, C. Liu, C. Haggerty, and D. N. Fredricks. Vaginal bacteria elicit acute inflammatory response in fallopian tube organoids: a model for pelvic inflammatory disease. bioRxiv. 2023. https://doi.org/10.1101/2023.02.06.527402.

    Article  PubMed  PubMed Central  Google Scholar 

  232. Yucer, N., M. Holzapfel, T. Jenkins Vogel, L. Lenaeus, L. Ornelas, A. Laury, D. Sareen, R. Barrett, B. Y. Karlan, and C. N. Svendsen. Directed differentiation of human induced pluripotent stem cells into fallopian tube epithelium. Sci. Rep. 7:10741–43, 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  233. Zhang, H., M. Albersen, X. Jin, and G. Lin. Stem cells: novel players in the treatment of erectile dysfunction. Asian J. Androl. 14:145–155, 2012.

    Article  PubMed  Google Scholar 

  234. Zhang, J., R. Du, L. Zhang, Y. Li, M. Zhang, S. Zhao, X. Huang, and Y. Xu. A new material for tissue engineered vagina reconstruction: acellular porcine vagina matrix. J. Biomed. Mater. Res. A. 105:1949–1959, 2017.

    Article  CAS  PubMed  Google Scholar 

  235. Zhang, J., J. Hatakeyama, K. Eto, and S. Abe. Reconstruction of a seminiferous tubule-like structure in a 3 dimensional culture system of re-aggregated mouse neonatal testicular cells within a collagen matrix. Gen. Comp. Endocrinol. 205:121–132, 2014.

    Article  CAS  PubMed  Google Scholar 

  236. Zhang, Y., Z. Zhu, K. Hua, L. Yao, Y. Liu, and J. Ding. Umbilical cord-derived mesenchymal stem cell transplantation in vaginal replacement in vitro and in a rat model. Am. J. Transl. Res. 10:3762–3772, 2018.

    CAS  PubMed  PubMed Central  Google Scholar 

  237. Zhao, C., Z. Wang, C. Hua, J. Ji, Z. Zhou, Y. Fang, D. Weng, L. Lu, Y. Pang, and W. Sun. Design, modeling and 3D printing of a personalized cervix tissue implant with protein release function. Biomed. Mater. 15:45005, 2020.

    Article  CAS  Google Scholar 

  238. Zhao, G., Y. Cao, X. Zhu, X. Tang, L. Ding, H. Sun, J. Li, X. Li, C. Dai, T. Ru, H. Zhu, J. Lu, C. Lin, J. Wang, G. Yan, H. Wang, L. Wang, Y. Dai, B. Wang, R. Li, J. Dai, Y. Zhou, and Y. Hu. Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman’s syndrome. Sci. China Life Sci. 60:404–416, 2017.

    Article  CAS  PubMed  Google Scholar 

  239. Zhao, Y., S. Chen, P. Su, F. Huang, Y. Shi, Q. Shi, and S. Lin. Using mesenchymal stem cells to treat female infertility: an update on female reproductive diseases. Stem Cells Int. 2019:9071720, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  240. Zhu, L., H. Zhou, Z. Sun, W. Lou, and J. Lang. Anatomic and sexual outcomes after vaginoplasty using tissue engineered biomaterial graft in patients with Mayer–Rokitansky–Küster–Hauser syndrome: a new minimally invasive and effective surgery. J. Sex Med. 10:1652–1658, 2013.

    Article  PubMed  Google Scholar 

  241. Zoloth, L. Ethical issues. In: Principles of Tissue Engineering, edited by R. Lanza, R. Langer, J. P. Vacanti, and A. B. T.-P. of T. E. Fifth E. Atala. Academic Press, 2020, pp. 1585–1591. https://doi.org/10.1016/B978-0-12-818422-6.00088-5

  242. Campbell, G. R., G. Turnbull, L. Xiang, M. Haines, S. Armstrong, B. E. Rolfe, and J. H. Campbell. The peritoneal cavity as a bioreactor for tissue engineering visceral organs: bladder uterus and vas deferens. J Tissue Eng Regen Med. 2:50–60, 2008.

  243. Zuk, A. K., X. Wen, S. Dilworth, D. Li, and L. Ghali. Modeling and validating three dimensional human normal cervix and cervical cancer tissues in vitro. J Biomed Res. 31:240–247, 2017.

  244. De Gregorio V., G. Imparato , F. Urciuolo, and P. A. Netti. 3D stromal tissue equivalent affects intestinal epithelium morphogenesis in vitro. Biotechnol Bioeng. 115:1062–1075, 2018.

  245. Park, D. W., D. S. Choi, H. S. Ryu, H. C. Kwon, H. Joo, and C. K. Min. A well-defined in vitro three-dimensional culture of human endometrium and its applicability to endometrial cancer invasion. Cancer Lett. 195:185–192, 2003.

  246. Liu, H. C., Z. He, C. L. Chen, and Z. Rosenwaks. Ability of three-dimensional (3D) engineered endometrial tissue to support mouse gastrulation in vitro. Fertil Steril. 80:78, 2003.

    Article  Google Scholar 

  247. Young. R. C., R. Schumann, and P. Zhang. Three-dimensional culture of human uterine smooth muscle myocytes on a resorbable scaffolding. Tissue Eng. 9:451–459, 2003.

  248. Lü S. H., H. B. Wang, H. Liu, H. P. Wang, Q. X. Lin, D. X. Li, Y. X. Song, C. M. Duan, L. X. Feng, and C. Y. Wang. Reconstruction of engineered uterine tissues containing smooth muscle layer in collagen/matrigel scaffold in vitro. Tissue Eng Part A. 15:1611–1618, 2009.

  249. MacKintosh S. B., L. P. Serino, P. D. Iddon, R. Brown, R. S. Conlan, C. J. Wright, T. G. Maffeis, M. J. Raxworthy, and I. M. Sheldon. A three-dimensional model of primary bovine endometrium using an electrospun scaffold. Biofabrication. 7:025010, 2015.

  250. Cook C. D., A. S. Hill, M. Guo, L. Stockdale, J. P. Papps, K. B. Isaacson, D. A. Lauffenburger, and L. G. Griffith. Local remodeling of synthetic extracellular matrix microenvironments by co-cultured endometrial epithelial and stromal cells enables long-term dynamic physiological function. Integr Biol. 9:271–289, 2017.

  251. Yang H., S. Wu, R. Feng, J. Huang, L. Liu, F. Liu, and Y. Chen. Vitamin C plus hydrogel facilitates bone marrow stromal cell-mediated endometrium regeneration in rats. Stem Cell Res Ther. 8:267, 2017.

  252. Schuster J., J. Zhang, and M. Longo. A novel human osteoblast-derived severe combined immunodeficiency mouse model of bone metastasis. J Neurosurg Spine. 4:388–391, 2006.

  253. Park H. J., J. J. Yoo, R. T. Kershen, R. Moreland, and A Atala. Reconstitution of human corporal smooth muscle and endothelial cells in vivo. J Urol. 162:1106–1109, 1999.

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Acknowledgements

This work was supported by the Foundation Louvain (Ph.D. scholarship awarded to S.M., as part of a legacy from Mr. Frans Heyes, and Ph.D. scholarship awarded to A.D. as part of a legacy from Mrs. Ilse Schirmer), the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention grant number T.0004.20 awarded to C.A.A., Ph.D. scholarship awarded to H.V.), the Wallonie-Bruxelles International, and the Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa (WBI-CONFAP, grant SUB/2022/566002 awarded to E.C.R.L. and C.A.A.).

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  1. Department of Histology, Embryology and Cell Biology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil

    Ellen C. R. Leonel

  2. Pôle de Recherche en Physiopathologie de la Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Hippocrate 55, bte B1.55.03, 1200, Brussels, Belgium

    Arezoo Dadashzadeh, Saeid Moghassemi, Hanne Vlieghe, Christine Wyns & Christiani A. Amorim

  3. Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

    Christine Wyns

  4. Departamento de Ciencias Químicas y Biológicas, Facultad de Ciencias de la Salud, Universidad Bernardo O’Higgins, Santiago, Chile

    Renan Orellana

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Leonel, E.C.R., Dadashzadeh, A., Moghassemi, S. et al. New Solutions for Old Problems: How Reproductive Tissue Engineering Has Been Revolutionizing Reproductive Medicine. Ann Biomed Eng 51, 2143–2171 (2023). https://doi.org/10.1007/s10439-023-03321-y

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  • DOI: https://doi.org/10.1007/s10439-023-03321-y

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