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Table 1 List of biomaterials used for the treatment of ovarian aging

From: Biomaterials and advanced technologies for the evaluation and treatment of ovarian aging

Categories

Author

Year

Materials

Model

Major finding

 

Extracellular vesicles

Bo Sun [145]

2019

BMSC-derived exosomes

Cisplatin-induced POF mouse model

Inhibited the apoptosis of granulosa cell.

 
 

Meiling Yang [147]

2020

BMSC-derived exosomes

Cyclophosphamide-induced POF mouse model

Prevented follicular atresia and GCs apoptosis.

 
 

Zhongkang Li [148]

2021

hUCMSC-derived exosomes

Cyclophosphamide-induced POI mouse model

Reduced cell apoptosis and enhanced proliferation.

 
 

Conghui Liu [149]

2020

hUCMSC-derived exosomes

Busulfan and cyclophosphamide-induced POI mouse model

Improved the fertility of POI mice without adverse effects on the cognitive behavior of their offspring.

 
 

Ziling Yang [150]

2019

hUCMSC-derived exosomes

Busulfan and cyclophosphamide-induced POI mouse model

Restored ovarian function by promoting angiogenesis.

 
 

Chenyue Ding [151]

2020

hUCMSC-derived exosomes

Cyclophosphamide-induced POI mouse model

Reduced ROS levels in the damaged ovary and suppressed SIRT7 expression.

 
 

Jin Zhang [152]

2020

hUCMSC-derived exosomes

Cisplatin-damaged granulosa cells

Promoted resistance to cisplatin-induced granulosa cells apoptosis and restored synthesis and secretion of steroid hormone in granulosa cells.

 
 

Liping Sun [153]

2017

hUCMSC-derived exosomes

Cisplatin-damaged granulosa cells

Ameliorated cisplatin-induced granulosa cells stress and apoptosis in vitro.

 
 

Boxian Huang [155]

2018

hADMSC-derived exosomes

Cyclophosphamide-induced POI mouse model

Inhibited expression of the apoptosis genes in human granulosa cells and improved ovarian function.

 
 

Chenyue Ding [157]

2020

hAMSCs-derived exosomes

Cyclophosphamide-induced POI mouse model

Improved proliferation, inhibited apoptosis, reduced ROS level and decreased the expression of SIRT4 and relative genes in POI hGCs and ovaries.

 
 

Qiuwan Zhang [14]

2019

hAECs-derived exosomes

Busulfan and cyclophosphamide-induced POI mouse model

Increased follicles,inhibited GCs apoptosis and protected the ovarian vasculature from damage in POF mice.

 
 

Guan-Yu Xiao [163]

2016

AFMSCs-derived exosome

Busulfan and cyclophosphamide-induced POF mouse model

Inhibited apoptosis in damaged GCs and prevented ovarian follicles from atresia.

 
 

Eman Thabet [164]

2020

AFMSCs-derived extracellular vesicles

Cyclophosphamide-induced premature ovarian dysfunction rats model

Restored total follicular counts, AMH levels,regular estrous cycles and fruitful conception.

 
 

Siwen Zhang [166]

2021

MenSCs-derived exosomes

4-Vinylcyclohexene diepoxide-induced POI mouse model

Promoted follicular development, restored fertility and improved live birth.

 
 

Chenfeng Yuan [172]

2021

Follicular fluid exosomes

Porcine granulosa cells

Increased the proliferation and progesterone synthesis of porcine ovarian granulosa cells.

 
 

Samuel Gebremedhn [173]

2020

Follicular fluid exosomes

Bovine granulosa cells

Protected against heat stress by reducing the amount of ROS accumulation.

 
 

Thais A Rodrigues [174]

2019

Follicular fluid exosomes

Cultured cumulus—oocyte complex

Increased the resistance of the oocyte to heat shock and improved the cleavage and blastocyst rates.

 

Extracellular matrix

Monica M Laronda [180]

2015

SDS

Ovariectomized mice

It could  significantly change ECM, and had a strong destructive effect on the ultrastructure of natural tissues.

 
 

S E Pors [186]

2019

0.1% SDS and DNA enzymes

Immunodeficient mice

Adequately decellularized both human ovarian medullary and cortical tissue by eliminating all cells and leaving the ECM intact.

 
 

Wen-Yue Liu [187]

2017

Triton X-100 solution and DNA enzyme

Rats

Had no cytotoxicity to rat ovarian cells in vitro and only caused minimal immunogenic response in vivo.

 
 

Maryam Nezhad Sistani [188]

2021

1%Triton X-100 and 0.5%SDS

The endometrial mesenchymal cells

It could  effectively decellularize human ovarian tissue and highly preserve ECM content and non-cytotoxic properties.

 
 

Farideh Eivazkhani [184]

2019

NaOH used as a satisfactory decellularization agent

Ovariectomized mice

It supported  follicular reconstruction better than SDS.

 
 

Ashraf Hassanpour [179]

2018

SLES as an ionic detergent

Ovariectomized rats

Preserved the structure and composition of ovarian ECM, and promoted in vitro and in vivo biocompatibility and neovascularization of biological ovarian scaffides.

 
 

Hossein Nikniaz [190]

2021

Human and bovine acellular ovarian scaffold

Mouse preantral follicles

Sodium alginate containing acellular ovarian scaffold could maintain follicular viability in vitro.

 
 

Sanaz Alaee[191]

2021

Decellularized rat ovarian scaffold

Preantral follicles from prepubertal mice

The preantral follicles transformed into antral follicles, and produced mature meiosis oocytes.

 
 

Wen-Yue Liu[187]

2017

Porcine acellular scaffold

Rat ovarian tissue

Supported the adhesion, migration, and proliferation of immature female rat granulose cells and showed estradiol secretion.

 
 

S E Pors [186]

2019

Acellular human ovarian tissue

Human preantral follicles

Supported the survival of human follicles.

 
 

Eun Jung Kim [192]

2020

ECM-derived hydrogel

Mouse ovarian follicles

Supported follicular morphology and growth, and promoted oocyte maturation.

 
 

Ashraf Hassanpour

[179]

2018

Acellular scaffold of human ovarian tissue

Ovariectomized mice

Increased vaginal opening and estrogen levels after implantation and confirmed the onset of puberty.

 
 

Monica M Laronda [180]

2015

Acellular bovine ovarian scaffold

Ovariectomized mice

Supported the growth of isolated mouse follicles, and produced estrogen and reconstructed menstrual cycles.

 
 

Georgia Pennarossa [193]

2021

Porcine ovarian 3D biological scaffold

Female germ line stem cells

Represented a powerful tool for in vitro recreation of a bioengineered ovary that might constitute a promising solution for hormone and fertility function restoring.

 
 

Kutluk Oktay[194]

2016

Human extracellular tissue matrix scaffold

Human

Pregnancies had  been reported following minimally invasive transplantation of previously cryopreserved ovarian tissue.

 

Collagen

Sunyoung Joo[198]

2016

Collagen-rich, biomimetic 3D shells

Rodent ovarian follicles

Collagen hydrogel properties were  important for follicular phenotype and function maintenance.

 
 

C Torrance [199]

1989

A collagen gel matrix

Mouse preantral follicles

Allowed mouse follicles to separate and grow in vitro for at least 2 weeks.

 
 

G Taru Sharma [200]

2009

A 3D collagen gel culture system

Buffalo preantral follicles

Maintained follicle viability and growth by providing surface interaction and increasing attachment of follicles.

 
 

Kossowska-Tomaszczuk [205]

2010

A three-dimensional culture system containing type I collagen

Immunodeficient mice

Allowed granulosa cell subpopulations isolated from mature follicles to survive and grow, and supported their proliferation into steroid-producing spherical structures.

 
 

Saori Itami [206]

2011

A three-dimensional collagen gel

Mouse preantral follicles

The follicle could maintain its three-dimensional shape, and increase its size in response to FSH stimulation.

 
 

R Abir [201]

1999

collagen gel

Monolayer follicles from human ovarian tissue

Reported an increase in the GC layer and oocyte diameter of human follicles.

 
 

Catherine M H Combelles [202]

2005

3D collagen gel matrix

Cumulus cells

Established for the first time an effective in vitro fertilization combined culture system of human denuded oocytes and cumulus cells.

 
 

L Vanhoutte [213]

2009

Collagen (type I) gel

Dermished foamed oocytes

The fertilization rate of 3D pre-cultured oocytes was significantly higher than that of conventional IVM oocytes.

 
 

Yanjun Yang [214]

2019

The collagen scaffold loaded with hUCMSCs

Cyclophosphamide-induced POF mouse model

Increased the levels of E2 and AMH, ovarian volume and the number of antral follicles.

 
 

Jing Su [154]

2016

The collagen scaffold with ADSCs

Tripterygium Glycosides -induced POF rat model

Increased long-term retention of ADSCs in the ovary and contributed to the restoration of ovarian function.

 
 

Lijun Ding [215]

2018

The collagen scaffold with umbilical cord mesenchymal stem cells

Infertile POF patients

Saved overall ovarian function and leaded to a successful clinical pregnancy.

 

Hyaluronic acid

Nina Desai [219]

2012

A tyramine-based HA hydrogel

Mouse preantral follicles

Promoted the secretion of estradiol and increased the survival rate, GV rupture rate and MII formation rate of cultured follicles.

 
 

I R Brito [220]

2016

A novel hyaluronic acid hydrogel based on tyramine-substituted sodium hyaluronate dihydroxyphenyl bond

Goat preantral follicles

Failed to maintain survival and improve antral formation.

 
 

Parisa Jamalzaei [222]

2020

A HAA composed of HA and ALG

Mouse preantral follicles

Promoted the development of preantral follicles and oocyte maturation in mice and enhanced estrogen secretion.

 
 

L M G Paim [224]

2015

A  vitrification solution with 1% hyaluronic acid

The cumulus oocyte complex

Improved the meiotic recovery rate and nuclear maturation rate of norvegicus oocytes.

 
 

Somayeh Tavana [225]

2016

The HABH

Ovariectomized rats

Prevented or reduced early ischemia-induced follicular loss, promoted follicular survival and angiogenesis.

 
 

Maryam Akhavan Taheri [226]

2016

HA hydrogel

Ovariectomized rats

Had no negative effect on estrus cycle recovery and ovarian preservation,and improved the outcome of autologous transplantation.

 
 

Or Friedman [227]

2012

HA—rich biogel

Immunodeficient mice

Improved ovarian graft survival.

 
 

Wenlin Jiao [228]

2022

A combination of UCMSCs and HA gel

4-Vinylcyclohexene diepoxide -induced POI mouse model

Improved follicular survival.

 
 

Eun-Young Shin [229]

2021

HA gel scaffolder

Cisplatin-induced POI mouse model

Restored the ovarian structure and function and improved the quality of oocyte and embryo as well as the regularity of estrus cycle.

 
 

Guangfeng Zhao [230]

2015

HA

Immunosuppressive drug-induced POI-like rat model

Prevented chemotherapy-induced ovarian damage.

 

Fibrin

Seyedeh Zeynab Sadr [235]

2018

Fibrinalginate scaffold

Mouse preluminal follicles

Improved follicular development and survival, and produced mature oocytes.

 
 

Shi Ying Jin [240]

2010

A fibrinalginate hydrogel matrix

Mouse secondary follicles

Supported the growth of secondary follicles to the antral follicles stage and produced mature oocytes.

 
 

Ariella Shikanov [239, 241]

2011

2009

The FA-IPN

Mouse secondary follicles

Contributed to increased meiosis maturation rates of oocytes.

 
 

I R Brito [220]

2016

Fibrinalginate

Goat preluminal follicles

Restored oocyte meiosis and promoted oocyte maturation to produce parthenotes.

 
 

J Xu [242]

2011

A fibrin alginate matrix

Rhesus monkey secondary follicles

Supported the growth of secondary follicles to antral follicles stage, and promoted the maturation of oocytes to MII stage.

 
 

J Xu [243]

2013

Fibrinin-sodium alginate 3D capsule

Primate rhesus monkey primary follicles

Primate oocytes derived from primary follicles developed in vitro had  the ability to restart meiosis for fertilization.

 
 

Alireza Rajabzadeh [245]

2020

A fibrin hydrogel scaffold supplemented with platelet lysates

Mouse preantral follicles

Improved the local vascularization of follicles, and the survival rate of follicles, and promoted the growth of follicles to the stage of antral follicles.

 
 

Valérie Luyckx [246]

2014

A fibrin matrix containing low concentrations of fibrinogen and thrombin

Mouse preantral follicles and ovarian cells

All follicles were found to be alive or only slightly damaged and to grow to the antral follicular stage.

 
 

M C Chiti [247]

2016

Fibrinogen and thrombin (F12.5/T1) substrates

SCID mice

Isolated secondary follicles survived and grew to the antral follicle stage.

 
 

Rachel M Smith [248]

2014

Fibrin hydrogel

Infertile mouse model

Restored ovarian endocrine function.

 
 

Fernanda Paulini [249]

2016

A fibrin matrix containing fibrinogen and thrombin

Nude mice

Isolated human follicles were viable after encapsulation in fibrin clots and short-term xenotransplantation.

 
 

Ariella Shikanov [244]

2011

Heparin modified fibrin

Infertile mouse model

Reduced ischemia and improved vascular remodeling.

 
 

Jiang-Man Gao[250]

2013

Fibrin hydrogels mixed

Adult female mice

Increased follicular survival and improved revascularization.

 
 

Chungmo Yang [251]

2021

Fibrin hydrogel containing NO-NPs

Ovariectomized mice

Improved the total number and quality of follicles, induced angiogenesis, and prevented ischemic injury.

 
 

Elham Shojafar [252]

2019

Platelette-rich fibrin biofolders

Ovariectomized mice

Reduced oxidative stress, promoted revascularization, and protected follicular cisterns from ischemia–reperfusion injury.

 
 

Maria Costanza Chiti [237]

2018

A novel fibrin matrix

Human ovarian follicles

Fibrin matrix composed of F50/T50 most closely resembled human ovarian cortex.

 
 

Valérie Luyckx [238]

2013

A artificial ovary  composed of fibrinogen and thrombin

Human ovarian cells

Enabled the survival and proliferation of isolated human ovarian stromal cells.

 

Alginate

Hudson H V Correia [259]

2020

A sodium alginate 3D culture system

Goat primordia follicles

Showed appropriate survival rate, high follicular activation rate and continued to grow throughout culture.

 
 

Samaneh Sadeghnia [261]

2016

A sodium alginate three-dimensional culture system

Sheep primordial/primary follicles

2% sodium alginate supported follicle growth better than 1% sodium alginate.

 
 

Min Xu [262]

2006

An alginate hydrogel matrix

Pseudopregnant female mice

Produced healthy and fertile progenies.

 
 

Jing Xu [263]

2010

Alginate

Rhesus monkey secondary follicles

Grew to the antral follicle stage, produced steroids and growth factors, and produced healthy oocytes within 40 days.

 
 

Min Xu [264]

2009

Alginate

Rhesus monkey secondary follicles

The follicles survived and continued to grow.

 
 

Alon Kedem [266]

2011

Macropores sodium alginate scaffold

Human ovarian cortex slices

There was an increase in developing follicle culture and a decrease in atretic follicles.

 
 

Monica M Laronda [267]

2014

Sodium alginate hydrogel

Human ovarian cortex containing primordial follicles

The ovarian cortex grew, survived, and supported follicular development for up to 6 weeks.

 
 

Christiani A Amorim [268]

2009

alginate matrix

Small human preantral follicles

Survived in vitro culture in alginate matrix for 7 days.

 
 

Antonella Mastrorocco[269]

2021

Alginate microspheres

Lamb cumulus oocyte complexes

Increased the nuclear maturation rate of preadolescent oocytes and reduced the incidence of chromosome abnormality.

 
 

Parisa Jamalzaei [270]

2020

ALG hydrogel

Mouse preantral follicles

Survival rate of 0.5%ALG cultured follicles was significantly higher than 0.75% and 1%ALG cultured follicles.

 
 

Cyrus Jalili [271]

2020

Sodium alginate

Mouse preantral follicles

0.5% alginate was the most favorable concentration.

 
 

Erin R West[258]

2007

Alginate gel

Mouse secondary oocytes

Reducing alginate matrix hardness could maintain intercellular tension homeostasis, promote cell process, create local paracrine environment and improve oocyte quality.

 
 

Julie Vanacker [273]

2014

Alginate saline gel

Immunodeficient mice

Promoted follicular development and vascularization.

 
 

Sivanandane Sittadjody [274]

2017

Sr++ cross-linked alginate

Ovariectorized rats

Achieved stable hormone secretion and improved the adverse effects of hormone deficiency.

 
 

Shani Felder [275]

2019

Macrofenate scaffold

Ovariectorized mice

Showed high serum hormone levels and the appearance of the vaginal area.

 

Sythetic biomaterials

Jiwon Kim [276]

2016

A synthetic hydrogel, PEG-VS

Ovariectorized mice

It was  found to wrap immature follicles successfully functioned as an artificial ovarian tissue in vivo for 60 days.

 
 

Uziel Mendez [277]

2018

A three-dimensional PEG-based culture system

Mice follicles

Improved the survival and maturation rates of small follicles.

 
 

Zhonghua Shi [278]

2021

A supramolecular hydrogel

Aged mice

Delayed ovarian aging in aged mice,stimulated ovaries to secrete estrogen and progesterone, and developed more antral follicles for reproduction.

 
 

Anu David [279]

2017

A TheraCyte device

Ovariectomized mice

Restored follicular development and ovarian endocrine function and reduced FSH levels.

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