Regenerative Biomaterials
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2025
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IF 8.1
Wang Xinhui,Fan Xiaoju,Zhai Yuanxin,Li Jie,Sun Huilin,Li Jie,Le Hao,Zhang Feng,Zhang Li,Wang Jianhao,Chu Yun,Cui Pengfei
Intrauterine adhesion (IUA) is a prevalent complication arising from uterine surgery, significantly impacting women’s fertility and overall quality of life. The conventional clinical approach involves hysteroscopic separation of uterine adhesions, though this method poses operational challenges and carries risks of postoperative re-adhesion. Alternatively, the intraoperative placement of intrauterine devices or support balloons can act as a physical barrier to prevent adhesion formation. However, its effectiveness is limited and it may result in secondary damage to the endothelial tissue. To tackle these challenges, we have engineered a temperature-responsive hydrogel incorporating Pluronic HP407/HP188 pharmaceutical excipients and recombinant type III collagen (rCol III) as a bioactive element. Upon in situ injection into the uterine cavity, this hydrogel transitions from a sol–gel phase to a gel in response to body temperature changes, thereby minimizing nonspecific distribution and prolonging the duration of treatment. In vitro studies demonstrate that rCol III temperature-responsive hydrogels exhibit favorable biocompatibility, exhibit a recruitment effect on human endometrial stromal cells, suppress the expression of the fibrotic factor transforming growth factor beta 1 and promote angiogenesis. To evaluate its efficacy in preventing IUA via in vivo experiments, we employed sexually mature female rats for IUA modeling and compared its performance with a commercially available product, cross-linked sodium hyaluronate gel. The results indicate that rCol III temperature-responsive hydrogels significantly enhance retention at the injury site, substantially promote endometrial regeneration, augment endometrial blood supply and reduce abnormal fibrin deposition. This study suggests that rCol III temperature-responsive hydrogels can effectively prevent post-surgical uterine adhesions, highlighting their potential as a promising adhesion prevention strategy.
研究领域:
妇科学
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生物材料学
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再生医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Xuemin Liu,Huihui Wang,Jiajie She,Qiang Zhang,Qingyu Hu,Dongdong Li,Hongliang Wu,Xiaofeng Ye,Ruiying Diao,Xuetao Shi,Liping Wang
Intrauterine adhesions (IUA) are a common gynecologic disease worldwide that can lead to menstrual irregularities, infertility, or repeated pregnancy loss. Biomaterials are used as a physical barrier to separate damaged uterine walls and prevent tissue adhesion. However, most biomaterials cannot prevent or even increase inflammation and fibrosis during implantation, which is crucial for IUA development, limiting their application in treatment. To address this, we developed a hydrophilic hydrogel film with a negative surface potential that can absorb excess positive proinflammatory cytokines to alleviate the inflammatory response and limit endometrial fibre formation. In vitro, the hydrogel film exhibits good biocompatibility and anti-fibroblast adhesion properties, and in vivo, they downregulate the expression level of proinflammatory cytokines and reduce the degree of fibrosis. After loading the hydrogel film with vascular endothelial growth factor (VEGF) and implanting it into the injured rat endometrial cavity, the increased local microvessels and higher endometrial thickness indicated improved endometrial regeneration during IUA treatment. In summary, the hydrogel film capable of efficiently reducing inflammation and decreasing fibrosis provides a promising strategy for treating and preventing IUA difficulties, with broad clinical application potential.
研究领域:
妇科学
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生物材料科学
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组织工程
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再生医学
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产品关联
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Ruifang Han,Haiyi Zhou,Xingshan Liang,Siyi He,Xiaoming Sun,Yongge Guan,Yang Song
Endometrium plays a key role in embryo implantation and maintenance of pregnancy. However, to repair endometrial injury is still a challenge. In recent years, hydrogel materials have been widely used as effective support matrices to prevent intrauterine adhesions after endometrial injury. They can also be used as preparation scaffolds for encapsulating MSCs and certain therapeutic drugs. This study aimed to develop a preparation scaffold with high tissue affinity, high viscoelasticity and controlled release for repair of endometrial injury. The scaffold utilized heparin poloxamer (HP) as the matrix material and ε-polylysine (EPL) as the functional excipient to prepare a hydrogel that is suitable for endometrial adhesion and further encapsulate BMSCs. Furthermore, a strategy of the thermo-sensitive EPL-HP hydrogel-encapsulated BMSCs were used for better homing of BMSC after transplantation into the rat endometrial injury model, so as to exert the potential of endometrial regeneration by activating Nrf2 to regulate SDF-1/CXCR4 axis.
研究领域:
生殖医学
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组织工程
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干细胞研究
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Ming Chen,Xuemin Liu,Xiaoxia Song,Xiaofeng Ye,Zeshen Liang,Guoqing Chen,Peixian Cheng,Huihua Yang,Ling Shuai,Dongdong Li,Liping Wang
Thin endometrium (TE), a major cause of embryo implantation failure, increases the risk of early miscarriage, ectopic pregnancy, and perinatal complications. Owing to the poor utilization and short-term effectiveness of current stem cell therapies, their efficacy in improving reproductive outcomes in patients with TE is limited. Endometrial extracellular matrix (EMECM) modified hemispherical hydrogels (ECMHPs) are developed to deliver menstrual blood-derived stem cells (MenSCs) to promote TE repair. The irregular porous structure on one side of the hemispherical hydrogel microspheres significantly enhances their retention capability on the uterine wall, whereas the bioactive decellularized EMECM promotes MenSCs proliferation and paracrine function. In vitro experiments demonstrate that ECMHPs@MenSCs promote the proliferation of damaged human endometrial stromal cells (HESCs) while inhibiting their fibrosis and apoptosis. In TE rat models, intrauterine transplantation of the ECMHPs delivering MenSCs system (ECMHPs@MenSCs) extends retention time, promotes endometrial thickness by 2.3-fold, increases glandular number by 3.7-fold, inhibits endometrial fibrosis. Additionally, this system improves endometrial regeneration markers and uterine receptivity, and restores fertility, with a mean gestational sac number of 11.0 ± 2.8 compared with only 2.3 ± 2.1 in the untreated group. This study provides an efficient and convenient therapeutic strategy for TE repair and fertility restoration.
研究领域:
生殖医学
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组织工程
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干细胞治疗
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生物材料
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再生医学
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妇产科学
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细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Sentao Hu,Yangyang Dai,Liaobing Xin,Xiaowen Zheng,Zi Ye,Songying Zhang,Lie Ma
Intrauterine adhesions (IUA) are the most common cause of uterine infertility, and conventional treatments have not consistently achieved satisfactory pregnancy rates. Stem cell therapy shows promising potential for the clinical treatment of IUA. Although various advanced biomaterials have been designed for delivering stem cells to the uterine cavity, there remain significant challenges, particularly in devising therapeutic strategies for clinical application that minimize surgical incisions and conform to the intricate structure of uterine cavity. Herein, an injectable hydrogel loaded with human umbilical cord-derived mesenchymal stem cells (UCMSCs) was synthesized via the Diels-Alder click reaction for endometrial regeneration and fertility restoration, exhibiting suitable mechanical properties, good biocompatibility, and desirable degradation properties. Notably, this hydrogel permitted minimally invasive administration and integrated seamlessly with surrounding tissue. Our study revealed that the UCMSCs-laden injectable hydrogel enhanced cell proliferation, migration, angiogenesis, and exhibited anti-fibrotic effects in vitro. The implantation of this hydrogel significantly facilitated endometrium regeneration and restored fertility in a rat endometrial damage model. Mechanistically, in vivo results indicated that the UCMSCs-laden injectable hydrogel effectively promoted macrophage recruitment and facilitated M2 phenotype polarization. Collectively, this hydrogel demonstrated efficacy in regenerating damaged endometrium, leading to the restoration of fertility. Consequently, it holds promise as a potential therapeutic strategy for endometrial damage and fertility decline arising from intrauterine adhesions. Statement of significance Severe endometrial traumas frequently lead to intrauterine adhesions and subsequent infertility. Stem cell therapy shows promising potential for the clinical treatment of IUA; however, challenges remain, including low delivery efficiency and compromised stem cell activity during the delivery process. In this study, we fabricated an injectable hydrogel loaded with UCMSCs via the Diels-Alder click reaction, which exhibited unique bioorthogonality. The in situ-gelling hydrogels could be introduced through a minimally invasive procedure and adapt to the intricate anatomy of the uterus. The UCMSCs-laden injectable hydrogel promoted endometrial regeneration and fertility restoration in a rat endometrial damage model, efficaciously augmenting macrophage recruitment and promoting their polarization to the M2 phenotype. The administration of UCMSCs-laden injectable hydrogel presents a promising therapeutic strategy for patients with severe intrauterine adhesion.
研究领域:
生殖医学
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干细胞治疗
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生物材料
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组织工程
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产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2022
·Vol. 47
·期 1
·75-85
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IF 4.473
Yanhua Mao,Yuan Yang,Congcong Sun,Yulong Zou,Yingfeng Zhang,Benyuan Wu,Changjiang Li,Jinglin Huang,Wenwen Zhang,Jia Wang
Human amniotic transplantation has been proposed to improve the therapeutic efficacy of intrauterine adhesions (IUAs). Human amniotic mesenchymal stem stromal cells (hAMSCs) can differentiate into multiple tissue types. This study aimed to investigate the mechanism by which hAMSCs transplantation promotes endometrial regeneration. The rat models with IUA were established through mechanical and infective methods, and PKH26-labeled hAMSCs were transplanted through the tail vein (combined with/without estrogen). Under three different conditions, hAMSCs differentiated into endometrium-like cells. HE and Mason staining assays, and immunohistochemistry were used to compare the changes in rat models treated with hAMSCs and/or estrogen transplantation. To define the induction of hAMSCs to endometrium-like cells in vitro, an induction medium (cytokines, estrogen) was used to investigate the differentiation of hAMSCs into endometrium-like cells. qRT-polymerase chain reaction (PCR) and western blotting were performed to detect the differentiation of hAMSCs into endometrium-like cells. A greater number of glands, fewer endometrial fibrotic areas, and stronger expression of vascular endothelial growth factor and cytokeratin in the combined group (hAMSCs transplantation combined with estrogen) than in the other treatment groups were observed. hAMSCs could be induced into endometrium-like cells by cytokine treatment (TGF-β1, EGF, and PDGF-BB). Transplantation of hAMSCs is an effective alternative for endometrial regeneration after injury in rats. The differentiation protocol for hAMSCs will be useful for further studies on human endometrial regeneration.
研究领域:
生殖医学
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干细胞生物学
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再生医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiangyan Xie,Xue Ao,Ruijuan Xu,Hongyi Lv,Shiqiao Tan,Jinrong Wu,Lijuan Zhao,Yi Wang
The combination of pharmacological and physical barrier therapy is a highly promising strategy for treating intrauterine adhesions (IUAs), but there lacks a suitable scaffold that integrates good injectability, proper mechanical stability and degradability, excellent biocompatibility, and non-toxic, non-rejection therapeutic agents. To address this, a novel injectable, degradable hydrogel composed of poly(ethylene glycol) diacrylate (PEGDA), sodium alginate (SA), and l -serine, and loaded with platelet-rich plasma (PRP) (referred to as PSL-PRP) is developed for treating IUAs. l -Serine induces rapid gelation within 1 min and enhances the mechanical properties of the hydrogel, while degradable SA provides the hydrogel with strength, toughness, and appropriate degradation capabilities. As a result, the hydrogel exhibits an excellent scaffold for sustained release of growth factors in PRP and serves as an effective physical barrier. In vivo testing using a rat model of IUAs demonstrates that in situ injection of the PSL-PRP hydrogel significantly reduces fibrosis and promotes endometrial regeneration, ultimately leading to fertility restoration. The combined advantages make the PSL-PRP hydrogel very promising in IUAs therapy and in preventing adhesions in other internal tissue wounds.
研究领域:
生物材料
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组织工程
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生殖医学
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药剂学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yuxiang Liang,Qizhi Shuai,Xiao Zhang,Shanshan Jin,Yuqian Guo,Zhaowei Yu,Xinrui Xu,Ruifang Ao,Zhiwei Peng,Huimin Lv,Sheng He,Chunfang Wang,Guohua Song,Zhizhen Liu,Hong Zhao,Qilong Feng,Ruochen Du,Bin Zheng,Zhaoyang Chen,Jun Xie
Intrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity-reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC-derived exosomes (DSC-exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal-to-epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC-exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.
研究领域:
再生医学
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生殖生物学
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细胞治疗
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组织工程
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生物信息学
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DOI
PubMed
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 12
·2102220
·
IF 17.521
Chenle Dong,Chen Yang,Muhammad Rizwan Younis,Jing Zhang,Gang He,Xingdi Qiu,Lian-Hua Fu,Dong-Yang Zhang,Hao Wang,Wenli Hong,Jing Lin,Xueqing Wu,Peng Huang
Intrauterine adhesions (IUAs) caused by mechanical damage or infection increase the risk of infertility in women. Although numerous physical barriers such as balloon or hydrogel are developed for the prevention of IUAs, the therapeutic efficacy is barely satisfactory due to limited endometrial healing, which may lead to recurrence. Herein, a second near-infrared (NIR-II) light-responsive shape memory composite based on the combination of cuprorivaite (CaCuSi 4 O 10 ) nanosheets (CUP NSs) as photothermal conversion agents and polymer poly( d , l -lactide- co -trimethylene carbonate) (PT) as shape memory building blocks is developed. The as-prepared CUP/PT composite possesses excellent shape memory performance under NIR-II light, and the improved operational feasibility as an antiadhesion barrier for the treatment of IUAs. Moreover, the released ions (Cu, Si) can stimulate the endometrial regeneration due to the angiogenic bioactivity. This study provides a new strategy to prevent IUA and restore the injured endometrium relied on shape memory composite with enhanced tissues reconstruction ability.
研究领域:
生物医学工程
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材料科学
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生殖医学
✓ 已验证
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2022
·Vol. 13
·期 1
·1-19
·
IF 8.079
Lin Yifeng,Dong Shunni,Ye Xiaohang,Liu Juan,Li Jiaqun,Zhang Yanye,Tu Mixue,Wang Siwen,Ying Yanyun,Chen Ruixue,Wang Feixia,Ni Feida,Chen Jianpeng,Du Binyang,Zhang Dan
Background Thin endometrium is a primary cause of defective endometrial receptivity, resulting in infertility or recurrent miscarriage. Much effort has been devoted toward regenerating thin endometrium by stem cell-based therapies. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs with various advantages. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and possible underlying mechanisms.
Methods Ethanol was injected into the mice uterus to establish the endometrium-injured model. The retention time of HP-MSCs and HA hydrogel was detected by in vivo imaging, while the distribution of HP-MSCs was detected by immunofluorescence staining. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry. In vitro studies were further conducted using EdU, transwell, tube formation, and western blot assays. Results Instilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri than normal HP-MSCs. In vivo studies showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness ( P < 0.001, P < 0.05), decrease fibrous area ( P < 0.0001), and promote the proliferation and angiogenesis of endometrial cells (as indicated by Ki67 and VEGF, P < 0.05, P < 0.05, respectively) in mice injured endometrium. HP-MSCs-HA could also significantly improve the embryo implantation rate ( P < 0.01) compared with the ethanol group. Further mechanistic study showed the paracrine effects of HP-MSCs. They could not only promote the proliferation and migration of human endometrial stromal cells via the JNK/Erk1/2-Stat3-VEGF pathway but also facilitate the proliferation of glandular cells via Jak2-Stat5 and c-Fos-VEGF pathway. In turn, the increased VEGF in the endometrium promoted the angiogenesis of endothelial cells. Conclusion Our study suggested the potential therapeutic effects and the underlying mechanisms of HP-MSCs-HA on treating thin endometrium. HA hydrogel could be a preferable delivery method for HP-MSCs, and the strategy represents a promising therapeutic approach against endometrial injury in clinical settings. Graphical abstract
研究领域:
生殖医学
·
干细胞治疗
·
组织工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Qizhi Shuai,Yuxiang Liang,Xinrui Xu,Zulala Halbiyat,Xiaowan Wang,Jingwen Cheng,Jialing Liu,Tingjuan Huang,Zhiwei Peng,Lei Wang,Sheng He,Hong Zhao,Zhizhen Liu,Jun Xu,Jun Xie
A thinner endometrium has been linked to implantation failure, and various therapeutic strategies have been attempted to improve endometrial regeneration, including the use of mesenchymal stem cells (MSCs). However, low survival and retention rates of transplanted stem cells are main obstacles to efficient stem cell therapy in thin endometrium. Collagen type III is a key component of the extracellular matrix, plays a crucial role in promoting cell proliferation and differentiation, and has been identified as the major collagen expressed at the implantation site. Herein, composite alginate hydrogel containing recombinant type III collagen (rCo III) and umbilical cord mesenchymal stem cells are developed. rCo III serves as favorable bioactive molecule, displaying that rCo III administration promotes MSCs proliferation, stemness maintenance and migration. Moreover, rCo III administration enhances cell viability and migration of mouse endometrial stromal cells (ESCs). In a mouse model of thin endometrium, the Alg-rCo III hydrogel loaded with MSCs (MSC/Alg-rCo III) significantly induces endometrial regeneration and fertility enhancement in vivo. Further studies demonstrate that the MSC/Alg-rCo III hydrogel promoted endometrial function recovery partly by regulating mesenchymal-epithelial transition of ESCs. Taken together, the combination of Alg-rCo III hydrogel and MSCs has shown promising results in promoting endometrium regeneration and fertility restoration, and may provide new therapeutic options for endometrial disease.
研究领域:
生殖生物学
·
干细胞疗法
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组织工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2023
·
IF 17.4
Honglei Zhu,Huayan Li,Kunjie Gao,Yi Huang,Yuru Liao,Weichu Hu,Feng Chen,Haoyuan Jiang,Xiaomei Liang,Haonan Song,Yuxin Wang,Hanrong Huang,Yifan Wang,Fan Liu,Hao Huang,Qian Wang,Xiao Yi
Intrauterine adhesion (IUA) is one of the main causes of female infertility. Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs), are consisted of a complete lipid bilayer structure, rich in multiple factors and miRNAs related to tissue regeneration , which are the main effective paracrine components of MSCs to treat IUA. However, the poor secretion and bioactivity of EVs leading to the unexpected therapeutic efficacy of MSC-EVs, have been obstacles to their widespread use in clinical practice. Here, we developed human chorionic villi (CV)-derived nanofibers that mimic the tissue-specific ECM microenvironment of CV-derived MSCs, maintain the stemness of MSCs for a long time, and are rich in apolipoproteins , HSP90 , ANXA1-A6, etc., which can enhance EV secretion and bioactivity. Then, the CV-nanofiber bionic culture system for mesenchymal stem cells was constructed to achieve large-scale cultivation of MSCs for continuous collection of high-concentration EVs enrichment supernatant. Additionally, EVs obtained by this system were encapsulated with CV-nanofibers to form EVs-ECM aggregate, which can effectively promote endometrium regeneration toward supporting fetal development and live births. Our study provides a new idea for enhancing EV secretion and bioactivity, and a cell-free therapy for treating IUA by EVs, thus promoting the potential of clinical application.
研究领域:
生殖医学
·
干细胞生物学
·
组织工程
·
再生医学
✓ 已验证
DOI
高影响因子
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