Injectable antioxidant hyaluronan/chitosan hydrogel as a platelet-rich plasma and stem cell carrier to promote endometrial regeneration and fertility restoration
Abstract
Severe damage to the uterine endometrium can lead to thin endometrium and intrauterine adhesions (IUAs), resulting in infertility or complications during pregnancy. Therapies utilizing mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) represent promising strategies for restoring thin endometrium. However, the low homing rate and functionality of transplanted cells, along with the rapid release of PRP growth factors, limit their therapeutic efficacy. In this study, we developed an in-situ formable and redox-responsive hydrogel composed of thiolated hyaluronan (tHA) and thiolated chitosan (tChi) (tHA-tChi) for encapsulating PRP and mouse adipose-derived stem cells (ADSCs). Our results demonstrate that the tHA-tChi hydrogel exhibits appropriate swelling, injectability, self-healing, and antioxidant properties, alongside a sustained release of PRP growth factors. In vitro experiments indicated that the PRP and ADSCs encapsulated within the hydrogel (ADSCs/tHA-tChi/PRP) stimulated angiogenesis in endothelial cells. In a mouse model of thin endometrium, the ADSCs/tHA-tChi/PRP significantly enhanced endometrial regeneration, as evidenced by increased endometrial thickness and reduced fibrosis. This improvement markedly enhanced endometrial receptivity and pregnancy rates in damaged endometria, correlating with increased angiogenesis and endometrial cell proliferation via activation of the VEGF/AKT/BAD pathway, as shown by Western blotting assays. Overall, the combination…
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The disulfide-crosslinked tChi/tHA hydrogel exhibited rapid sol-gel transition, self-healing, and excellent injectability.
“This disulfide-crosslinked system exhibited favorable properties, including rapid sol–gel transition, self-healing, and excellent injectability.”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [151]
In a rat model of IUA, tChi/tHA hydrogel-treated animals showed significantly improved endometrial regeneration, with greater endometrial thickness, increased gland numbers, and reduced fibrosis compared to untreated controls (p < 0.01).
“In a rat model of IUA, hydrogel-treated animals showed significantly improved endometrial regeneration, with greater endometrial thickness, increased gland numbers, and reduced fibrosis compared to untreated controls (p < 0.01).”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [151]
The tChi/tHA hydrogel demonstrated anti-inflammatory effects by reducing macrophage aggregation and lowering inflammatory marker expression in a hepatic injury model.
“Functionally, the hydrogel demonstrated anti-inflammatory effects by reducing macrophage aggregation and lowering inflammatory marker expression in a hepatic injury model.”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [151]
The tChi/tHA hydrogel has a dual role as both a physical barrier and an active modulator of inflammation, offering a promising strategy for effective adhesion prevention.
“These results highlight the hydrogel’s dual role as both a physical barrier and an active modulator of inflammation, offering a promising strategy for effective adhesion prevention (Figure 8C) [151].”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [151]
A new injectable hydrogel created using thiolated chitosan and thiolated hyaluronic acid is thermosensitive.
“To address the issue of intrauterine adhesion (IUA), a new injectable hydrogel was created using thiolated chitosan (tChi) and thiolated hyaluronic acid (tHA); this hydrogel is thermosensitive, meaning its properties change with temperature, and its development is documented in reference [151].”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [151]
In vivo imaging confirmed prolonged retention of the tChi/tHA hydrogel components in the uterine cavity for up to 14 days.
“In vivo imaging confirmed prolonged retention of the hydrogel components in the uterine cavity for up to 14 days.”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [151]
Cites
Mechanisms and regulation of endothelial VEGF receptor signalling
Simons, M., Gordon, E., & Claesson-Welsh, L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.87 · Cited by 1,498 · see citing works
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Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering
Fazel Anvari-Yazdi, A., Badea, I., & Chen, X. (2025) · Gels · doi:10.3390/gels11060441 · Cited by 20 · see citing works
- Authors
- Zheng, X., Huang, R., Yin, L., Yao, M., Chu, J., Yang, F., Dong, Y., Zhao, M., & Ma, T.
- Affiliations
- Guangdong Medical College (CN)
- Affiliated Hospital of Guangdong Medical College Hospital (CN)
- Corresponding author
- Zhao, Mingyan
- Ma, Tianzhong
- ORCID
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2025-03
- Volume
- 195
- Pages
- 201-215
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W4407027324
- Cited by
- 33
- References
- 1
- Citations by year
- 2026: 21 · 2025: 12
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Guangdong Provincial Natural Science Foundation
- National Natural Science Foundation of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- thiolated chitosan, injectable hydrogel, platelet-rich plasma, adipose-derived stem cells, thin endometrium, endometrial regeneration, fertility restoration, intrauterine adhesions, angiogenesis, redox-responsive hydrogels, sustained growth factor release, endometrial receptivity
- MeSH terms
- Adipose Tissue, Animals, Antioxidants, Endometrium, Female, Fertility, Humans, Hyaluronic Acid, Injections, Regeneration, Stem Cells, Neovascularization, Physiologic, Hydrogels, Chitosan, Mice, Platelet-Rich Plasma, Mesenchymal Stem Cells
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