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| Title |
Hydrogels Derived from Salivary Gland Extracellular Matrix (ECM) Promote Tissue-Specific Cell Recruitment and Repair in a Rat Salivary Gland Injury Model |
| Clinical Question |
Can a porcine submandibular gland–derived decellularized ECM hydrogel (pDSMG-gel) promote tissue-specific regeneration (rebuilding of acinar/ductal structures and suppression of fibrosis) in an acutely injured rat submandibular gland model? |
| Clinical Bottom Line |
Injection of pDSMG-gel into surgically created rat submandibular gland defects markedly improved histologic regeneration (reappearance of acinar- and ductal-like structures) and substantially suppressed fibrosis compared with untreated defects and collagen I hydrogel controls. The hydrogel preserves tissue-specific ECM components (including laminin, fibronectin and multiple matrisomal proteins), promotes migration/recruitment of endogenous salivary gland (SG) cells in vivo, and activates PI3K/AKT signaling in SG mesenchymal stem cells (MSCs) in vitro. The study does not report direct in-vivo functional saliva output measurements (saliva flow or secretion), but functional restoration is inferred from structural/marker recovery rather than measured secretion. |
| Best Evidence |
(you may view more info by clicking on the PubMed ID link) |
| PubMed ID |
Author / Year |
Patient Group |
Study type
(level of evidence) |
| #1) 37557943 | Wang et al.,2023 | Sprague-Dawley rats, N=20 | In Vivo Animal Study | | Key results | In a combined in vitro and in vivo preclinical study, 6-8 week old Sprague-Dawley rats were assigned to 5 groups: Sham, Defective, 0.5% Col I, 0.5% pDSMG, 1% pDSG.
The study prepared pDSMG hydrogels that retained collagen and GAG content and formed thermoresponsive 0.5% and 1% gels with porous nanofibrous structure and rheological properties similar to collagen I. Proteomic analysis identified ~200 ECM/matrisomal proteins, including collagens, laminins, fibronectin, and secreted factors, with pathway enrichment for ECM–receptor interaction, focal adhesion, and PI3K/AKT signaling. In vitro, primary rat SG MSC-like cells cultured in pDSMG-gel exhibited high viability, increased proliferation, enhanced migration, and early transcriptomic activation of chemokines, with PI3K/AKT involvement confirmed by p-AKT/RAC1 upregulation and inhibition by LY294002. In a rat defect model, pDSMG (especially 1%) promoted reformation of acinar- and duct-like structures and increased AQP5 and CK7/CK18 expression while markedly reducing fibrosis relative to untreated and collagen I controls. Both concentrations were effective, though degradation kinetics were not fully characterized, and no direct saliva flow or secretion measurements were performed, so functional recovery was inferred from structural and molecular outcomes. | |
| Evidence Search |
("Salivary Glands"[Mesh] AND "Extracellular Matrix"[Mesh]) AND ("Hydrogels" OR "Regeneration") AND ("Rats" OR "In Vivo")
|
Comments on
The Evidence |
The results of this study appear reliable, supported by multiple complementary analyses including hydrogel characterization, proteomics, in vitro mechanistic assays, and in vivo histology and immunofluorescence. Appropriate control groups (defect-only and collagen I gel) were included to assess the specific effects of pDSMG-gel. Sample sizes (n=4 per group, total 20 rats) allowed for statistical comparisons across histologic and molecular outcomes. The use of naturally derived, tissue-specific decellularized ECM, without the addition of drugs or stem cells, further strengthens the potential utility of the hydrogel in real-life therapeutic scenarios. However, limitations of the study include the use of a small animal model and a short follow-up time. Moreover, the rat model raises uncertainty about the potential translatability of the results to humans. Additionally, the 4 week follow up period leaves some uncertainty regarding the durability of the regenerated tissue. |
| Applicability |
The study's findings suggest that this tissue specific hydrogel might be a clinically viable treatment for xerostomia. The minimally invasive injection process and cell-free approach present an attractive alternative to stem cell transplantation. However, additional preclinical trials are needed since the potential for immune rejection of a non-human sourced ECM hydrogel remains an area of concern. |
| Specialty/Discipline |
(Oral Medicine/Pathology/Radiology) (General Dentistry) |
| Keywords |
Xerostomia, extracellular matrix, salivary gland, hydrogel, regeneration, PI3K/AKT, stem cell recruitment
|
| ID# |
3597 |
| Date of submission: |
01/21/2026 |
| E-mail |
abdulazees@uthscsa.edu |
| Author |
Parveez Ahamed Abdul Azees |
| Co-author(s) |
Dondrae Carter, Parveez Ahmad Abdul-Azees, Gloria Aboyade, Jerry Chen, David D. Dean, Chih-Ko Yeh, and Xiao-Dong Chen |
| Co-author(s) e-mail |
Dondrae.Carter@my.utsa.edu, abdulazees@uthscsa.edu, gloriaaboyade@gmail.com, chenj14@uthscsa.edu, DeanD@uthscsa.edu, YEH@uthscsa.edu, chenx4@uthscsa.edu |
| Faculty mentor/Co-author |
Xiao-Dong Chen |
| Faculty mentor/Co-author e-mail |
chenx4@uthscsa.edu |
Basic Science Rationale
(Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?) |
post a rationale |
| None available | |
|
Comments and Evidence-Based Updates on the CAT
(FOR PRACTICING DENTISTS', FACULTY, RESIDENTS and/or STUDENTS COMMENTS ON PUBLISHED CATs) |
post a comment |
| None available | |
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