Evidence map›Paper›PMID 42749206›Full record

ArticleActa biomaterialia2026

Assessing bioactivity and biointegration of engineered salivary tissue constructs in a preclinical unilateral fractionated irradiated rat model.

Kerry P Pernick, Juliana Amorim, Caio C da Silva Barros, Iva Vesela, Meng-Jia Lian, Samuel Nahass, Thaise C Geremias, Warren Swegal, Andrew M Farach, Daniel A Harrington and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta biomaterialia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Kerry P PernickDepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Juliana AmorimDepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Caio C da Silva BarrosDepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Iva VeselaDepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Meng-Jia LianDepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
Samuel NahassDepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Thaise C GeremiasDepartment of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, USA.
Warren SwegalDepartment of Otolaryngology Head and Neck Surgery, Allegheny Health Network, Allegheny General Hospital, Pittsburgh, PA, USA.
Andrew M FarachDepartment of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA.
Daniel A HarringtonDepartment of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, USA.
Danielle WuDepartment of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Bioengineering, Rice University, Houston, TX, USA.
Mary C Farach-CarsonDepartment of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Bioengineering, Rice University, Houston, TX, USA. Electronic address: [email protected].
Isabelle M A LombaertDepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA. Electronic address: [email protected].

Funding

Functional Biointegration of Bioengineered Salivary Tissues in Irradiated Animal ModelsR01DE032364 · NIDCR · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI FARACH-CARSON, MARY C, LOMBAERT, ISABELLE M.A. · 2022 to 2025
$2.8M
NIDCR NIH HHS R01 DE032364
6 · The paper itself

Abstract

Human salivary stem/progenitor cell (hS/PC)-loaded hyaluronic acid (HA)-based hydrogels, termed 3D-salivary tissue constructs (3D-ST), hold great promise as a regenerative platform for repairing radiation-damaged salivary glands. Here, we developed a next-generation 3D-ST using heparin-modified HA and bioactive peptide-modified hydrogels. This formulation provides upcoming opportunities for controlled pre-loading and localized presentation of heparin-binding growth factors prior to surgical implantation to enhance in vivo hS/PC bioactivity. To model clinically relevant radiation injury, we established an athymic rat model subjected to computed tomography (CT)-guided fractionated radiation, resulting in hallmark features of radiation-induced salivary dysfunction. Over 60-days post-irradiation, glands exhibited progressive loss of acini, increased fibrosis, and disruption of endothelial, neuronal, and myoepithelial compartments. Within this injured environment, a surgical pocket was created to precisely implant 3D-STs to assess graft performance. Fluorescent labeling of the 3D-STs enabled post-mortem localization post-implantation. Over 14 days, implanted 3D-STs remained structurally stable within irradiated glands, and hS/PCs remained viable without evidence of local inflammatory responses. Compared to non-injured glands, the irradiated microenvironment suppressed hS/PC proliferation and phenotype, indicating alterations in the irradiated tissue negatively impact hS/PC bioactivity. In addition, host neurovascular migration into the 3D-ST was majorly restricted in irradiated glands, providing opportunities to enhance biointegration. Overall, this work establishes a reproducible preclinical framework for assessing hydrogel biocompatibility and stability, cell bioactivity, and host-graft biointegration prior to scale up into preclinical large animal models. This study has established a tractable approach for improving 3D-ST formulations to enhance hS/PC expansion, differentiation, and future biointegration following implantation into radiation-injured beds. STATEMENT OF SIGNIFICANCE: Our study evaluates the biostability, bioactivity, and biointegration of hydrogel-encapsulated human epithelial stem/progenitors transplanted in healthy versus irradiated parotid gland beds. These findings provide preclinical evidence supporting the translational development of this cell-containing hydrogel for the repair of irradiated glands in patients suffering from xerostomia.

Indexed as

BiointegrationHuman stem/progenitor cellsHydrogelSalivary gland

Identifiers

PMID42749206
PMCPMC13616192

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.