Evidence map›Paper›PMID 41340773›Full record

ArticleJournal of tissue engineering

Mesenchymal stem cells delivered via a bioactive disordered peptide-hydrogel platform modulate early inflammation and enhance skeletal repair in a polytrauma model.

Augustine Mark Saiz, Maryam Rahmati, Tony Daniel Baldini, Aneesh Satish Bhat, Soren David Johnson, Mengyao Liu, Renato Miguel Reyes, Shierly W Fok, Mark A Lee, Thaqif El Khassawna and 5 more

Registry-linked trialAbstract read
In one paragraph

Article in Journal of tissue engineering. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07581613 (A Novel Proline-rich Peptide Hydrogel for Periodontal Regeneration), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT07581613 phase1 / phase2not yet recruitingnot on this map

A Novel Proline-rich Peptide Hydrogel for Periodontal Regeneration: a Multicenter Parallel-arm Randomized Clinical Trial

TypeinterventionalSponsorSiddharth ShanbhagRan2026 to 2030Enrolled40ConditionsPeriodontal Disease, Intrabony Periodontal DefectsArmsHydrogel
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Bone Grafts: Everything You Need to Know.Journal of periodontal research · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Augustine Mark SaizDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Maryam RahmatiDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Tony Daniel BaldiniDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Aneesh Satish BhatDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Soren David JohnsonDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Mengyao LiuDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Renato Miguel ReyesDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Shierly W FokDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Mark A LeeDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Thaqif El KhassawnaExperimental Trauma Surgery, Justus-Liebig University Giessen, Germany.
D C Florian WielandInstitute of Metallic Biomaterials, Helmholtz Zentrum Hereon, Geesthacht, Germany.
André Lopes MarinhoInstitute of Metallic Biomaterials, Helmholtz Zentrum Hereon, Geesthacht, Germany.
Clement BlanchetEuropean Molecular Biology Laboratory EMBL, Hamburg Site, Germany.
J Kent LeachDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, USA.
Håvard Jostein HaugenDepartment of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Norway.ORCID https://orcid.org/0000-0002-6690-7233

Funding

Systemic and local immunomodulation of fracture healing in polytraumaK08AR084594 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Augustine Saiz · 2025 to 2026
$339k
NIAMS NIH HHS K08 AR084594
6 · The paper itself

Abstract

Over 30% of polytrauma patients with bone fractures suffer from impaired healing and nonunion due to persistent systemic inflammation. Existing biologic strategies for bone repair primarily focus on osteogenesis but are not designed to modulate systemic immune dysregulation, limiting their utility in the polytrauma setting. To overcome this, we developed a hyaluronic acid-based hydrogel (HA) incorporating osteogenic intrinsically disordered peptides (P2) and mesenchymal stem cells (MSCs) to promote bone regeneration and modulate inflammation simultaneously. MSCs entrapped in hydrogels containing P2 (HA + P2) exhibited increased cell viability, alkaline phosphatase activity, and calcium deposition under in vitro polytrauma conditions compared to MSCs in hydrogels alone (HA). We utilized a murine polytrauma model (4 mm femoral osteotomy + blunt chest trauma) in mice. We studied the inflammatory response and bone formation over 21 days in mice treated with (1) HA, (2) HA + P2, or (3) HA + P2 + MSCs. We observed that adding P2 enhanced bone mineralization at the fracture site, yet transplantation of MSCs with P2 further increased mineralization. Both HA + P2 and HA + P2 + MSCs groups attenuated the systemic inflammatory response to near healthy baseline values. The HA + P2 group significantly accelerated the first stages of fracture healing by upregulating genes encoding for collagen biosynthesis, modifying enzymes, and extracellular matrix (ECM)-receptor interaction. Mice treated with HA + P2 + MSCs exhibited transcriptional regulation resulting in the upregulation of key repair genes related to cell cycle control, E2F transcriptional regulation, and TP53-mediated DNA repair, alongside downregulation of inflammatory pathways (IL-2, IL-3, and IL-5 signaling) and improved fracture healing. This study demonstrated that the combination of intrinsically disordered peptides and mesenchymal stem cells in HA-based hydrogels enhances bone formation, modulates both local and systemic inflammation, and improves structural organization at the fracture site in polytrauma conditions.

Indexed as

hyaluronic acidhydrogelinflammationintrinsically disordered peptidespolytrauma

Identifiers

PMID41340773
PMCPMC12669493

What OpenQuestion holds

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Read underepoch 390

Registered trials

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 OpenQuestion graph.