Evidence mapPaperPMID 40726570Full record

Review3 Biotech2025

Targeting diabetic foot ulcer pathophysiology: altered signaling pathways and 3D scaffold as an emerging treatment strategy.

S R Chaithra, Salini P Nair, S R Chaithanya, K S Nagashree, Shreya, Karthika Paul, S Vijaya Kumar

Abstract readReview
In one paragraph

Review in 3 Biotech, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

7 authors.

S R ChaithraDepartment of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Sri Shivarathreeshwara Nagar, Mysore, Karnataka 570 015 India.
Salini P NairDepartment of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Sri Shivarathreeshwara Nagar, Mysore, Karnataka 570 015 India.
S R ChaithanyaDepartment of Surgery, Assam Medical College, Dibrugarh, Assam India.
K S NagashreeDepartment of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Sri Shivarathreeshwara Nagar, Mysore, Karnataka 570 015 India.ORCID 0000-0001-8280-6443
ShreyaDepartment of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Sri Shivarathreeshwara Nagar, Mysore, Karnataka 570 015 India.
Karthika PaulDepartment of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka India.
S Vijaya KumarDepartment of Pharmacology, Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, Karnataka India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diabetic wound healing, especially in the context of diabetic foot ulcers, remains a major clinical challenge due to the complex interplay of metabolic, vascular, and cellular dysfunctions caused by chronic hyperglycemia. Impaired healing is driven by weakened inflammatory response, decreased blood vessel formation, reduced collagen production, and impaired fibroblast function. Hyperglycemia activates multiple damaging pathways, including the polyol, protein kinase C, hexosamine, and advanced glycation end-product pathways, which collectively induce oxidative stress and chronic inflammation. In addition, diabetic wounds exhibit impaired responses to hypoxia, marked by reduced expression of hypoxia-inducible factors (HIF-1 and HIF-1α), and elevated phenyl pyruvate, which activate macrophage-driven inflammation through CD36-PPT1-NLRP3 axis. Excessive matrix metalloproteinase (MMP) activity and poor collagen deposition disrupt extracellular matrix remodeling, further compromising tissue repair. Key signaling pathways such as PI3K/Akt, MAPK, TGF-β/SMAD, Notch, NfκB, VEGF, Wnt/β-catenin, and Nrf2 are dysregulated in diabetic wounds, undesirably affecting cell survival, inflammation resolution, and angiogenesis. To overcome these challenges, 3D scaffolds have emerged as an innovative therapeutic approach. Mimicking native ECM, it promotes cell adhesion, proliferation, and differentiation, and also enables controlled delivery of bioactive materials like stem cells, antimicrobials, and growth factors. Fabrication uses advanced materials like hydrogels, nanofibers, and smart polymers; these scaffolds are promising in restoring normal healing dynamics. This review explores the pathophysiology, major dysregulated pathways in DFU, and the evolving role of 3D scaffolds in diabetic wound treatment with supportive evidence of preclinical and clinical studies to improve clinical outcomes and patient's quality of life.

Indexed as

3D scaffoldDiabetes mellitusDiabetic foot ulcerDiabetic woundHyperglycemiaHypoxiaInflammation

Identifiers

PMID40726570
PMCPMC12297080

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.