Evidence map›Paper›PMID 34277588›Full record

ArticleFrontiers in bioengineering and biotechnology2021

Robust Angiogenesis and Arteriogenesis in the Skin of Diabetic Mice by Transient Delivery of Engineered VEGF and PDGF-BB Proteins in Fibrin Hydrogels.

Alessandro Certelli, Paolo Valente, Andrea Uccelli, Andrea Grosso, Nunzia Di Maggio, Rosalinda D'Amico, Priscilla S Briquez, Jeffrey A Hubbell, Thomas Wolff, Lorenz Gürke and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in bioengineering and biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

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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

13 authors.

Alessandro CertelliCell and Gene Therapy, Department of Biomedicine, University Hospital of Basel, University of Basel, Basel, Switzerland.
Paolo ValenteCell and Gene Therapy, Department of Biomedicine, University Hospital of Basel, University of Basel, Basel, Switzerland.
Andrea UccelliCell and Gene Therapy, Department of Biomedicine, University Hospital of Basel, University of Basel, Basel, Switzerland.
Andrea GrossoCell and Gene Therapy, Department of Biomedicine, University Hospital of Basel, University of Basel, Basel, Switzerland.
Nunzia Di MaggioCell and Gene Therapy, Department of Biomedicine, University Hospital of Basel, University of Basel, Basel, Switzerland.
Rosalinda D'AmicoCell and Gene Therapy, Department of Biomedicine, University Hospital of Basel, University of Basel, Basel, Switzerland.
Priscilla S BriquezPritzker School of Molecular Engineering, University of Chicago, Chicago, IL, United States.
Jeffrey A HubbellPritzker School of Molecular Engineering, University of Chicago, Chicago, IL, United States.
Thomas WolffVascular Surgery, Department of Surgery, University Hospital of Basel, University of Basel, Basel, Switzerland.
Lorenz GürkeVascular Surgery, Department of Surgery, University Hospital of Basel, University of Basel, Basel, Switzerland.
Edin MujagicVascular Surgery, Department of Surgery, University Hospital of Basel, University of Basel, Basel, Switzerland.
Roberto Gianni-BarreraCell and Gene Therapy, Department of Biomedicine, University Hospital of Basel, University of Basel, Basel, Switzerland.
Andrea BanfiCell and Gene Therapy, Department of Biomedicine, University Hospital of Basel, University of Basel, Basel, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Non-healing ulcers are a serious complication of diabetes mellitus and a major unmet medical need. A major cause for the lack of healing is the impairment of spontaneous vascularization in the skin, despite mostly normal blood flow in deeper large vessels. Therefore, pro-angiogenic treatments are needed to increase therapeutic perfusion by recruiting new arterial connections (therapeutic arteriogenesis). Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis in physiology and disease, but exploitation of its therapeutic potential requires careful control of its dose distribution in tissue. Co-delivery of platelet derived growth factor-BB (PDGF-BB) has been shown to expand the therapeutic window of VEGF and also improve associated arteriogenesis. We used a highly controlled protein delivery system, based on a clinically applicable fibrin-based platform, to investigate the angiogenic and arteriogenic potential of engineered versions (TG-) of VEGF and PDGF-BB proteins in the skin of diabetic and obese db/db mice. Intradermal delivery of therapeutically relevant doses of TG-VEGF and TG-PDGF-BB induced robust growth of new microvascular networks with similar efficacy as in normal littermate control mice. Further, TG-PDGF-BB prevented the formation of aberrant vascular enlargements by high TG-VEGF levels. As fibrin was degraded after the first week, the induced angiogenesis mostly regressed by 4 weeks, but it promoted effective arteriogenesis in the dermal layer. Therefore, controlled co-delivery of TG-VEGF and TG-PDGF-BB recombinant proteins is effective to induce angiogenesis and arteriogenesis in diabetic mouse skin and should be further investigated to promote diabetic wound healing.

Indexed as

angiogenesisarteriogenesisdiabetesfibrinPDGF-BBskinVEGF

Identifiers

PMID34277588
PMCPMC8281302

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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.