Evidence map›Paper›PMID 25228401›Full record

ArticleTissue engineering. Part A2015

Dual-phase osteogenic and vasculogenic engineered tissue for bone formation.

Rameshwar R Rao, Marina L Vigen, Alexis W Peterson, David J Caldwell, Andrew J Putnam, Jan P Stegemann

Open access · greenAbstract read
In one paragraph

Article in Tissue engineering. Part A, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 19% of its field
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

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Developing anFrontiers in immunology · 2025
    Article
  3. Review
  4. Article
  5. Fabrication and characterization of osteogenic function of progenitor cell-laden gelatin microcarriers.Journal of biomedical materials research. Part B, Applied biomaterials · 2022
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. 3D human bone marrow stromal and endothelial cell spheres promote bone healing in an osteogenic niche.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
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

6 authors at 1 institution in 1 country.

Rameshwar R RaoDepartment of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan.
Marina L Vigen
Alexis W Peterson
David J Caldwell
Andrew J Putnam
Jan P Stegemann
University of Michigan–Ann Arbor · US

Funding

University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
Regulation and Enhancement of Angiogenesis in Dense Fibrin MatricesR01HL085339 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTNAM, ANDREW J · 2007 to 2024
$5.4M
Bone Regeneration Using Osteogenic and Vasculogenic Tissue ModulesR01AR062636 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI STEGEMANN, JAN P. · 2014 to 2018
$1.7M
Preformed vascular modules designed for inosculation with host tissueR01HL118259 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTNAM, ANDREW J, STEGEMANN, JAN P. · 2013 to 2016
$1.5M
Modular Assembly of Interdigitated Osteochondral InterfacesR21AR062709 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI STEGEMANN, JAN P. · 2013 to 2014
$343k
NHLBI NIH HHS R01 HL085339NHLBI NIH HHS R01-HL085339NHLBI NIH HHS R01 HL118259NHLBI NIH HHS R01-HL118259NIAMS NIH HHS R01 AR062636NIAMS NIH HHS R01-AR062636NIAMS NIH HHS R21-AR062709NIGMS NIH HHS T32 GM007266
6 · The paper itself

Abstract

Minimally invasive, injectable bone tissue engineering therapies offer the potential to facilitate orthopedic repair procedures, including in indications where enhanced bone regeneration is needed for complete healing. In this study, we developed a dual-phase tissue construct consisting of osteogenic (Osteo) and vasculogenic (Vasculo) components. A modular tissue engineering approach was used to create collagen/fibrin/hydroxyapatite (COL/FIB/HA) hydrogel microbeads containing embedded human bone marrow-derived mesenchymal stem cells (bmMSC). These microbeads were predifferentiated toward the osteogenic lineage in vitro for 14 days, and they were then embedded within a COL/FIB vasculogenic phase containing a coculture of undifferentiated bmMSC and human umbilical vein endothelial cells (HUVEC). In vitro studies demonstrated homogenous dispersion of microbeads within the outer phase, with endothelial network formation around the microbeads over 14 days in the coculture conditions. Subcutaneous injection into immunodeficient mice was used to investigate the ability of dual-phase (Osteo+Vasculo) and control (Osteo, Vasculo, Blank) constructs to form neovasculature and ectopic bone. Laser Doppler imaging demonstrated blood perfusion through all constructs at 1, 4, and 8 weeks postimplantation. Histological quantification of total vessel density showed no significant differences between the conditions. Microcomputed tomography indicated significantly higher ectopic bone volume (BV) in the Osteo condition at 4 weeks. At 8 weeks both the Osteo and Blank groups exhibited higher BV compared to the Vasculo and dual Osteo+Vasculo groups. These data not only show that osteogenic microbeads can be used to induce ectopic bone formation, but also suggest an inhibitory effect on BV when undifferentiated bmMSC and HUVEC were included in dual-phase constructs. This work may lead to improved methods for engineering vascularized bone tissue, and to injectable therapies for the treatment of orthopedic pathologies in which bone regeneration is delayed or prevented.

Indexed as

Bone DevelopmentCell CommunicationCell DifferentiationCell ProliferationCells, CulturedCoculture TechniquesEndothelial CellsHumansMesenchymal Stem CellsMesenchymal Stem Cell TransplantationNeovascularization, PhysiologicOsteogenesisTissue Engineering

Identifiers

PMID25228401
PMCPMC4333512
OpenAlexW2324506750

What OpenQuestion 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 OpenQuestion graph.