Enhanced Preprints

Delivery of A Jagged1-PEG-MAL hydrogel with Pediatric Human Bone Cells Regenerates Critically-Sized Craniofacial Bone Defects

  1. Archana Kamalakar
  2. Brendan Tobin
  3. Sundus Kaimari
  4. Afra I. Toma
  5. Irica Moriarity
  6. Surabhi Gautam
  7. Pallavi Bhattaram
  8. Shelly Abramowicz
  9. Hicham Drissi
  10. Andrés J. García
  11. Levi B. Wood
  12. Steven L. Goudy author has email address
  1. Department of Pediatric Otolaryngology, Emory University, Atlanta, GA, USA
  2. Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
  3. School of Chemistry and Biomolecular Engineering, Georgia Tech College of Engineering, Atlanta, GA, USA
  4. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
  5. Neuroscience Program in College of Sciences, Georgia Institute of Technology, Atlanta, GA, USA
  6. Department of Orthopaedics, Emory University, Atlanta, GA, USA
  7. The Atlanta Veterans Affairs Medical Center Atlanta, GA, USA
  8. Department of Surgery, Division of Oral and Maxillofacial Surgery, Emory University, Atlanta, GA, USA
  9. Department of Cell biology, Emory University, Atlanta, GA, USA
  10. George W. Woodruff School of Mechanical Engineering, Georgia Tech College of Engineering, Atlanta, GA, USA
  11. Department of Pediatric Otolaryngology, Children’s Healthcare of Atlanta, Atlanta, GA, USA

Editors

  • Reviewing Editor
    Yousef Abu-Amer
    Washington University in St. Louis, St Louis, United States of America
  • Senior Editor
    Detlef Weigel
    Max Planck Institute for Biology Tübingen, Tübingen, Germany

Reviewer #1 (Public Review):

Summary:

In this manuscript, the authors introduced a compelling study that explored an innovative regenerative treatment for pediatric craniofacial bone loss, with a particular focus on investigating the impacts of JAGGED1 (JAG1) signaling.

Strengths:

Building on their prior research involving the effect of JAG1 on murine cranial neural crest cells, the authors demonstrated successful bone regeneration in an in vivo murine bone loss model with a critically-sized cranial defect, where they delivered JAG1 with pediatric human bone-derived osteoblast-like cells in the hydrogel. Additionally, their findings unveiled a crucial mechanism wherein JAG1 induces pediatric osteoblast commitment and bone regeneration through the phosphorylation of p70 S6K. This discovery offers a promising avenue for potential treatment, involving targeted delivery of JAG1 and activation of downstream p70 s6K, for pediatric craniofacial bone loss. Overall, the experimental design is appropriate, and the results are clearly presented.

Weaknesses:

Several methodology details need to be clearly included and gender differences should be evaluated and discussed.

Reviewer #2 (Public Review):

The current manuscript undoubtedly demonstrates that JAG1 can induce osteogenesis via non-canonical signaling. Using the mouse-calvarial critical defect model, the authors have clearly shown the anabolic regenerative effect of JAG1 via non-canonical pathways. Exploring the molecular mechanisms, the authors have shown that non-canonically JAG1 regulates multiple pathways including STAT5, AKT, P38, JNK, NF-ĸB, and p70 S6K, which together possibly culminate in the activation of p70 S6K. More analysis is required to strongly conclude the role of the JAG1-p70 S6K pathway in the process. In summary, these findings have significant implications for designing new approaches for bone regenerative research.

  1. Howard Hughes Medical Institute
  2. Wellcome Trust
  3. Max-Planck-Gesellschaft
  4. Knut and Alice Wallenberg Foundation