Delivery of a Jagged1-PEG-MAL hydrogel with pediatric human bone cells regenerates critically sized craniofacial bone defects
Archana Kamalakar,
Brendan Tobin,
Sundus Kaimari,
M Hope Robinson,
Afra I Toma,
Timothy Cha,
Samir Chihab,
Irica Moriarity,
Surabhi Gautam,
Pallavi Bhattaram,
Shelly Abramowicz,
Hicham Drissi,
Andres Garcia,
Levi Wood,
Steven L Goudy
Affiliations
Archana Kamalakar
Department of Pediatric Otolaryngology, Emory University, Atlanta, United States
Brendan Tobin
Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, United States; School of Chemistry and Biomolecular Engineering, Georgia Tech College of Engineering, Atlanta, United States
Sundus Kaimari
Department of Pediatric Otolaryngology, Emory University, Atlanta, United States; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States
Department of Pediatric Otolaryngology, Emory University, Atlanta, United States
Afra I Toma
Department of Pediatric Otolaryngology, Emory University, Atlanta, United States; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States
Timothy Cha
Department of Pediatric Otolaryngology, Emory University, Atlanta, United States
Samir Chihab
Department of Orthopedics, Emory University, Atlanta, United States
Irica Moriarity
Neuroscience Program in College of Sciences, Georgia Institute of Technology, Atlanta, United States
Surabhi Gautam
Department of Orthopedics, Emory University, Atlanta, United States
Pallavi Bhattaram
Department of Orthopedics, Emory University, Atlanta, United States; The Atlanta Veterans Affairs Medical Center Atlanta, Atlanta, United States
Shelly Abramowicz
Department of Pediatric Otolaryngology, Emory University, Atlanta, United States; Department of Surgery, Division of Oral and Maxillofacial Surgery, Emory University, Atlanta, United States
Department of Orthopedics, Emory University, Atlanta, United States; The Atlanta Veterans Affairs Medical Center Atlanta, Atlanta, United States; Department of Cell Biology, Emory University, Atlanta, United States
Andres Garcia
Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, United States; George W. Woodruff School of Mechanical Engineering, Georgia Tech College of Engineering, Atlanta, United States
Levi Wood
Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, United States; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States; George W. Woodruff School of Mechanical Engineering, Georgia Tech College of Engineering, Atlanta, United States
Current treatments for congenital and acquired craniofacial (CF) bone abnormalities are limited and costly. Conventional methods involve surgical correction, short-term stabilization, and long-term bone grafting, which may include problematic allografts and limited autografts. While bone morphogenetic protein 2 (BMP2) has been used for bone regeneration, it can cause bone overgrowth and life-threatening inflammation. Bone marrow-derived mesenchymal stem cell therapies, though promising, are not Food and Drug Administration approved and are resource intensive. Thus, there is a need for effective, affordable, and less side-effect-prone bone regenerative therapies. Previous research demonstrated that JAGGED1 induces osteoblast commitment in murine cranial neural crest cells through a NOTCH-dependent non-canonical pathway involving JAK2–STAT5. We hypothesize that delivery of JAGGED1 and induction of its downstream NOTCH non-canonical signaling in pediatric human osteoblasts constitutes an effective bone regenerative treatment. Delivering pediatric human bone-derived osteoblast-like cells to an in vivo murine bone loss model of a critically sized cranial defect, we identified that JAGGED1 promotes human pediatric osteoblast commitment and bone formation through p70 S6K phosphorylation. This approach highlights the potential of JAGGED1 and its downstream activators as innovative treatments for pediatric CF bone loss.
