Delivery of a Jagged1-PEG-MAL hydrogel with pediatric human bone cells regenerates critically sized craniofacial bone defects.

Autor:	Kamalakar A; Department of Pediatric Otolaryngology, Emory University, Atlanta, United States., Tobin B; 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., Kaimari S; Department of Pediatric Otolaryngology, Emory University, Atlanta, United States.; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States., Robinson MH; Department of Pediatric Otolaryngology, Emory University, Atlanta, United States., Toma AI; Department of Pediatric Otolaryngology, Emory University, Atlanta, United States.; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States., Cha T; Department of Pediatric Otolaryngology, Emory University, Atlanta, United States., Chihab S; Department of Orthopedics, Emory University, Atlanta, United States., Moriarity I; Neuroscience Program in College of Sciences, Georgia Institute of Technology, Atlanta, United States., Gautam S; Department of Orthopedics, Emory University, Atlanta, United States., Bhattaram P; Department of Orthopedics, Emory University, Atlanta, United States.; The Atlanta Veterans Affairs Medical Center Atlanta, Atlanta, United States., Abramowicz S; Department of Pediatric Otolaryngology, Emory University, Atlanta, United States.; Department of Surgery, Division of Oral and Maxillofacial Surgery, Emory University, Atlanta, United States., Drissi H; 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., Garcia A; 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., Wood L; 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., Goudy SL; Department of Pediatric Otolaryngology, Children's Healthcare of Atlanta, Atlanta, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Oct 14; Vol. 13. Date of Electronic Publication: 2024 Oct 14.
DOI:	10.7554/eLife.92925
Abstrakt:	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. Competing Interests: AK, BT, SK, MR, AT, TC, SC, IM, SG, PB, SA, HD, AG, LW, SG No competing interests declared (© 2024, Kamalakar et al.)
Databáze:	MEDLINE
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