Involvement of calvarial stem cells in healing: A regional analysis of large cranial defects
Emily L. Durham MA
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorR. Nicole Howie PhD
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorReed Houck BS
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorBrayden Oakes BS
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorZachary Grey MS
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorSarahRose Hall
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorMartin Steed DDS
Department of Oral and Maxillofacial Surgery, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorAmanda LaRue PhD
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina
Ralph H. Johnson VA Medical Center, Charleston, South Carolina
Search for more papers by this authorRobin Muise-Helmericks PhD
Department of Regenerative Medicine and Cellular Biology, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorCorresponding Author
James Cray PhD
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina
Department of Regenerative Medicine and Cellular Biology, Medical University of South Carolina, Charleston, South Carolina
Division of Anatomy, College of Medicine, The Ohio State University, Columbus, Ohio
Reprint requests:
James Cray Jr., Division of Anatomy, College of Medicine, The Ohio State University, 1645 Neil Ave. 279, Hamilton Hall, Columbus, OH 43210.
Tel: 614-292-4831; Fax: 614-292-7659;Email: [email protected]
Search for more papers by this authorEmily L. Durham MA
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorR. Nicole Howie PhD
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorReed Houck BS
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorBrayden Oakes BS
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorZachary Grey MS
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorSarahRose Hall
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorMartin Steed DDS
Department of Oral and Maxillofacial Surgery, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorAmanda LaRue PhD
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina
Ralph H. Johnson VA Medical Center, Charleston, South Carolina
Search for more papers by this authorRobin Muise-Helmericks PhD
Department of Regenerative Medicine and Cellular Biology, Medical University of South Carolina, Charleston, South Carolina
Search for more papers by this authorCorresponding Author
James Cray PhD
Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina
Department of Regenerative Medicine and Cellular Biology, Medical University of South Carolina, Charleston, South Carolina
Division of Anatomy, College of Medicine, The Ohio State University, Columbus, Ohio
Reprint requests:
James Cray Jr., Division of Anatomy, College of Medicine, The Ohio State University, 1645 Neil Ave. 279, Hamilton Hall, Columbus, OH 43210.
Tel: 614-292-4831; Fax: 614-292-7659;Email: [email protected]
Search for more papers by this authorAbstract
Large craniofacial defects present a substantial clinical challenge that often requires the use of osteoconductive matrices and osteoinductive cues (i.e., bone morphogenetic proteins [BMP2]) to augment healing. While these methods have improved clinical outcomes, a better understanding of how the osteogenic fronts surrounding the defect, the underlying dura mater, and the cranial suture area contribute to healing may lead to more targeted therapies to enhance bone regeneration. We hypothesized that healing within a large bone defect will be precipitated from cells within the remaining or available suture mesenchyme abutting the edges of a murine critical sized defect. To investigate this hypothesis, 39 adult, wild-type mice were randomly arranged into groups (9 or 10 per group) by time (4 and 8 weeks) and treatment (control, acellular collagen sponge alone, or acellular collagen sponge loaded with a clinically relevant scaled dosage of BMP2). The skulls were then subjected to microcomputed tomography and histological analysis to assess bone regeneration in regions of interest within the defect area. A regional assessment of healing indicated that BMP2 drives greater healing than control and that healing emanates from the surgical margin, particularly from the margin associated with undisrupted suture mesenchyme. Though BMP2 treatment drove an increase in cell presence within the healing defect, there was no regional orientation of craniofacial stem cells or vascularity. Overall, these data reinforce that osteoconductive matrices in conjunction with osteoinductive peptides result in better healing of large calvarial defects. This healing is characterized as emanating from the surgical margin where there is an abundant supply of vasculature and progenitor cells.
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