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Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures, the cracks between the bones of the skull. When craniosynostosis occurs, it stops the skull from growing in certain directions, leading to secondary malformations of the brain. In order to allow the brain to grow normally, surgery is performed. Although surgical techniques are often able to improve the growth and development of children with craniosynostosis, more work needs to be done to expand our understanding of the biology that underlies craniofacial malformation and to further improve the treatment of these patients.
Our laboratory seeks to combine tissue engineering techniques with developmental biology to create tissues that can mimic normal suture function. By understanding the molecular mechanisms used by the body to exert control over bone formation, we aim to control the differentiation of tissues within the surgical site.
The pediatric craniofacial surgeon encounters many scenarios where osseous deficiencies must be corrected in the absence of a readily available supply of bone. Children between 2 and 10 years of age are especially problematic, as the dura has lost its osteoinductive potential to spontaneously heal calvarial defects by approximately 2 years of age; the gold standard option of split calvarial grafts are often unavailable due to the underdeveloped diploic space until approximately 10 years of age. Autologous bone grafts from distant sites such as the iliac crest or rib offer sources of bone, but such procedures are limited by low tissue yield and significant donor-site morbidity (such as infection, pain, hemorrhage, and nerve injury) in up to 8 percent of patients. Many studies have been conducted to evaluate various bone substitutes, such as cadaveric bone grafts, demineralized bone matrix, bioactive glass, hydroxyapatite, and methylmethacrylate. While some of these alternatives are promising, none is as reliable as autogenous bone, and all are fraught with disadvantages ranging from lack of bioactivity (and subsequent incompatibility with the growing pediatric craniofacial skeleton) to weakness and susceptibility to infection.
Recent advances in molecular biology have improved the understanding of craniofacial biology and made possible what some have termed “generative” craniofacial surgery. Instead of using exogenous materials, it is becoming increasingly realistic to repair craniofacial defects by inducing the generation of autogenous bone. Bone morphogenetic protein-2 (BMP2) therapy has been found to induce osteogenesis by chemical signaling. As with any powerful technology, a thorough evaluation of BMP2’s potential efficacy and associated morbidities must be conducted to allow for a properly informed risk / benefit analysis. Our laboratory is currently investigating the safety and efficacy of BMP2-based therapies for several different craniofacial applications.
Key Investigators: Joseph E. Losee, MD; Gregory M. Cooper, PhD
Current members of the Pediatric Craniofacial Biology Lab:
Gary E. DeCesare, MD
Project: BMP2 for craniofacial bone healing
Thomas Talamo, BS
Project: Rabbit dural cells and osteogenesis
Emily E. Lensie, BA
Research Specialist II
The Pediatric Craniofacial Biology Laboratory consists of 500 square feet of space in the Rangos Research Center. Included in the lab is one 4’ biological safety hood, 2 incubators, 1 refrigerator/freezer, 1 inverted and 1 upright microscope, balances, and standard glassware and supplies. We are equipped to study protein expression via Western Blotting and RNA expression via PCR. The Rangos Research Center contains several core facilities, including a sterilization facility, constant-temperature and cold-temperature rooms, DI water purification system, and a labware washing facility. Through collaboration with the Stem Cell Research Center, in the Rangos Research Center, we have access to a VivaCT40 (Scanco) microCT system and histological processing equipment. The laboratory is equipped with small equipment suitable for all proposed cell biology and protein/RNA chemistry experiments.
3550 Terrace Street
690 Scaife Hall
Pittsburgh, PA 15261