At the NYU Medical Center the Skirball Institute for Biomedical Research has been opened. Designed to pave the way for biomedical research in the next century, it holds the promise of laboratory developments with profound benefits for all clinical practice including plastic surgery. The current program includes long term clinical studies related to craniofacial distractions, computer graphic analysis of skeletal deformities, preoperative planning and the biology of craniofacial distraction and contraction of cranial suture biology.


Microvascular Research and Vascular Tissue Engineering Laboratory
Craniofacial Anomalies
Cleft Lip and Palate
Aesthetic Surgery
Psychological Aspects of Facial Deformity

Microvascular Research and Vascular Tissue Engineering Laboratory

1. Gene Therapy: Recent events have underscored the disparity between the promise and reality of gene therapy. The Microvascular Research and Vascular Tissue Engineering Laboratory has developed a novel delivery system for gene therapy utilizing the microcirculation of an explanted (ex vivo) microvascular free flap. This system circumvents many of the major difficulties hampering human gene therapy, including toxicity and targeting. The system may have significant utility for cancer gene therapy, as well as in the treatment of systemic diseases.

b. Microvascular Tissue Engineering: The promise of tissue engineering to produce "off-the-shelf" replacement organs has been thwarted by the difficulties in obtaining adequate microcirculation to sustain tissue viability. The laboratory has taken a two-tiered approach to solving this problem. They are conducting basic investigations into the roles of the wnt and hedgehog families of morphogens in tisse regeneraation such as occurs during wound healing. Hopefully, this will help clarify the fundamental mechanisms of vascular pattern formation, an area of critical importance for tissue engineering. A separate component is investigating the potential of ex-vivo microvascular beds to function as organizing scaffolds for tissue engineered constructs. This work holds the potential to make organ level tissue engineering possible in the near future.

c. Biomechanical regulation of Gene Expression: In collaboration with Dr. Jeffrey Holmes, MD, PhD, a biomechanical engineer at Columbia University studies have been initiated to investigate how biomechanical forces (stretch, pressure, etc.) turn gives on and off during the processes of wound healing. Clinically this is known to occur but the mechanisms remains unclear. Using micro-array (gene chip) technology, the laboratory will study the impact of strain upon the expression of over 60,000 genes. From this analysis it is hoped that the means to transform a bad scar into a good one, and a good scar into an invisible one will be attained.

d. Therapeutic Angiogenesis: Vascular growth factors (VEGF, FGF) have been utilized for coronary artery disease and ischemic peripheral vascular disease. Many chronic wounds also have an ischemic etiology and result in enormous healthcare costs socioeconomic and human toll. The laboratory is investigating the potential of gene therapy to induce increased vascularity (therapeautic angiogenesis) thereby improving. Novel mechanisms of improving wound healing (PEMF) are also being examined to develop improved therapeutics to accelerate the healing process.

e. Cellular Dysfuntion in Diabetic Wounds: Despite the enormous health care costs exacted by diabetic wounds, remarkably little is understood regarding their pathogenesis. We intend to dissect the cellular mechanisms and influences (i.e. hypoxia, hyperglycemic) occurring in diabetic wounds using a mouse model. From this information we hope to be able to develop more rational and effective therapeutics for chronic diabetic wounds.

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Craniofacial Anomalies

Court B. Cutting, M.D. in the Craniofacial Imaging Center

The Craniofacial Imaging Laboratory continues to make progress in the three dimensional visual reconstruction of the craniofacial skeleton and the development of ridge curves that allow quantitative measurements in any plane. This project has been supported by the Smile Train and by a National Institutes of Health (NIH) research grant. The Principal Investigator is Dr. Court B. Cutting in collaboration with Dr. Fred Bookstein at the University of Michigan. This research has developed computer graphics techniques to optimize the planning and execution of multiple piece mid-face skeletal advancements. Dr. Cutting has clinically adapted this research to robotic surgery in order to improve the results of skeletal segmental advancement by using intraoperative computer-assisted techniques.

Distraction osteognesis as a means of expanding or augmenting the craniofacial skeleton continues to be investigated by Dr. Joseph G. McCarthy and his colleagues. Previously, they had reported the use of an extraoral mandibular device in animals and humans. This research group continues to develop new distraction device technology with both intraoral and extraoral multiplanar devices. Distraction in multiple planes allows the surgeon to reconstruct the mandible with more accuracy. The large animal research continues to be performed in conjunction with technical and financial support from the Howmedica/Leibinger/Stryker Corporation. Less invasive methods of midface distraction are being explored experimentally by combining endoscopic surgery with distraction osteogenesis. This approach offers great promise for reducing the morbidity of the current midface advancement techniques. The effect of distraction osteogenesis on the muscles of mastication and the temporomandibular joint is being evaluated in both humans and in canine models. An animal model has been developed at the Center for Repair and Development to study the biology of mandibular distraction. Distraction osteogenesis in this model will be analyzed at both the gene and protein level using biomolecular reagents. Experiments are planned to combine gene therapy with distraction osteogenesis to maximize the rate and minimize the consolidation period of distraction. Animal models for cartilage distraction bone contraction are also being developed.

Tissue engineering is an exciting new area of research in the craniofacial laboratory. Prefabrication of cartilage and bone flaps with subsequent flap transfer to the cranium is being studied in an animal model. Analysis of these experiments will included histology and biomedical testing.

The biology of cranial suture fusion is being studied clinically using human specimens as well as experimentally in animal models. A large body of evidence has been gathered describing an important interaction between the brain, dura matter and cranial suture in craniosysnostosis. Analysis of physiologic and pathologic suture fusion at both the gene and protein level demonstrates that bone growth factors play a role in suture fusion. Numerous scientific publications have been published describing the biology of cranial suture fusion.

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Cleft Lip and Palate
Drs. Court B. Cutting, Barry Grayson and Lawrence Brecht continue to evaluate the role of presurgical molding devices for the dentoalveolus and nose. This important work allows a gingival closure to be performed at the time of the cleft lip repair. Early data indicate that the majority of children treated this way do not require a secondary bone graft to close their alveolar cleft. Studies are underway analyzing the cleft lip and nose shape in three dimensions postoperatively.

An animal model for a critical-sized defect of the maxillary alveolus has been developed. Once established, this model will be used to evaluate the efficacy of various bone promoting substances used in conjunction with a gingivoperiosteoplasty in closing alveolar clefts.

Dr. Grayson in conjunction with Dr. Cutting is developing a commercial software program for the 3-D cepalogram and has also been working with his colleagues in the Cleft Palate Team to develop a technique of preoperative nasal orthopedics in the cleft lip/palate patient.

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Aesthetic Surgery
Under the direction of Dr. Sherrell J. Aston a variety of clinical studies are in progress: the anatomy and efficacy of endoscopic brow lifts, the role of steroids in postoperative swelling following facialplasty, anatomic changes in the aging face, and comparisons between SMAS techniques and outcomes following facelifts.

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Psychological Aspects of Facial Deformity
Research into the psychology relating to facial deformity remains an important part of the Institute. Current research, under the direction of Drs. Alice Pope and Thomas Pruzinsky includes studies of family coping mechanisms associated with craniofacial deformities, facial expressions in children (and their mothers) with facial deformity (Dr. Harriet Oster), and the mode of parental coping with children undergoing distraction osteogenesis of the mandible.

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