Biomedical subjects

Samuel T Rhee

Publications and source records attributed to Samuel T Rhee.

6 recordsLinked to original sources

PubMed2006

Extracellular signal-related kinase and bone morphogenetic protein expression during distraction osteogenesis of the mandible: in vivo evidence of a mechanotransduction mechanism for differentiation and osteogenesis by mesenchymal precursor cells.

BACKGROUND: The goal in this study was to investigate the role of extracellular signal-related kinase (ERK) 1/2, a central regulator of mesenchymal stem cell differentiation, and its temporal relationship to bone morphogenetic protein (BMP) 2/4, a potent osteogenic growth factor, during live model distraction osteogenesis. METHODS: The authors examined histomorphometric expression through the early temporal sequence for both ERK 1/2 and BMP 2/4 during gradual distraction to 5.1 mm (n = 12 net). Comparison groups (group sizes, n = 12) included an acute critical-size defect of 5.1 mm and a subcritical-size defect of 2.1 mm. RESULTS: In the group gradually distracted to 5.1 mm, immunohistochemical analysis demonstrated significant intranuclear expression of ERK 1/2 within mesenchymal precursor cells at the osteotomy edges early in distraction (postoperative days 6 and 9). ERK 1/2 became increasingly localized to hypertrophic chondrocytes within the distraction regenerate during the later stages of distraction (postoperative day 16). Adjacent sections examined for BMP 2/4 expression established a close temporal and spatial correlation with ERK 1/2. BMP 2/4 expression was initially present in the regions surrounding mesenchymal precursor cells expressing ERK 1/2, but then developed most prominently within the cytoplasm of hypertrophic chondrocytes expressing ERK 1/2 late in distraction. Comparison groups consistently demonstrated either fibrous nonunion or bony union typical in fracture healing, depending on defect size. However, even specimens with subcritical-size defects and complete bony union were consistently found to have minimal ERK 1/2 expression. CONCLUSIONS: These data provide evidence that ERK 1/2 expression is present within mesenchymal precursor cells during distraction osteogenesis and that ERK expression correlates closely with BMP 2/4 expression. The presence of ERK 1/2 expression only during gradual distraction strongly implicates the concept that mechanical strain appears to be the key upregulating factor for ERK 1/2 expression, based on comparison with fracture-healing and critical-size defect specimens.

Animals↗

PubMed2005

Colocalization of c-Src (pp60src) and bone morphogenetic protein 2/4 expression during mandibular distraction osteogenesis: in vivo evidence of their role within an integrin-mediated mechanotransduction pathway.

Craniofacial distraction osteogenesis (DO) is an evolving reconstructive technique with expanding applications for the treatment of bony deficiencies of the facial skeleton. Mechanical force has been known to play a fundamental role in modulating sustained osteogenic response and therefore is believed to function as a critical regulator of DO. We hypothesize that key clustering components of an integrin-mediated signaling pathway, including c-Src (pp60), are necessary for mediating the response to mechanical force. The specific aim of this study is to demonstrate up-regulation of a key focal adhesion molecule, c-Src, selectively in new bone formation subject to the mechanical forces of distraction and to demonstrate a lack of that same up-regulation in new bone formation associated with simple fracture healing. An additional specific aim is to demonstrate colocalization of c-Src expression and bone morphogenetic protein (BMP 2/4) expression during mandibular DO. Using a rat model of mandibular DO, c-Src and BMP 2/4 expression were evaluated in critical size defects, subcritical size defects, and mandibles undergoing gradual distraction. Osseous regeneration was observed in the course of gradual distraction; this process was associated with increased expression of c-Src. Furthermore, the presence of BMP 2/4 closely approximated c-Src expression spatially and temporally, suggesting a link between cytoplasmic focal adhesion activation and the resultant nuclear regulation of osteogenic protein expression. In significant contradistinction, minimal c-Src expression was found in the subcritical-sized defects where the fractures healed secondarily but where no gradual distraction was performed. Instead, the new bone formation inherent in the secondarily healed subcritical-sized defects demonstrated expected BMP 2/4 expression but was devoid of an up-regulation of c-Src. Finally, as expected, minimal expression of both c-Src and BMP was found in fibrous nonunion specimens. C-src expression was observed during gradual distraction; furthermore, minimal c-Src expression was visualized during subacute and critical-size defect fracture healing. C-Src expression also closely approximated BMP expression during DO. These findings that c-Src expression is found primarily only during conditions of cyclic distraction forces strongly implicates that mechanical force during gradual distraction is associated with c-Src expression. These results provide in vivo support for previous in vitro evidence that mechanical force profoundly influences osseous regeneration during distraction osteogenesis by means of a c-Src dependent mechanotransduction pathway, resulting in increased expression of osteogenic proteins, including BMP 2/4.

Animals↗

PubMed2004

Conservative management of large avulsions of the lip and local landmarks.

Large lip avulsion injuries that involve significant tissue loss to the lip vermilion and other local landmarks can often pose a surgical dilemma for the reconstructive surgeon. Immediate reconstruction of these injuries are frequently performed using local flaps and adjacent tissue transfer to close the defect, but these repairs frequently suffer from the unfortunate consequence of increased associated scarring and further permanent distortion of the local anatomy. We present 2 patients sustaining dog bite injuries associated with extensive traumatic tissue loss to the lip vermilion and other local landmarks. These patients were treated conservatively with excellent functional and cosmetic results. A single minor surgical revision of 1 patient's cupid's bow was performed 1 year after injury. In cases of significant traumatic avulsion involving the lip vermilion and the perioral composite soft tissue, even with injuries including delicate anatomic landmarks, healing by secondary intention can be instituted as the initial treatment of choice in younger patients, often providing optimal results.

Administration, Topical↗

PubMed2003

Pediatric mandibular distraction osteogenesis: the present and the future.

Pediatric mandibular distraction osteogenesis (MDO) has become a mainstay of treatment for patients with micrognathia and retrognathia. As craniofacial surgeons have gained experience with MDO, the technique has become a safe and durable means of mandibular lengthening that avoids the significant morbidity of conventional surgical treatments. The full impact of this technique has not yet been realized for pediatric patients. Although studies have confirmed durable reconstruction of mandibular length with MDO, the range of applications of this technique is currently limited. As innovative clinicians continue to apply MDO to pediatric clinical craniofacial problems not easily treated with conventional means, the field of MDO will continue to mature. This article discusses current uses and examples of potential future applications of pediatric MDO. The development of novel and creative applications of MDO will advance the management of complex craniofacial anomalies, taking the field of craniofacial surgery into the future.

Child, Preschool↗

PubMed2002

Unique rodent model of distraction osteogenesis of the mandible.

Despite the increasing use of distraction osteogenesis (DO) of the mandible, the molecular mechanisms regulating new bone formation during DO remain poorly understood. The purposes of this study were (1) to establish a unique rodent model of DO capable of outlining parameters for new bone formation at the distraction site and (2) to determine a critical-size defect to differentiate osteogenesis resulting from distraction from conventional fracture healing at the osteotomy site. Adult Sprague-Dawley rats were fitted successfully with this newly developed distraction device. Analyses demonstrated that the device could distract the rat mandible reliably to 5.1 mm with complete union. Acute intersegmental gaps of 2 mm resulted in complete bony union in a manner consistent with fracture healing, whereas 3-mm acute gaps resulted in varying degrees of bony union. Acute intersegmental gaps of 5.1 mm invariably resulted in fibrous nonunion. In summary, the authors have developed a rodent model of DO of the mandible. Their distraction protocols resulted successfully in advancement to 5.1 mm with bony consolidation. Notable fracture healing occurred at immediate intersegmental spaces as large as 3 mm. A gap of 5.1 mm was sufficient to act as a critical-size defect, resulting consistently in fibrous nonunion. These findings validate the effectiveness of this distraction device and establish the critical-size defect of a rat mandible at more than 3 mm. This novel model of DO provides an effective method of examining fundamental mechanisms responsible for new bone formation in the craniofacial skeleton.

Animals↗

PubMed2002

Complete osseous regeneration of a large skull defect in a patient with cutis aplasia: a conservative approach.

Cutis aplasia (or aplasia cutis congenita) is a congenital absence of all skin layers, often extending through bone. This defect usually occurs in the scalp and can be extensive, exposing the dura mater, and deeper meninges. Treatment regimens for cutis aplasia have included early operative intervention, including skin and bone grafts, local scalp flaps, or free flaps to close the defect. In addition to the significant perioperative risks, these invasive procedures may inhibit the osteogenic potential of the dura to initiate and sustain bony closure of the defect. We report a case of an infant with Adams-Oliver syndrome and cutis aplasia involving a large portion of the skull that was treated conservatively with topical Silvadene dressings. No surgical treatment of bone or soft tissue reconstruction was necessary. This case report is the first to our knowledge to document complete bony restoration of the cranial vault through serial three-dimensional CT scans. The intensive therapeutic intervention in this case report allowed early discharge from the hospital, a gradual amelioration of the patient's alopecia as the hair-bearing scalp slowly covered the defect, and precluded the need for any subsequent bony reconstruction of the cranial vault. We hypothesize that conservative treatment of cutis aplasia maintains dural induction of osseous regeneration, and any treatment plan for bony defects of cutis aplasia should consider maintenance of dural integrity. Although further investigation is warranted, an initial trial of antimicrobial dressing care might optimally promote secondary closure of the cranial vault without the need for surgical intervention.

Administration, Cutaneous↗