Osseous tissue engineering with gene therapy for facial bone reconstruction.

OBJECTIVE: Facial osseous defects remain a major functional and esthetic challenge for the head and neck surgeon. Tissue engineering may provide advantageous alternatives to conventional therapies. The objective of the study was to evaluate the efficacy of gene therapy in the repair of osseous facial defects. STUDY DESIGN: Blinded, controlled, prospective animal experiment. METHODS: Thirty adult athymic nude rats were divided into five groups of six animals. Three groups were used as control subjects. Two groups were treated with 3.75 x 10(8) viral particles containing recombinant type 5 adenoviral vectors. One group received viruses that coded for beta-galactosidase production, another received viruses that coded for bone morphogenetic protein (BMP-2) production. After 120 days rats were examined at necropsy with precise planimetry, histological analysis of new bone growth, and radio-densitometric analysis of bone thickness. RESULTS: Radio-densitometric measurements showed that BMP-2-treated nude athymic rats had significantly enhanced osseous repair compared with control subjects when evaluated by both radio-densitometry and histological examination. CONCLUSION: Gene therapy-treated, immunosuppressed rodents had an enhanced osteoinductive repair of a dorsal osseous nasal defect.

Reliability of the melolabial flap for alar reconstruction.

OBJECTIVE: To review a series of alar reconstruction cases in which the melolabial flap was used. DESIGN: Case series. SETTING: University medical center and private practice. PATIENTS: One hundred five consecutive patients with alar defects, resulting from oncologic resection, in whom melolabial flap reconstruction was suitable. INTERVENTION: Single-stage melolabial flap reconstruction by a single surgeon (W.H.L.). MAIN OUTCOME MEASURE: Viability of the flap and presence or absence of surgical complications. RESULTS: There were no complete flap failures. Seven patients had partial necrosis of the distal end of the flap, and 3 of these instances occurred when the flap was rolled back onto itself to reconstruct the nasal vestibule; however, none of the patients required a subsequent operation or notching. Three patients developed hematoma, and 2 of them required a return to the operating room for control of bleeding. Four patients developed superficial infection, and 1 developed cellulitis of the cheek requiring opening of the wound and later revision of the flap. This was the only flap requiring revision. Fifteen patients required 3 or fewer corticosteroid infiltrations postoperatively for flap pin-cushioning or scar hypertrophy. CONCLUSION: The melolabial flap is a reliable tool in the reconstructive armamentarium of the facial plastic surgeon.

Repair of a rodent nasal critical-size osseous defect with osteoblast augmented collagen gel.

OBJECTIVES/HYPOTHESIS: Facial skeletal defects are a common challenge for the otolaryngologist. Type I collagen gels have shown promise in the repair of nonhealing critical size defects (CSDs) of facial bone by providing scaffolding for new bone growth by osteoblasts at the defect perimeter. The objective of the present study was to evaluate the effect that suspending osteoblasts within a type I collagen gel has on the repair of a rodent facial CSD. STUDY DESIGN: Randomized controlled trial using a rodent model. METHODS: A previously described facial CSD was created by removing the nasalis bones with a cutting burr to the level of the nasal mucosal membranes on 18 Sprague-Dawley rats. Groups of six animals were treated with an implant containing either 300 microg of type I collagen gel, 12 x 10(5) osteoblasts suspended within type I collagen gel, or 12 x 10(5) fibroblasts suspended within type I collagen gel for comparison. After 30 days the animals-were examined at necropsy with planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness. RESULTS: All animals had complete coverage with a thin layer of bone. Histological sectioning revealed an increased thickness in the osteoblast augmented group. Radiodensitometric measurements revealed a statistically significant increase in bone repair in the osteoblast group compared with the collagen-only group (P < or = .0005) and the fibroblast group (P < or = .04). CONCLUSION: Type I collagen gels augmented with an osteoblastic suspension significantly enhance the repair of nasal CSDs in a rodent model. The use of cultured bone precursor cells represents a leap forward in osteoengineering.

Repair of an osseous facial critical-size defect using augmented fibrin sealant.

OBJECTIVE: Osseous defects of the head and neck are a common challenge for the otolaryngologist. To develop improved reconstructive options, osteoconductive engineering experiments are being conducted. A nasal critical-size defect (CSD) model has previously been described in which less than 7% bone healing is observed over 6 months. An implant containing fibrin sealant with and without osteoprogenitor cells is evaluated in this model. STUDY DESIGN: Randomized controlled trial using a rodent model. METHODS: A nasal CSD was surgically created in 18 male retired breeder Sprague-Dawley rats. Six animals were not implanted with any material, six received fibrin sealant consisting of fibrin (25 mg/mL) and thrombin (1000 U/mL), and six were implanted with fibrin sealant and rat calvarial osteoprogenitor cells (1.8 x 10(6) cells/mL). Thirty days later, the animals were examined at necropsy by planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness. RESULTS: A thin layer of bone covered the defect in all of the treated animals. A statistically significant increase in bone density (P < .05) between fibrin sealant plus osteoprogenitor cells and each of the other groups was shown using radiodensitometric analysis. Histological analysis also confirmed this difference. CONCLUSION: Osteoprogenitor cells contained within fibrin sealant result in a greater augmentation of bone regeneration than controls or fibrin sealant alone.

Insulinlike growth factor 1- and 2-augmented collagen gel repair of facial osseous defects.

BACKGROUND: Defects of the facial bone structure are common problems for the facial plastic surgeon. Native type 1 collagen gels (T1CGs) have been shown to mediate repair of facial critical-size defects in rat models. OBJECTIVE: To evaluate the efficacy of T1CG augmented with insulinlike growth factor (IGF) 1, IGF-2, and a combination of IGF-1 and IGF-2 on the repair of facial critical-size defects in a rodent model. METHODS: Twenty-four retired male breeder Sprague-Dawley rats were divided into 4 groups of 6 animals. Facial critical-size defects were created by removing the nasalis bones with a bone-cutting drill. Defects were treated with 300 pg of type 1 collagen gel (T1CG), T1CG augmented with 3 microg of IGF-1, T1CG augmented with 3 microg of IGF-2, or T1CG augmented with a combination of 3 microg of IGF-1 and 3 microg of IGF-2. After 30 days the animals were examined at necropsy with precise planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness. RESULTS: Radiodensitometric measurements showed that IGF-2 augmentation resulted in greatest osseous healing, with measurements being statistically significant over those of all other groups (P< or = .03). Combination IGF-1 and IGF-2 had osseous healing that was intermediate between IGF-1 augmentation and IGF-2 augmentation alone, with measurements being statistically significant over those of unaugmented gels (P<.001) and IGF-1 augmentation (P< or = .03). Augmentation with IGF-1 resulted in healing that was significant over that of unaugmented gels (P< or = .04). CONCLUSION: Collagen gels augmented with IGF significantly enhance the osteoconductive repair of nasal critical-size defects in a rodent model, with IGF-2 showing highest efficacy.

Periosteal and galeal adhesiveness after a forehead lift in a rodent model.

PURPOSE: The aim of this study was to determine the strength of periosteal and galeal adhesiveness at particular intervals after subperiosteal and subperiosteal-subgaleal forehead lifting in a rodent model. MATERIALS AND METHODS: Sixty mice underwent a subperiosteal or subperiosteal-subgaleal coronal forehead lift procedure. Necropic and histologic examination of the periosteal, galeal, and bone interface was performed on postoperative days 2, 4, 6, 8, and 10, and the strength of the elevated flap reattachment to underlying tissues was measured. RESULTS: Tension analysis in the early postoperative period showed a higher avulsive force was required to re-elevate subgaleal-subperiosteal flaps than subperiosteal flaps. However, subperiosteal flap adhesiveness appeared to increase rapidly between postoperative days 4 and 8. By day 10, the force required to re-elevate subperiosteal flaps was significantly higher than that required for subgaleal-subperiosteal flaps (P < or = .0001). Histologic analysis showed an inflammatory response at the periosteum-bone interface, which maximized at postoperative day 6. CONCLUSIONS: In the early postoperative period, subgaleal-subperiosteal flaps had higher adhesiveness than subperiosteal flaps. However, by postoperative day 10, subperiosteal forehead flaps were substantially more adherent in this rodent model.

Repair of nasal defects using collagen gels containing insulin-like growth factor 1.

OBJECTIVE: Facial osseous defects are a common and challenging problem for the otolaryngologist-head and neck surgeon. Current methods of repair including synthetic grafts, cadaveric material, and autologous tissue have drawbacks of foreign body reactions, infectious agent transmission, and the morbidity of a second surgical site. In the effort to develop an ideal technique for osseous reconstruction, a critical-size facial defect has previously been developed in the Sprague-Dawley rat. This model exhibits less than 10% healing by surface area over 6 months. A novel approach to osseous reconstruction is attempted using this model with type I collagen gel augmented with insulin-like growth factor 1 (IGF-1). STUDY DESIGN: Randomized controlled trial using a rodent model. METHODS: Twelve adult male Sprague-Dawley rats underwent a surgical procedure to produce a critical-size nasal defect by removing the nasal bones with a cutting burr. Six animals were repaired with 300 microg of type I collagen gel. Six animals were repaired with 300 microg of type I collagen gel augmented with 3.0 microg of IGF-1. Thirty days later, the animals were examined after necropsy. Precise planimetry, radiodensitometric analysis, and histologic sectioning were performed. RESULTS: All animals had complete coverage of this defect with a thin layer of bone. Radiodensitometric analysis indicated that there was a statistically significant (P < .037) increase in bone density in the collagen plus IGF-1 group compared with that of collagen only. In addition, histologic evaluation revealed increased bone density and thickness in the IGF-1 group. CONCLUSION: Type I collagen gel augmented with IGF-1 results in a significant increase in healing of a nasal critical-size defect in a rodent model.

A nasal critical-size defect: an experimental model for the evaluation of facial osseous repair techniques.

OBJECTIVE: To create a standardized nonhealing defect of craniofacial, minimal load-bearing, endochondral type bone with geometric properties that are amenable to quantitative and biomechanical testing that can be used to develop new osteoconductive and osteoinductive engineering repair techniques. DESIGN: Before-and-after randomized trial of an anatomical description. SUBJECTS: Twenty-four retired male breeder Sprague-Dawley rats. METHODS: A standardized osseous defect was created by removing the nasal bones with a cutting burr to the level of the nasal mucosal membranes. The defects were not repaired, and groups of 8 animals were examined using planimetry, computed tomographic scanning, and histological analysis at 1, 3, and 6 months following surgery to quantify defect repair. RESULTS: Mean repair rate by surface area measurements at 1, 3, and 6 months was 5.75%, 4.89%, and 7.09%, respectively. Results from histological analysis revealed that the defects were filled with fibrous tissue. Computed tomographic scans showed the bone defect without repair. CONCLUSION: This nasal osseous defect fulfills criteria to be considered as a critical-size defect that can be used to investigate new techniques for bone reconstruction.

Facial keloids. A 15-year experience.

BACKGROUND: Keloids are relatively common sequelae of trauma to the skin of the head and neck. A wide variety of treatment approaches developed over the years document the difficulty in eradicating these lesions. OBJECTIVE: To review the senior author's (W.H.L) 15-year experience in treating keloids both medically and surgically. DESIGN: A retrospective analysis of 202 patients with histologically documented keloids of the head and neck with at least a 2-year follow-up. RESULTS: A combination of precise surgical excision, postoperative steroid infiltration, silicone sheeting, and conservative auricular radiotherapy has resulted in an acceptable 15% recurrence rate overall. CONCLUSIONS: The treatment of facial keloids remains a challenge for the facial plastic and reconstructive surgeon. Precise surgical techniques with adjuvant therapies have resulted in a relatively low recurrence rate.

Follow-up of University of Virginia experience with the modified Lothrop procedure.

Current surgical treatment of the frontal sinus disease include external approaches to obliterate or ablate the sinus and both external and transnasal methods to restore drainage into the nasal cavity. The original Lothrop procedure resects the medial frontal sinus floor, superior nasal septum, and intersinus septum, creating a large frontonasal communication. However, as described, the external approach used in this procedure often allowed medial collapse of soft tissue and the stenosis of the nasofrontal communication. This report further relates our experience with the modified transnasal endoscopic Lothrop procedure using suction drills for cases in which frontal recess exploration had failed to relieve obstruction of the frontal sinus. We present an update of the University of Virginia experience in performing the modified Lothrop procedure in 20 patients from 10/93 to 4/95. Our findings over the follow-up period (average 12 months) have verified that this procedure is effective, with a 95% patency rate for the surgically enlarged frontal sinus ostium. When compared to osteoplastic flap with fat obliteration, the modified transnasal Lothrop procedure offers the advantages of a less invasive procedure with a shorter and usually no hospitalization, less morbidity, and the increased ability to evaluate post-operatively for recurrent disease. A patient charge analysis was also performed comparing patients undergoing frontal sinus obliteration during the same time period, revealing an additional benefit of decreased patient costs for the modified transnasal Lothrop procedure. None of our patients experienced complications, and all showed significant improvement, if not complete resolution of their symptoms. Although this procedure has produced favorable results, it should be noted that this procedure is technically demanding and will require further long term follow-up to verify its efficacy and proper role in the spectrum of surgical approaches for the treatment of chronic sinusitis.

Correction of velopharyngeal insufficiency with furlow palatoplasty.

OBJECTIVE: To evaluate the authors' experience with Furlow palatoplasty for velopharyngeal insufficiency. DESIGN: Review of 8 cases over a 3-year period. SETTING: Regional private practice hospital affiliated with a teaching university. PATIENTS: Eight patients aged 4 to 14 years with symptoms and signs of velopharyngeal insufficiency underwent Furlow palatoplasty. Four patients had submucous or soft palate clefts without previous intervention. Four patients had undergone previous surgery for cleft palate. INTERVENTION: All patients underwent Furlow palatoplasty. MAIN OUTCOME MEASURES: Fiberoptic nasopharyngeal examination and speech analysis. RESULTS: Seven of 8 patients exhibited good palate closure and marked improvement in speech. One patient exhibited good closure but had mild nasal emission and hypernasality, which responded to speech therapy after surgery. CONCLUSION: Furlow palatoplasty is a useful technique for the correction of velopharyngeal insufficiency in selected patients.

Nasal reconstruction using an osteoconductive collagen gel matrix.

BACKGROUND: Congenital malformations, granulomatous diseases, and trauma can all cause destruction of the nasal structural framework, resulting in functional nasal obstruction and altered facial cosmesis. Current methods of nasal reconstruction include cartilaginous and bony grafts, Silastic implants, and homograft only materials. However, these techniques have significant functional and cosmetic drawbacks and are not risk free. Native, isotonic, neutral-pH, space-filling type I collagen gels have been shown to mediate total repair of critical-size collagen grafts provide a framework for rapid intramembranous ossification and osteoconduction of bone from the perimeter of a defect, resulting in total bony coverage. OBJECTIVE: To evaluate a novel approach to nasal reconstruction using a major defect of the bony nasal dorsum with a type I collagen gel matrix. DESIGN: Sixteen retired male breeder Sprague-Dawley rats were divided into control and experimental groups. The nasal bones were exposed through a dorsal incision and completely removed with a bone-cutting drill to the level of the mucosal membranes of the nasal vestibule. Defects in the experimental animals were then implanted with 200 micrograms of type I collagen gel, with control animals receiving no inlay. After 6 weeks, the animals were examined with three-dimensional computed tomography before necropsy, at which time the defects were photographed, measured by planimetry, and sectioned for histologic analysis. RESULTS: Experimental defects were observed to manifest 100% surface area healing with a thin layer of bone using a type I collagen gel osteoconductive implant for nasal reconstruction. Conversely, control animals showed only a 5.7% (+/- 3.7% SD) healing by area. Histologic sections of the collagen gel implant revealed restoration of the anatomy with a thin plate of immature bone spanning the defect in continuity with the cartilage of the nasal septum and with apparent preservation of maxillonasalis suture lines. CONCLUSIONS: Native, isotonic, neutral-pH, space-filling collagen gels positively influenced the repair of large nasal defects, which showed minimal bone closure in untreated animals. Their use in this role merits further investigation.

Modified transnasal endoscopic Lothrop procedure: further considerations.

The Lothrop procedure resects the medial frontal sinus floor, superior nasal septum, and intersinus septum to create a large frontonasal communication. However, the external approach often allowed medial collapse of soft tissue and stenosis of the nasofrontal communication. We describe a modified transnasal endoscopic Lothrop procedure in which drills are used for cases in which frontal recess exploration fails to relieve obstruction of the frontal sinus. The lateral bony walls are preserved, and medial collapse does not occur. The mucosa of the posterior table and posterior nasofrontal duct is preserved, and a single common frontal opening is created. We have found this approach to be safe and reliable. Fourteen patients have undergone this procedure without complication, achieving resolution or improvement of their symptoms and maintaining wide patency of the frontonasal opening. We recognize that long-term follow-up will be required but remain encouraged with our favorable results to date.

The soft-tissue shaving procedure for removal of adipose tissue. A new, less traumatic approach than liposuction.

OBJECTIVE: To introduce the soft-tissue shaving cannula, a new, precise alternative to conventional liposuction that embodies an entirely different method of soft-tissue extraction and that appears to be less traumatic and more precise than methods currently used in liposuction. DESIGN: Nonrandomized, nonblinded comparison of the soft-tissue shaver and conventional liposuction devices in fresh cadavers, followed by clinical use of the liposhaver in selected patients undergoing cosmetic facial liposuction. INTERVENTIONS: Conventional liposuction devices and the soft-tissue shaving cannulas in fresh cadavers (< 8 hours old). A submental lipectomy and a melolabial fold liposhaving were performed in a clinical setting. OUTCOME MEASURES: Subjective evaluation by the operating surgeons. RESULTS: The fat was cleanly shaved and the contour result was even, without dimpling or asymmetry. CONCLUSIONS: Our early experiences suggest that this new liposhaving technique may offer a precise, less traumatic alternative to conventional liposuction. Fat can be shaved in an open fashion under direct vision. It does not rely on a vacuum seal. The soft-tissue shaving cannula shaves fat one layer at a time. The depth of each layer removed, the depth of soft-tissue injury, and the optimal settings and sizes for various procedures remain to be reported.

Comparison of topical fibrin glue, fibrinogen, and thrombin in preventing seroma formation in a rat model.

Fibrin glue has been shown to decrease seroma formation in animal models. To further delineate this mechanism, the efficacy of fibrin glue was compared to topical fibrinogen and thrombin in preventing postoperative seromas. A model consistently producing seromas was developed by bilateral neck dissection, lymphadenectomy, and submandibular sialoadenectomy in the Sprague-Dawley rat. Groups of 20 rats underwent this procedure and were blindly treated with either fibrin glue, fibrinogen, thrombin, or saline control. Necropsy on postoperative day 5 revealed a statistically significant (chi-squared) decrease in seroma incidence using fibrin glue (0%) and fibrinogen (15%), while thrombin (95%) and saline (100%) were ineffective in preventing seromas. The use of fibrin glue and fibrinogen in this role merits further investigation.

Seroma prevention using fibrin glue in a rat mastectomy model.

Seromas are a frequent complication of mastectomy (17% to 53%) in humans and are correlated to skin flap elevation, lymphovascular interruption, and drainage into surgically created potential spaces. The use of intraoperative topical fibrin glue to reduce morbidity in rats undergoing radical mastectomies has been evaluated. A model consistently producing seromas was developed by radical mastectomy and lymphadenectomy in the Sprague-Dawley rat. A fibrin glue application procedure was tested using this model. The double-blinded protocol called for spray application of saline or fibrin glue to mastectomy wounds followed by sequential inspection and necropsy on postoperative days 5, 8, 11, and 14. Topical fibrin glue was shown to be statistically significant in decreasing the presentation of seromas following a radical mastectomy in the Sprague-Dawley rat.

Seroma prevention using fibrin glue during modified radical neck dissection in a rat model.

Seroma is a frequent sequelae of neck dissection involving cervical lymphadenectomy. The incidence is correlated with flap elevation, lymphovascular interruption, and tissue removal. Current methods of resolving seroma, such as vacuum drainage, are not risk free. A novel approach to this problem was the use of intraoperative topical fibrin glue. A model producing seromas was developed by modified radical neck dissection on Sprague-Dawley rats. Forty rats underwent this procedure. Twenty rats were treated with saline solution (control group) and 20 were treated with fibrin glue. At necropsy on day 5, a significant reduction in the frequency of seroma was noted in the fibrin glue group. Seventeen of 20 control rats had seroma whereas only 2 of 20 experimental animals had serous collection. The Fisher exact statistical correlation revealed p less than 0.000002; therefore, the use of fibrin glue in this role merits further evaluation.