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Transforming the degradation rate of beta-tricalcium phosphate bone replacement using 3D printers [Meeting Abstract]
Shen, C; Wang, M; Witek, L; Cronstein, B; Torroni, A; Flores, R; Coelho, P
Background/Purpose: b-Tricalcium phosphate (b-TCP), the most common synthetic bone replacement product, is frequently used in craniofacial reconstruction. Although solid b-TCP can be absorbed over time, the slow degradation rate (1%-3%/year) predisposes this product to exposure, infection, and fracture, limiting its use in the growing face where implants are required to grow and remodel with the patient. Our tissue engineering laboratory has successfully leveraged 3D printers to manufacture 3D-printed bioactive ceramic (3DPBC) scaffolds composed of b-TCP in an architecture which optimizes the needs of rigidity with efficient vascular ingrowth, osteogenesis, and degradation kinetics. The latter qualities are further optimized when the osteogenic agent dipyridamole (DIPY) is used. This long-term animal study reports on the new degradation kinetics profile achievable through this novel manufacturing and tissue engineering protocol. Methods/Description: Twenty-two 1-month-old (immature) New Zealand white rabbits underwent creation of unilateral 10 mm calvarial defects with ipsilateral 3.5 +/- 3.5 mm alveolar defects. Each defect was repaired with b-TCP 3DPBC scaffolds coated with 1000 mM DIPY. Rabbits were killed at 8 weeks (n = 6), 6 months (n = 8), and 18 months (n = 8). Bone regeneration and scaffold degradation were calculated using micro-CT images and analyzed in Amira software. Cranial and maxillary suture patency and bone growth were qualitatively analyzed using histologic analysis.
Result(s): Results are reported as a percentage of volumetric space occupied by either scaffold or bone. When comparing time points 8 weeks, 6 months, and 18 months, scaffolds showed significant decreased defect occupancy in calvaria (23.6% +/- 3.6%, 15.2% +/- 1.7%, 5.1% +/- 3.4%; P < .001) and in alveoli (21.5% +/- 3.9%, 6.7% +/- 2.7%, 0.1% +/- 0.2%; P < .001), with annual degradation rates 55.9% and 94.2%, respectively. Between 8 weeks and 18 months, significantly more bone regenerated in calvarial defects (25.8% +/- 6.3% vs 55.7% +/- 10.3%, P < .001) and no difference was found in alveolar defects (28.4% +/- 6.8% vs 32.4% +/- 8.0%, P = .33). Histology showed vascularized, organized bone without suture fusion.
Conclusion(s): The degradation kinetics of b-TCP can be altered through 3D printing and addition of an osteogenic agent. Our study demonstrates an acceleration of b-TCP degradation from 1% to 3% a year to 55% to 95% a year. Absorbed b-TCP is replaced by vascularized bone and there is no damage noted to the growing suture. This additive manufacturing and tissue engineering protocol has implication to future reconstruction of the craniofacial skeleton
EMBASE:631558383
ISSN: 1545-1569
CID: 4414672
Comparative study of skeletal stability following mild, moderate, and severe lefort i advancement in patients with cleft lip and palate [Meeting Abstract]
Wangsrimongkol, B; Flores, R; Staffenberg, D; Rodriguez, E; Shetye, P
Background/Purpose: Le Fort I advancement surgery is challenging in patients with clefts because of the palatal scar tissues. In this study, we investigated the outcome of Le Fort I advancement surgery (mild, moderate, and severe groups) and 1-year skeletal stability in patients with cleft lip and palate. Methods/Description: A retrospective chart review was performed to identify patients with nonsyndromic unilateral or bilateral cleft lip and palate who underwent maxillary Le Fort I advancement at skeletal maturity from 2013 to 2019. To satisfy the inclusion criteria, all patients had to have diagnostic quality cone beam computed tomography (CBCT) prior to surgery (T0), immediately postoperative (T1), and at 1-year follow-up (T2). A total of 59 patients (unilateral n = 34, bilateral n = 25) who underwent Le Fort I advancement was identified. Nineteen of these 59 patients were excluded due to insufficient radiographic records; thus, 40 patients with complete records were included in the study. The sample was comprised of 9 females and 31 males, with an average age of 19.1 +/- 3.21 years at the time of the surgery. Lateral cephalograms were extracted, traced, and superimposed using Dolphin Imaging software (V 11.95). Horizontal surgical movement (T0-T1) and postoperative relapse (T1-T2) at skeletal and dental level were quantified as linear changes at point A and upper incisor edge (U1-tip), respectively. Patients were divided into 3 groups according to the severity of surgical movement: mild (<5 mm, n = 9), moderate (5-10 mm, n = 20), and severe (>10 mm, n = 11). The statistical analysis was performed using 2-way repeated-measures ANOVA to test the difference of surgical movements and postoperative relapse between groups.
Result(s): The mean advancement (T0-T1) of all patients at point A was 8.1+/-2.8 mm and at U1-tip was 7.7+/-2.6 mm. In the mild, moderate, and severe groups, the mean advancement at point A were 4.6 +/- 1.3 mm, 7.7+/-1.1 mm, and 11.6+/-1.2 mm, and at U1-tip were 5.7+/-2.9 mm, 7.4 +/- 1.3 mm, and 10 +/- 2.6 mm, respectively. There were significant skeletal and dental advancements in all the 3 groups following Le Fort I surgery (P < .0001). At 1-year follow-up, the mean relapse (T1-T2) at point A was 1.2 +/- 1.1 mm and at U1-tip was 0.07 +/- 1.9 mm. When analyzed within the mild, moderate, and severe groups, the mean relapse at point A were 0.8 +/- 0.7 mm, 1.2 +/- 0.9 mm, and 1.9+/-1.5 mm and at U1-tip were -0.4+/-1.6 mm, 0.4+/-2.1 mm, and -0.2 +/- 1.5 mm, respectively. There was no significant difference in the relapse amount between the mild, moderate, and severe groups at skeletal and dental components (P > .05).
Conclusion(s): Le Fort I advancement surgery successfully corrected maxillary hypoplasia in patients with cleft lip and palate in all the 3 groups. This study also demonstrated that larger advancement in the severe group can result in equivalent skeletal stability when compared to the mild and moderate advancement. Though mild skeletal relapse was observed in all the 3 groups, none of the patients had to be reoperated
EMBASE:631558289
ISSN: 1545-1569
CID: 4417642
A 70-year history of unilateral cleft lip repair: A simulator-based symposium [Meeting Abstract]
Cutting, C; Flores, R; Wang, Q; Tao, Y; Sifakis, E
Background/Purpose: The evolution of primary unilateral cleft lip repair represents a series of incremental modifications pioneered by a distinct group of master surgeons. It is through understanding the purpose of each evolutionary step, the limits and compromises of these steps, and the subsequent modifications which followed, can a greater understanding of the art of cleft lip repair be realized. This course will trace the conceptual development of unilateral cleft lip repair over the past 70 years using a novel, real-time computer-based cleft lip simulator. A first order accurate biophysics implementation within the simulator will be used to demonstrate the cleft lip repair techniques described to reveal the strengths and weaknesses of each stage of unilateral lip repair development. The course will begin with the Tennison Randall lower triangular lip repair, as it is still in common use today. This will be followed by Skoog, Wynn, and Mustarde adding an upper triangle to the lip repair. The various stages in the progression of the Millard repair will then be carefully traced along with the biophysics which are likely responsible for why Millard altered his original design. The modifications of the Millard design by other surgeons, and the reasons for them, will then be carefully traced. The modifications covered will be those of Noordhoff, Mohler, Cutting, Fisher, and others. The interaction between lip repair technique and primary correction of the cleft-lip nasal deformity will be discussed in detail. Simulator-based demonstrations will be augmented with patient examples from the senior author's clinical practice which illustrate the conceptual difficulties encountered at various stages in the historical development of primary unilateral cleft lip and nose repair. Methods/Description: The principal method used in this course will be real-time computer-based surgical simulation. A unilateral cleft lipnose model involving skin, mucosa, muscle, bone, cartilage, and teeth was derived from an MR scan of an adolescent with an unrepaired unilateral cleft. Alterations in the model are illustrated with first-order accurate biophysics using a new software base called projective dynamics. Surgical tools provided are scalpel, suture, hook, and undermine of both skin/mucosa and bone/cartilage. Surgical "'history" files are used to step through a succession of cleft lip repairs in the surgical eclectic. The presentation will be augmented with photographs from the senior author's long career further illustrating why successive alterations in technique were made
EMBASE:631558098
ISSN: 1545-1569
CID: 4417712
Clinical course of temporomandibular joint ankylosis in pediatric patients with craniofacial anomalies [Meeting Abstract]
Ramly, E; Yu, J; Eisemann, B; Yue, O; Alfonso, A; Kantar, R; Staffenberg, D; Shetye, P; Flores, R
Background/Purpose: Temporomandibular joint (TMJ) ankylosis is an uncommon but debilitating condition which can affect feeding, speech, dental health, facial growth, and quality of life. We present an institutional experience treating congenital and acquired TMJ ankylosis, detailing outcomes and potential risk factors of recurrence. Methods/Description: Patients with ankylosis of the TMJ were identified through retrospective chart review (1976-2019). Clinical records, operative reports, and imaging studies were reviewed for demographics, surgical operations, and ankylosis including mean interincisal opening (MIO) and reankylosis.
Result(s): Forty-four TMJs with bony ankylosis were identified in 28 patients, 27(96.4%) of whom had syndromes. Mean age at any initial mandibular surgery was 3.7+/-3.6 (range: 0-14 years). Follow-up was 13.7 +/- 5.9 years. Sixteen (57.1%) patients had bilateral ankylosis. Nine cases of ankylosis were congenital, 16 were iatrogenic (4.5 +/- 3.7 years from initial distraction osteogenesis or autologous mandibular reconstruction) referred from outside institutions in 6 cases, and 3 were postinfectious. Patients having their first mandibular operation at a younger age had more frequent reoperations for recurrent TMJ ankylosis, although this did not reach statistical significance. Improvement in MIO was 21.4 +/- 7.3 mm. Ankylosis recurred in 21(75%) cases, 11 of which were iatrogenic, requiring an average of 2 reoperations (range: 1-8). Five patients with congenital TMJ ankylosis required gastrostomy and remained at least partially dependent. Five patients had tracheostomy at the time of TMJ ankylosis surgery: 2 were eventually decannulated and 3 required repeat tracheostomy after ankylosis recurrence and remained tracheostomy-dependent.
Conclusion(s): Craniofacial anomalies, younger age at mandibular surgery, and number of operations portend to increased risk of TMJ ankylosis as well as tracheostomy and gastrostomy dependence. Despite initial improvement in postoperative MIO, pediatric TMJ ankylosis is associated with high recurrence and multiple reoperations
EMBASE:631558218
ISSN: 1545-1569
CID: 4417672
The nasoalveolar molding cleft protocol: Long-term results from birth to facial maturity [Meeting Abstract]
Yarholar, L; Shen, C; Grayson, B; Cutting, C; Staffenberg, D; Shetye, P; Flores, R
Background/Purpose: We present the first long-term outcomes analysis of the nasoalveolar molding (NAM) treatment protocol on patients with a cleft followed from birth to facial maturity. Methods/Description: Single-institution retrospective review of all patients with a cleft who underwent NAM between the years 1990 and 2000. All study patients completed cleft care treatment at the same institution and were followed by the same team members. Our institution's treatment protocol offers NAM to patients with a significant cleft nasal deformity and/or widely displaced alveolar segments. All patients underwent primary cleft lip and nasal repair prior to the age of 6 months. Gingivoperiosteoplasty (GPP) is performed, when possible, at the time of lip repair. Cleft palate repair is performed by 1 year of age. Collected data include surgical and orthodontic outcomes of cleft care such as cleft lip and palate repair, GPP, alveolar bone grafting (ABG), speech surgery for velopharyngeal insufficiency (VPI), palatal fistula repairs, orthognathic surgery, and revision surgery to the nose and/or lip.
Result(s): A total of 135 patients met the inclusion criteria. Mean length of follow-up was 18.8 years. Eighty-nine patients presented with a unilateral cleft (UNI) and 46 with a bilateral cleft (BI); 84% (113/135) of patients underwent GPP (UNI: 78% [69/89]; BI: 96% [44/46]), 43% (58/135) of patients underwent ABG (UNI: 40% [36/89]; BI: 48% [22/46]), 18% (24/135) of patients underwent speech surgery for VPI (UNI: 14% [12/89]; BI: 26% [12/46]), 3% (4/135) of patients underwent palatal fistula repair (UNI: 0% [0/89]; BI: 9% [4/46]), 31% (42/135) underwent orthognathic surgery (UNI: 22% [20/89]; BI: 48% [22/46]), and 11% (15/135) underwent revision surgery to lip, nose, or both prior to facial maturity (UNI: 9% [8/89]; BI: 15% [7/46]]. Of the patients who underwent GPP, 61% (69/113) did not require ABG (UNI: 65% [45/69]; BI: 55% [24/44]) and 42% (48/113) required neither ABG nor orthognathic surgery (UNI: 51% [35/69]; BI: 30% [13/44]).
Conclusion(s): Clinical outcomes of the NAM treatment protocol from birth to facial maturity demonstrate a low rate of revision surgery to the lip and nose, as well as a low fistula and VPI rate. The frequency of orthognathic surgery reported in this study is consistent with published data. In addition, 42% of patients who underwent NAM with GPP required neither ABG nor orthognathic surgery
EMBASE:631558226
ISSN: 1545-1569
CID: 4417662
Bone Tissue Engineering in the Growing Calvaria Using Dipyridamole-Coated, Three-Dimensionally-Printed Bioceramic Scaffolds: Construct Optimization and Effects on Cranial Suture Patency
Maliha, Samantha G; Lopez, Christopher D; Coelho, Paulo G; Witek, Lukasz; Cox, Madison; Meskin, Alan; Rusi, Sejndi; Torroni, Andrea; Cronstein, Bruce N; Flores, Roberto L
BACKGROUND:Three-dimensionally-printed bioceramic scaffolds composed of β-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally-printed bioceramic/dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated. METHODS:Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally-printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 μm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 μM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro-computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning. RESULTS:Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 μm, coated in 1000 μM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro-computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations. CONCLUSION/CONCLUSIONS:The authors present an effective pediatric bone tissue-engineering scaffold design and dipyridamole concentration that is effective in augmentation of calvarial bone generation while preserving cranial suture patency.
PMID: 31985634
ISSN: 1529-4242
CID: 4293882
Zygomatic Rotation-Advancement: A New Concept for the Correction of Exorbitism in Patients With Syndromic Craniosynostosis
Diaz-Siso, J Rodrigo; Gibson, Travis L; Plana, Natalie M; Yue, Olivia Y; Flores, Roberto L
BACKGROUND:The exophthalmos and class III malocclusion seen in Crouzon syndrome can be treated by Le Fort III advancement/distraction. However, reconstructive options for zygomatic retrusion are limited. The authors describe the repair of isolated exorbitism in a patient with Crouzon syndrome, via bilateral zygomatic rotation-advancement. METHODS:A 34-year-old woman with Crouzon syndrome complained of exorbitism and malar hypoplasia. Four years prior, she declined Le Fort III advancement and underwent orthodontic/orthognathic correction of malocclusion. Radiographs were used to develop a computerized surgical plan. Bilateral periorbital osteotomy with advancement/rotation of the zygomatic process was performed using custom osteotomy guides and plates. Images obtained immediately postoperative and 3- and 19-month postoperative were compared to assess surgical stability, accuracy, and soft tissue changes. RESULTS:Decreased globe exposure and increased malar prominence have improved facial balance. Superimposed pre- and postoperative radiographs demonstrate bilateral advancement of the zygomatic body and inferior orbital rim. Superimposition of immediate postoperative and 19-month radiographs showed no relapse. Soft tissue histogram showed increased prominence of the malar eminence, lateral orbital rim, and cheek. CONCLUSIONS:Zygomatic rotation-advancement proved a safe, effective, stable, and predictable treatment for isolated malar hypoplasia in a patient with Crouzon syndrome. Virtual planning can enhance novel complex craniofacial procedures.
PMID: 31246629
ISSN: 1536-3732
CID: 3963842
Knowledge and Skills Acquisition by Plastic Surgery Residents Through Digital Simulation Training: A Prospective Randomized Blinded Trial
Kantar, Rami S; Alfonso, Allyson R; Ramly, Elie P; Cohen, Oriana; Rifkin, William J; Maliha, Samantha G; Diaz-Siso, J Rodrigo; Eisemann, Bradley S; Saadeh, Pierre B; Flores, Roberto L
INTRODUCTION/BACKGROUND:Simulation is a standard component of residency training in many surgical subspecialties, yet its impact on knowledge and skills acquisition in plastic surgery training remains poorly defined. We evaluated the potential benefits of simulation-based cleft surgery learning in plastic surgery resident education through a prospective, randomized, blinded trial. METHODS:Thirteen plastic surgery residents were randomized to a digital simulator or textbook demonstrating unilateral cleft lip (UCL) repair. The following parameters were evaluated before (pre-intervention) and after (post-intervention) randomization: knowledge of surgical steps, procedural confidence, markings performance on a three-dimensional (3D) stone model, and surgical performance using a hands-on/high-fidelity 3D haptic model. Participant satisfaction with either educational tool was also assessed. Two expert reviewers blindly graded markings and surgical performance. Intra-class correlation coefficients (ICC) were calculated. Wilcoxon signed-rank and Mann-Whitney U tests were used. RESULTS:Interrater reliability was strong for pre-intervention and post-intervention grading of markings (ICC=0.97; p<0.001 and ICC=0.96; p<0.001) and surgical (ICC=0.83; p=0.002 and ICC=0.81; p=0.004) performance. Post-intervention surgical knowledge (40.3±4.4 vs. 33.5±3.7; p=0.03), procedural confidence (24.0±7.0 vs. 14.7±2.3; p=0.03), markings performance (8.0±2.5 vs. 2.9±3.1; p=0.03), and surgical performance (12.3±2.5 vs. 8.2±2.3; p=0.04) significantly improved in the digital simulation group compared to pre-intervention, but not in the textbook group. All participants were more satisfied with the digital simulator as an educational tool (27.7±2.5 vs. 14.4±4.4; p<0.001). CONCLUSIONS:We present evidence suggesting that digital cognitive simulators lead to significant improvement in surgical knowledge, procedural confidence, markings performance, as well as surgical performance.
PMID: 31609286
ISSN: 1529-4242
CID: 4140222
Dipyridamole-loaded 3D-printed bioceramic scaffolds stimulate pediatric bone regeneration in vivo without disruption of craniofacial growth through facial maturity
Wang, Maxime M; Flores, Roberto L; Witek, Lukasz; Torroni, Andrea; Ibrahim, Amel; Wang, Zhong; Liss, Hannah A; Cronstein, Bruce N; Lopez, Christopher D; Maliha, Samantha G; Coelho, Paulo G
This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (β -TCP) in an immature rabbit model through the time of facial maturity. The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. Additionally, long-term degradation of scaffold constructs was evaluated. At 24 weeks in vivo, DIPY-3DPBC scaffolds demonstrated volumetrically significant osteogenic regeneration of calvarial and alveolar defects comparable to autogenous bone graft with favorable biodegradation of the bioactive ceramic component in vivo. Characterization of regenerated bone reveals osteogenesis of organized, vascularized bone with histologic and mechanical characteristics comparable to native bone. Radiographic and histologic analyses were consistent with patent craniofacial sutures. Lastly, through application of 3D morphometric facial surface analysis, our results support that DIPY-3DPBC scaffolds do not cause premature closure of sutures and preserve normal craniofacial growth. Based on this novel evaluation model, this DIPY-3DPBC scaffold strategy is a promising candidate as a safe, efficacious pediatric bone tissue engineering strategy.
PMID: 31804544
ISSN: 2045-2322
CID: 4218802
Effect on Facial Growth of the Management of Cleft Lip and Palate
Farber, Scott J; Maliha, Samantha G; Gonchar, Marina N; Kantar, Rami S; Shetye, Pradip R; Flores, Roberto L
Treatment of cleft lip and palate ordinarily requires multiple interventions spanning the time of birth to adulthood. Restriction of facial growth, a common occurrence in affected children, is due to multiple factors. There are multiple surgical and therapeutic options, which may have influence on facial growth in these patients. As restriction to facial development can have significant implications to form, function, and psychological well-being, practitioners should have an appreciation for the effects of the different cleft therapies to facial growth. We have outlined and thoroughly reviewed in chronological order all of the interventions from birth to adulthood necessary in the comprehensive care of the patient with cleft lip and palate, along with the effects they may or may not have on facial growth.
PMID: 30882417
ISSN: 1536-3708
CID: 3734822