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Transforming the Degradation Rate of β-tricalcium Phosphate Bone Replacement Using 3-Dimensional Printing

Shen, Chen; Wang, Maxime M; Witek, Lukasz; Tovar, Nick; Cronstein, Bruce N; Torroni, Andrea; Flores, Roberto L; Coelho, Paulo G
BACKGROUND:β-Tricalcium phosphate (β-TCP) is one of the most common synthetic bone grafting materials utilized in craniofacial reconstruction; however, it is limited by a slow degradation rate. The aim of this study was to leverage 3-dimensional (3D) printing in an effort to accelerate the degradation kinetics of β-TCP. METHODS:Twenty-two 1-month-old New Zealand white rabbits underwent creation of calvarial and alveolar defects, repaired with 3D-printed β-TCP scaffolds coated with 1000 μM of osteogenic agent dipyridamole. Rabbits were euthanized after 2, 6, and 18 months after surgical intervention. Bone regeneration, scaffold degradation, and bone mechanical properties were quantified. RESULTS:Histological analysis confirmed the generation of vascularized and organized bone. Microcomputed tomography analysis from 2 to 18 months demonstrated decreased scaffold volume within calvarial (23.6% ± 2.5%, 5.1% ± 2.2%; P < 0.001) and alveolar (21.5% ± 2.2%, 0.2% ± 1.9%; P < 0.001) defects, with degradation rates of 54.6%/year and 90.5%/year, respectively. Scaffold-inducted bone generation within the defect was volumetrically similar to native bone in the calvarium (55.7% ± 6.9% vs 46.7% ± 6.8%; P = 0.064) and alveolus (31.4% ± 7.1% vs 33.8% ± 3.7%; P = 0.337). Mechanical properties between regenerated and native bone were similar. CONCLUSIONS:Our study demonstrates an improved degradation profile and replacement of absorbed β-TCP with vascularized, organized bone through 3D printing and addition of an osteogenic agent. This novel additive manufacturing and tissue engineering protocol has implications to the future of craniofacial skeletal reconstruction as a safe and efficacious bone tissue engineering method.
PMCID:8616850
PMID: 34611100
ISSN: 1536-3708
CID: 5072082

Three-Dimensionally-Printed Bioactive Ceramic Scaffolds: Construct Effects on Bone Regeneration

Fama, Christopher; Kaye, Gabriel J; Flores, Roberto; Lopez, Christopher D; Bekisz, Jonathan M; Torroni, Andrea; Tovar, Nick; Coelho, Paulo G; Witek, Lukasz
BACKGROUND/PURPOSE/OBJECTIVE:The utilization of three-dimensionally (3D)-printed bioceramic scaffolds composed of beta-tricalcium phosphate in conjunction with dipyridamole have shown to be effective in the osteogenesis of critical bone defects in both skeletally immature and mature animals. Furthermore, previous studies have proven the dura and pericranium's osteogenic capacity in the presence of 3D-printed scaffolds; however, the effect galea aponeurotica on osteogenesis in the presence of 3D scaffolds remains unclear. METHOD/DESCRIPTION/UNASSIGNED:Critical-sized (11 mm) bilateral calvarial defects were created in 35-day old rabbits (n = 7). Two different 3D scaffolds were created, with one side of the calvaria being treated with a solid nonporous cap and the other with a fully porous cap. The solid cap feature was designed with the intention of preventing communication of the galea and the ossification site, while the porous cap permitted such communication. The rabbits were euthanized 8 weeks postoperatively. Calvaria were analyzed using microcomputed tomography, 3D reconstruction, and nondecalcified histologic sectioning in order assess differences in bone growth between the two types of scaffolding. RESULTS:Scaffolds with the solid (nonporous) cap yielded greater percent bone volume (P = 0.012) as well as a greater percent potential bone (P = 0.001) compared with the scaffolds with a porous cap. The scaffolds with porous caps also exhibited a greater percent volume of soft tissue (P < 0.001) presence. There were no statistically significant differences detected in scaffold volume. CONCLUSION/CONCLUSIONS:A physical barrier preventing the interaction of the galea aponeurotica with the scaffold leads to significantly increased calvarial bone regeneration in comparison with the scaffolds allowing for this interaction. The galea's interaction also leads to more soft tissue growth hindering the in growth of bone in the porous-cap scaffolds.
PMID: 33003153
ISSN: 1536-3732
CID: 5050092

Advantages and disadvantages of mandibular distraction in Robin sequence

Breugem, Corstiaan C; Logjes, Robrecht J H; Nolte, Jitske W; Flores, Roberto L
Robin sequence (RS) is diagnosed in infants born with micrognathia, glossoptosis and varying degrees of upper airway obstruction (UAO). Due to the variable levels of hypoxia, severe breathing and feeding problems can occur. Treatment is determined by clinical severity, ranging from conservative interventions for mild cases to surgical interventions for severe cases. Mandibular distraction osteogenesis (MDO) is a surgical technique that gradually lengthens the mandible after an osteotomy by using an internal or external distraction device, directly correcting the micrognathia. This review will focus on advantages and disadvantages of mandibular distraction in infants with RS.
PMID: 34663561
ISSN: 1878-0946
CID: 5043162

The Surgical Treatment of Robin Sequence: Neonatal Mandibular Distraction Osteogenesis in the Unfavorable Patient

Shen, Chen; Wang, Maxime M; Eisemann, Bradley T; Rodriguez, Alcibiades J; Rickert, Scott M; Flores, Roberto L
INTRODUCTION/BACKGROUND:Neonates with severe Pierre Robin sequence (PRS) can be treated by mandibular distraction osteogenesis (MDO), tongue-lip adhesion, or tracheostomy; however, there is an active debate regarding the indications of MDO in this patient population. Published algorithms identify tracheomalacia, bronchomalacia, laryngomalacia, hypotonic syndromes, and central sleep apnea as contraindications for MDO and indications for tracheostomy, but these comorbidities may exist along a spectrum of severity. The authors propose that appropriately selected neonates with PRS who concurrently express 1 or more of these traditional contraindications may be successfully treated with MDO. METHODS:The authors performed a 5-year retrospective chart review of all neonates who underwent MDO for treatment of severe PRS. All patients expressed a comorbidity previously identified as an indication for tracheostomy. Pre- and postoperative characteristics were recorded. Apnea/hypopnea index (AHI) before and after MDO were compared using 2-tailed repeated measures t-test. RESULTS:The authors identified 12 patients with severe PRS and conditions associated with contraindications to MDO: 9 (75.0%) patients had laryngomalacia, 6 (50.0%) patients had tracheomalacia, 2 (16.6%) patients had bronchomalacia, 1 (8.3%) patient had central sleep apnea, and 3 (25.0%) patients had hypotonia. Five (41.7%) patients underwent concurrent gastrostomy tube placement due to feeding insufficiency. Average birthweight was 3.0 kg. Average pre-op AHI was 34.8. Average post-op AHI was 7.3. All patients successfully underwent MDO with avoidance of tracheostomy. CONCLUSIONS:By employing an interdisciplinary evaluation of patient candidacy, MDO can safely and effectively treat upper airway obstruction and avoid tracheostomy in higher-risk neonatal patients with traditional indications for tracheostomy.
PMID: 34705382
ISSN: 1536-3732
CID: 5038922

Perceived Barriers to Comprehensive Cleft Care Delivery: Results From A Capacity-Building Educational Initiative and Implications

Kantar, Rami S; Breugem, Corstiaan C; Alfonso, Allyson R; Keith, Kristen; Kassam, Serena; Annan, Beyhan; Chahine, Elsa M; Wasicek, Philip J; Patel, Krishna G; Flores, Roberto L; Hamdan, Usama S
INTRODUCTION:We analyzed the perceptions of participants and faculty members in simulation-based comprehensive cleft care workshops regarding comprehensive cleft care delivery in developing countries. METHODS:Data were collected from participants and faculty members in 2 simulation-based comprehensive cleft care workshops organized by Global Smile Foundation. We collected demographic data and surveyed what they believed was the most significant barrier to comprehensive cleft care delivery and the most important intervention to deliver comprehensive cleft care in developing countries. We also compared participant and faculty responses. RESULTS:The total number of participants and faculty members was 313 from 44 countries. The response rate was 57.8%. The majority reported that the most significant barrier facing the delivery of comprehensive cleft care in developing countries was financial (35.0%), followed by the absence of multidisciplinary cleft teams (30.8%). The majority reported that the most important intervention to deliver comprehensive cleft care was creating multidisciplinary cleft teams (32.2%), followed by providing cleft training (22.6%). We found no significant differences in what participants and faculty perceived as the greatest barrier to comprehensive cleft care delivery (P = 0.46), or most important intervention to deliver comprehensive cleft care in developing countries (P = 0.38). CONCLUSIONS:Our study provides an appraisal of barriers facing comprehensive cleft care delivery and interventions required to overcome these barriers in developing countries. Future studies will be critical to validate or refute our findings, as well as determine country-specific roadmaps for delivering comprehensive cleft care to those who need it the most.
PMID: 34253700
ISSN: 1536-3708
CID: 4968782

Double Frost Suture Technique for Simultaneous Skin Grafting of the Upper and Lower Eyelids

DeMaria, Lauren N; Tran, Ann Q; Tooley, Andrea A; North, Victoria S; Flores, Roberto L; Lisman, Richard D; Belinsky, Irina
The double Frost suture is a useful supplement to the reconstruction of ipsilateral upper and lower eyelid defects with full-thickness skin grafts. This technique involves silk traction sutures that overlap the upper and lower eyelids to place them on maximal stretch after placement of 2 full-thickness skin grafts. It has the added benefit of protecting the cornea and compressing both grafts under 1 bolster. The authors illustrate this technique in 2 pediatric cases-a congenital melanocytic kissing eyelid nevus and a periocular burn. Each case resulted in large upper and lower anterior lamellar defects, which were reconstructed with supraclavicular and retroauricular free skin grafts. The double Frost sutures counter vertical cicatricial forces during graft healing, obviating the need for staged procedures. Both described cases resulted in excellent graft survival with minimal contracture.
PMID: 34297708
ISSN: 1537-2677
CID: 4948712

Skeletal and Dental Stability Following Different Magnitude of Le Fort I Advancement in Patients With Cleft Lip and Palate

Wangsrimongkol, Buddhathida; Flores, Roberto L; Staffenberg, David A; Rodriguez, Eduardo D; Shetye, Pradip R
PURPOSE/OBJECTIVE:The purpose of this study was to measure the association between the magnitude of advancement and dental and skeletal relapse in patients with cleft lip and palate (CLP). METHODS:A single-institution retrospective cohort study of skeletally matured patients with CLP who underwent isolated Le Fort I advancement surgery between 2013 and 2019 was studied. Patients were included if they had lateral cephalograms or cone-beam computed tomography (CBCT) at preoperative (T1), immediately postoperative (T2), and 1-year follow-up (T3). Lateral cephalometric landmarks were digitized and measured. The sample was divided on the basis of the magnitude of skeletal advancement: minor (<5 mm), moderate (≥5 but <10 mm), and major (≥10 mm) advancement groups. The mean advancement and relapse were compared between groups using 1-way ANOVA. Correlation between the amount of surgical advancement and relapse was evaluated. RESULTS:Forty-nine patients with nonsyndromic CLP with hypoplastic maxilla met inclusion criteria and the sample consisted of 36 males and 13 females with the mean age of 19.5 years. In the minor, moderate, and major advancement groups, the mean advancement at point A was +4.1 ± 0.4, + 7.5 ± 1.4, and +11.3 ± 1.3 mm, respectively. At 1-year follow-up, the mean relapse at point A was -1.3 ± 1.2, -1.1 ± 1.2, and -1.7 ± 1.5 mm, respectively. There was no significant difference in the relapse amount between all surgical groups. No correlation between the magnitude of advancement and relapse was found. CONCLUSIONS:This study demonstrated no statistically significant difference in skeletal stability between a minor (<5 mm), moderate (≥5 but <10 mm), and major (≥10 mm) Le Fort I advancement groups in patients with clefts. Regardless of the degree of advancement, mild skeletal relapse was observed in all 3 groups.
PMID: 34153247
ISSN: 1531-5053
CID: 4918192

Simulation-based comprehensive cleft care workshops: A reproducible model for sustainable education [Meeting Abstract]

Melhem, A; Al, Abyad O; Chahine, E; Breugem, C; Keith, K; Kassam, S; Vijayakumar, C; Bow, M; Alfonso, A; Esenlik, E; Patel, K; Shetye, P; Santiago, P; Losee, J; Steinbacher, D; Kummer, A; Flores, R; Rossell-Perry, P; Garib, D; Alonso, N; Mann, R; Pamplona, M; Giugliano, C; Prada-Madrid, J R; Padwa, B; Raposo-Amaral, C -E; Sommerlad, B; Tse, R; Bennun, R; Collares, M; Kantar, R; Hamdan, U
Background/Purpose: Newborns with cleft lip and/or palate (CLP) exceed 100 000 per year in low- and middle-income countries (LMICs). Patients, if left untreated, are at high risk of morbidity, due to functional deficits, malnutrition, aspiration, and infections. Limited resources in LMICs create barriers for establishing Interdisciplinary Cleft Care programs. Surgical missions driven by nonprofit organizations have been able to partially address this need, but their ability to promote long-term sustainable cleft care has come to a question. Simulation-based training has emerged as an essential tool for enhancing medical education and training. Global Smile Foundation, a nonprofit organization, is a leader in the establishment of Interdisciplinary Cleft Care programs, with its volunteers being involved in cleft care for over 3 decades. We were able to demonstrate the efficacy of our first Simulation-Based Comprehensive Cleft Care Workshop (SBCCW), in the Middle East-North Africa (MENA) region, and its wide acceptance by our recipients. In the current study, we want to prove the effectiveness and successfulness of our second SBCCW, in Latin America. Methods/Description: Our second SBCCW took place in Lima, Peru, in October 2019. Hands-on simulations of CLP repair using highfidelity CLP simulators were also provided to our participants. Participants were asked to complete a satisfaction survey at the end. Attendees were also asked about the obstacles facing cleft care in their countries and the possible interventions to overcome these obstacles. Short-term (at the end of the SBCCW) and medium-term (6 months later) follow ups were conducted by our team collecting data about improvements in the participants' competence, performance, outcomes, clinical care, and whether the SBCCW has changed their practice. Procedural confidence for pre- and postsimulation was evaluated using the psychometrically validated tool for measuring selfconfidence during surgical learning. Descriptive statistics were used for the collected data. Data analyses were performed using the Statistical Package for the Social Sciences. XXResult(s): Ninety-eight of the 198 participants from 29 different countries filled the satisfaction survey at the end of the workshop. The 2 most common barriers to cleft care in LMICs identified by our participants are the absence of financial support and the absence of multidisciplinary teams. Respondents claimed an improvement in their procedural confidence after the simulation sessions. Respondents had consistent short-term and medium-term impressions about the SBCCW positively impacting their competence, performance, outcomes, clinical care, and even changing their practice. XXConclusion(s): This study provides evidence that implementation of a SBCCW leads to a significantly improved procedural confidence, as well as a sustained positive impact on the clinical practice of the participants, reinforcing its role as a cleft care capacity-building tool
EMBASE:635187570
ISSN: 1545-1569
CID: 4911892

A computer-based simulator for the study of unilateral cleft lip repair [Meeting Abstract]

Cutting, C; Sifakis, E; Wang, Q; Tao, Y; Flores, R
Background/Purpose: For the past 25 years computer-based simulation of cleft lip repair has been an elusive goal. To date, interactive 3D models have allowed students to make preoperative incision markings. Animation generated blend shapes allow premodeled surgical animations to be played back in 3D video game format. Neither of these efforts allow the student to actually perform his/her own lip repair. This article presents what we believe to be the first cleft lip simulator to allow the student to prospectively do complete cleft lip/ nose corrections. Historical procedures and proposed new ones can be performed. A deeper level of understanding can be obtained using this cognitive experiential approach without injuring a real patient. Methods/Description: A 3D solid model of a complete unilateral cleft lip/nose has been prepared based on a laser scan of an actual patient. Procedures are performed using a surgical toolkit consisting of (1) skin hooks, (2) skin/mucosa scalpel, (3) skin and periosteal undermine tool, (4) deep cut tool for cutting through muscle, fat, and cartilage, and (5) a suture tool. First order biologically accurate physics are provided by modeling the solids as a half million tetrahedra. Projective dynamics are used to implement biphasic tissue behavior in which at low strain Hooke's law elasticity is provided, but as strain exceeds 14% the tissue becomes much stiffer to model the commonly observed the flap won't reach phenomenon. Collision is modeled between the teeth and bone of the maxilla and the undersurface of the lip using a Schur complement approach. Near real-time performance is provided on a laptop computer in 3D video game format. A history files may be recorded of the sequence of actions performed by the surgeon.
Result(s): A demonstration of the model and the surgical toolset will be performed in real time. A full cleft lip/nose repair using the simulator will be demonstrated using its history feature.
Conclusion(s): A first order biophysically accurate simulator of cleft lip and nose repair has been developed. It permits the student to cognitively explore different methods of repair and store his/her surgical sequence. This simulator has application in experiential education, proficiency testing, and the design of new surgical procedures
EMBASE:635187536
ISSN: 1545-1569
CID: 4909492

Craniofacial Distraction-The Thirty-Year Journey [Editorial]

Flores, Roberto L
PMID: 34051905
ISSN: 1558-0504
CID: 4898212