Faculty Bibliography

In this work, the anodic current at an electrode grafted with a molecularly imprinted polymer (MIP) crosslinked via a combination of hydrophobic ethyleneglycol dimethacrylate (EDMA) and hydrophilic methylene bisacrylamide (MBAA) was found to exhibit enantioselective sensitivity to the phenylalanine template in aqueous solution. An MIP-grafted electrode crosslinked with a 2:1 mixture of EDMA and MBAA was observed to respond to the template with the highest enantioselectivity, such that the change in current induced by the imprinted template was more than four times that induced by the enantiomer of the template. The contact angle of a water droplet on an MIP-coated electrode prepared using the optimal crosslinker blending ratio was also sensitive to the template and again exhibited chiral selectivity. The change in the contact angle induced by the template was more than twice as large as that obtained from the template's enantiomer. Atomic force microscopy showed that the surface of the MIP layer fabricated using a mixture of crosslinkers was rougher than that made with a single crosslinking agent, although there was no apparent correlation between the roughness and the enantioselectivity of the layer. These results indicate that the appropriate combination of crosslinkers enables the chiral-selective gate effect by modulating the flexibility and hydrophilicity of the MIP layer. The approach described herein therefore represents a new means of improving the selectivity of MIPs by blending crosslinkers having different chemical properties.

Introduction: The purpose of this work was to (1) develop an in vivo murine model to study the influence of mechanical loading on bone regeneration, and (2) to use this model to determine the effects of loading on cellular events during repair. Early postoperative weight-bearing is an important aspect of orthopaedic rehabilitation, though its effects on cellular and molecular events in bone regeneration are not completely understood1. We describe a novel in vivo system consisting of a mechanically loaded, stable cortical defect injury in the mouse tibia, and present data showing the influence of early loading on proliferation and cellular differentiation. Methods: Bilateral mono-cortical tibial defects were created in B6 adult mice (n=40); this defect typically heals via intramembranous ossification2. Tibiae were subjected to 4 consecutive days of in vivo axial compressive loading (4 N, 2 Hz, 60 cycles)(Fig. 1A) beginning on post-surgical day (psd) 2. Non-loaded tibiae served as controls. In vivo muCT images of defects were acquired on days 2, 5, 8, 10, and 14. The ROI included the regenerate and surrounding cortices. Percent change in bone volume (%deltaBV) at each time point, relative to psd 2, was calculated for each tibia. Mice were euthanized on days 5, 10, and 14. Longitudinal sections were assessed for proliferation and differentiation. A linear elastic FE model at psd 2 was developed and strains were computed for a 4 N point load. Results: Highest compressive strains (700-1100 mue) were observed at the posteromedial edge of the defect, with strains reaching ~300 mue in tension at the anterior edge (Fig 1). %deltaBV was significantly lower in loaded versus control tibiae at psd 8 and 10 relative the first day of loading (psd 2) (Fig 2) by a T-test (alpha=0.05). Loaded defects displayed increased proliferation (Fig 3) and greater amounts of cartilage (Fig 4) at the periosteum and within the regenerate at psd 10 and 14. Conclusion: Low magnitude loading in the inflammatory phase (psd 2) delays mineralization and remodeling by prolonging the proliferative phase and initiating a robust endochondral response. The primary advantage of this model is that it combines a well-described and tightly regulated sequence of repair events with a highly controlled mechanical stimulus, a system amenable for studying effects of physical signals on distinct components of the regenerative cascade. Refs: 1. Betts and Muller, Front Endocrinol 2014. 2. Leucht et al., Bone 2007

With the advent of the microvascular fibula free flap (MVFFF), maxillofacial reconstruction following ablative surgery has been a viable solution for patients with large maxillary or mandibular defects. Furthermore, total maxillofacial reconstruction in a two-stage process, where the fibula is harvested and dental implants placed (Stage I) followed by ablative surgery, inset and immediate loading with a dental prosthesis (Stage 2) has been well documented.1 This procedure, however, requires two separate surgical procedures and a delay of at least 10 weeks between each stage where the patient is often left partially or completely edentulous. The incorporation of computer-aided surgical simulation (CASS) and computer-aided design/computer-aided manufacturing (CAD/CAM) has made it possible to not only complete total maxillofacial reconstruction from tumor ablationto immediate insertion of an implant-retained dental prosthesis in a single OR procedure, butithas also increased the predictability and accuracy of maxillofacial reconstruction and decreased intraoperative time.2 Patients requiring more complex maxillofacial reconstruction heavily benefit from increased precision of the final surgical outcome as the accuracy of each osteotomy influences subsequent steps. The aim of our study is to assess the predictability and accuracy of virtually planned, single-stage total maxillofacial reconstruction, also known as 'Jaw in a Day'.³ We conducted a retrospective chart review of all patients who underwent maxillofacial tumor ablation, MVFFF reconstruction, implant placement and immediate implant loading with a dental prosthesis in a single OR procedure. These procedures were completed at Bellevue Hospital Center and NYU Langone Medical Center from January 2011 to January 2015. All cases were virtually planned with Medical Modeling (Golden, CO), and stereolithographic models, osteotomy guides, implant guides, and dental prosthesis were fabricated via CAD/CAM technology. To determine the precision and accuracy of the post-surgical outcomes, we compared the final positions of the implants and fibula on postoperative CT imaging with the planned positions of the implants and fibula based on preoperative virtual planning with Medical Modeling. A total of 8 patients underwent tumor ablation, MVFFF reconstruction, implant placement and immediateimplant loading with a dental prosthesis in a single OR procedure. All patients were diagnosed with benign mandibular (7) and maxillary (1) tumors, including ameloblastoma (6), odontogenic myxoma (1), and AVmalformation (1).Atotal of 35implants were placed with satisfactory primary stability at the time of surgery. On average, the final positions of the implants placed were within 2mm of the virtually treatment planned positions within the fibula. To date, there have been no flap failures and only one implant has failed osseointegration into the MVFFF. Total maxillofacial reconstruction via CASS and CAD/CAM technology has made it possible for surgeons to complete these procedures with high precision and accuracy while minimizing intraoperative time. Additionally, immediate dental rehabilitation is possible at the time of ablation, eliminating the period of edentulism for these patients. Given the highly predictable and accurate postoperative outcomes and low complications rates of virtually planned total maxillofacial reconstruction with a MVFFF and immediate dental rehabilitation, this technique is quickly becoming the standard of care for patients requiring complex maxillofacial reconstruction

Reconstruction of large maxillary and mandibular defects following ablative surgery has posed a challenge to the head and neck surgeon due to the high functional and esthetic demands requiring precise three-dimensional reconstruction. Previous issues with maxillofacial reconstruction have included poor facial contour, unfavorable orthognathic relationships, and inability to provide adequate dental rehabilitation. The advent of the fibula flap along with (3D) facial analysis and virtual surgical simulation has revolutionized surgical interventions of the head and neck. Recent reports on the long-term success of dental implants in fibula reconstructions have made dental rehabilitation a reality. However, the loading and restoration of these implants are usually delayed prior to final prosthodontic rehabilitation leading to adverse functional, esthetic and psychological effects. Rohner et al. has documented the success of a two-stage surgery of fibula harvest and dental implant placement (Stage 1) followed by ablative surgery, inset and immediate loading with a dental prosthesis (Stage 2)⁽²⁾; this procedure is a two stage process that involves a 10-week delay between each surgery and will leave the patient edentulous. At our institution, computer-aided surgery and CAD/CAM technologies have enabled us to virtually plan complex surgery and have afforded our group the opportunity of providing a "Jaw in a Day '¹ This technique is a one-stage complete surgery including ablation, free flap, implant, and prosthetic reconstruction. A retrospective chart review was conducted for all patients who received immediate dental implants with a dental prosthesis in a fibular free flap following mandibular resection due to benign tumors. "Jaw in a Day 'procedures were completed at two of our affiliated hospitals (Bellevue Hospital Center and NYU Langone Medical Center) from January 2011 to January 2015. We looked at success rate of flaps, implants, and prostheses. We also looked at primary and long-term complications. Of the 8 patients who underwent the above procedure, a total of 35 immediate implants were placed along with a fixed prosthesis. Patients received maxillary/mandibular resection, fibula free flap reconstruction with immediate implant and dental prosthesis placement. All patients treated were diagnosed with benign mandibular (7) and maxillary (1) tumors, including ameloblastoma (6), odontogenic myxoma (1), and AV malformation (1). Of the 35 implants placed, 1 implant failed and was removed. The cumulative survival of fibular-free flaps was 100%. The cumulative implant success rate was 97%. Complications included soft tissue perimplantitis (2), plate exposure (2), and (1) prosthesis that did not adequately fit. The followup of the 8 patients was from January 2011 to January 2015. Single-stage maxillofacial reconstruction with virtual surgical planning has greatly impacted the field of maxillofacial reconstruction allowing for precision and accuracy while improving patient's function and quality of life. The above study shows its feasibility and low complication rates. Immediate implant and dental prosthesis placement has helped reduce the time for dental prosthetic rehabilitation and avoid the traditional 3- to 6-month delay period. Reconstruction with a MVFFF and immediate dental rehabilitation has revolutionized the treatment of benign tumor following ablative surgery

The genome sequencing and the development of RNAi knockdown technologies in the urochordate Oikopleura dioica are making this organism an attractive emergent model in the field of EvoDevo. To succeed as a new animal model, however, an organism needs to be easily and affordably cultured in the laboratory. Nowadays, there are only two facilities in the world capable to indefinitely maintain Oikopleura dioica, one in the SARS institute (Bergen, Norway) and the other in the Osaka University (Japan). Here, we describe the setup of a new facility in the University of Barcelona (Spain) in which we have modified previously published husbandry protocols to optimize the weekly production of thousands of embryos and hundreds of mature animals using the minimum amount of space, human resources, and technical equipment. This optimization includes novel protocols of cryopreservation and solid cultures for long-term maintenance of microalgal stocks-Chaetoceros calcitrans, Isochrysis sp., Rhinomonas reticulate, and Synechococcus sp.-needed for Oikopleura dioica feeding. Our culture system maintains partially inbred lines healthy with similar characteristics to wild animals, and it is easily expandable to satisfy on demand the needs of any laboratory that may wish to use Oikopleura dioica as a model organism.

The assessment, diagnosis, and management of fractures, particularly fractures that exhibit delayed healing, present considerable unique challenges to both patients and physicians. Fracture healing results from a complex series of biochemical events that may produce complete restoration of the anatomic and biochemical properties of the original osseous tissue. Fracture healing requires appropriate reduction, mechanical stability, and adequate vascularity to the fracture site; compromise of one of these elements may lead to delayed healing or nonunion. The patient's history, physical examination, and findings based on radiographs or other imaging modalities allow for assessment and characterization of the progression of healing. If nonunion is recognized, it is important for the clinician to understand the current treatment options that are available to optimize healing. Physical stimulation therapies include electromagnetic stimulation and low-intensity pulsed ultrasonography. Osteogenic factors used locally to promote fracture healing include autologous bone marrow and peptide signaling molecules such as platelet-derived growth factors, fibroblast growth factors, and bone morphogenetic proteins. Systemic biological protein such as parathyroid hormone and factors that target the Wnt family of signaling molecules offers promising data regarding its abilities to promote healing. Large segmental defects must be managed depending on the type and severity of the injury and may require treatment with bone grafts, induced membrane techniques, acute shortening, or distraction osteogenesis. A systematic approach in evaluating fracture union and an understanding of the modern methods to promote fracture healing will allow clinicians to significantly improve the treatment of patients with these injuries.