Development of a novel mandibular distraction osteogenesis simulator using Computer Aided Design and 3D printing.

INTRODUCTION: Micrognathia, a component of Robin Sequence, can cause glossoptosis, failure of palatal fusion, and critical obstruction of the airway. Mandibular distraction osteogenesis (MDO) is at times offered to anteriorly translate the mandible and tongue, relieving airway obstruction. MDO is an intricate reconstructive procedure that may be ideal for teaching using a high-fidelity educational simulator, allowing early hands-on experience in a zero-risk environment. OBJECTIVES: To design a novel, low-cost, high-fidelity neonatal MDO simulator that can be used for trainee education and refinement of surgical technique. METHODS: A novel MDO simulator was developed using additive manufacturing techniques. Three experts in MDO surgery completed a 20-item survey, rating the simulator's physical attributes, the realism of experience, the simulator's value, its relevance to practice and the surgeon's ability to perform tasks on a 4-point Likert scale. RESULTS: Computer Aided Design (CAD) and 3D printing allowed for the production of a realistic surgical simulator that emulates important aspects of MDO surgery. This preliminary evaluation indicated adequate means across the five domains relevant to the simulator's fidelity and usability (M = 3.33 to 3.75) out of a maximum of 4 points. Lowest rated items were consistent with expert comments allowing future refinement on subsequent iterations. Consumable material costs per model were $9.39 USD. CONCLUSIONS: The MDO model demonstrated adequate fidelity and holds promise as a skill-development tool for surgeons in training. Further studies are planned to determine its utility as a training and assessment tool.

Hybrid Three-Dimensional-Printed Ear Tissue Scaffold With Autologous Cartilage Mitigates Soft Tissue Complications.

OBJECTIVES/HYPOTHESIS: To analyze the use of highly translatable three-dimensional (3D)-printed auricular scaffolds with and without novel cartilage tissue inserts in a rodent model. STUDY DESIGN: Preclinical rodent animal model. METHODS: This prospective study assessed a single-stage 3D-printed auricular bioscaffold with or without porcine cartilage tissue inserts in an athymic rodent model. Digital Imaging and Communications in Medicine computed tomography images of a human auricle were segmented to create an external anatomic envelope filled with orthogonally interconnected spherical pores. Scaffolds with and without tissue inset sites were 3D printed by laser sintering bioresorbable polycaprolactone, then implanted subcutaneously in five rats for each group. RESULTS: Ten athymic rats were studied to a goal of 24 weeks postoperatively. Precise anatomic similarity and scaffold integrity were maintained in both scaffold conditions throughout experimentation with grossly visible tissue ingrowth and angiogenesis upon explantation. Cartilage-seeded scaffolds had relatively lower rates of nonsurgical site complications compared to unseeded scaffolds with relatively increased surgical site ulceration, though neither met statistical significance. Histology revealed robust soft tissue infiltration and vascularization in both seeded and unseeded scaffolds, and demonstrated impressive maintenance of viable cartilage in cartilage-seeded scaffolds. Radiology confirmed soft tissue infiltration in all scaffolds, and biomechanical modeling suggested amelioration of stress in scaffolds implanted with cartilage. CONCLUSIONS: A hybrid approach incorporating cartilage insets into 3D-printed bioscaffolds suggests enhanced clinical and histological outcomes. These data demonstrate the potential to integrate point-of-care tissue engineering techniques into 3D printing to generate alternatives to current reconstructive surgery techniques and avoid the demands of traditional tissue engineering. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1008-1015, 2021.

Treatment of severe porcine tracheomalacia with a 3-dimensionally printed, bioresorbable, external airway splint.

IMPORTANCE: The study demonstrates use of a novel intervention for severe tracheobronchomalacia (TBM). OBJECTIVE: To test a novel, 3-dimensionally (3D) printed, bioresorbable airway splint for efficacy in extending survival in a porcine model of severe, life-threatening TBM. DESIGN AND PARTICIPANTS: A randomized, prospective animal trial was used to evaluate an external airway splint as treatment of severe, life-threatening TBM in a multi-institutional, multidisciplinary collaboration between a biomedical engineering department and an academic animal surgery center. Six 2-month-old Yorkshire pigs underwent tracheal cartilage division and inner tracheal lumen dissociation and were randomly assigned to splint treatment (n = 3) or control groups (n = 3). Two additional pigs had the splint placed over their normal trachea. INTERVENTIONS: A 3D-printed, bioresorbable airway splint was assessed in a porcine animal model of life-threatening TBM. The open-cylindrical, bellow-shaped, porous polycaprolactone splint was placed externally and designed to suspend the underlying collapsed airway. Two additional animals were splinted without model creation. MAIN OUTCOMES AND MEASURES: The observer-based Westley Clinical Croup Scale was used to assess the clinical condition of animals postoperatively. Animal survival time was noted. RESULTS: Complete or nearly complete tracheal lumen collapse was observed in each animal, with resolution of symptoms in all of the experimental animals after splint placement. Using our severe TBM animal model, survival was significantly longer in the experimental group receiving the airway splint after model creation than in the control group (P = .0495). CONCLUSIONS AND RELEVANCE: A multidisciplinary effort producing a computer-aided designed, computer-aided manufactured bioresorbable tracheobronchial splint was tested in a porcine model of severe TBM and was found to extend survival time. Mortality in the splinted group was ascribed to the TBM model based on the lack of respiratory distress in splinted pigs, long-term survival in animals implanted with the splint without TBM, and necropsy findings.

GlycoPEGylation of recombinant therapeutic proteins produced in Escherichia coli.

Covalent attachment of polyethylene glycol, PEGylation, has been shown to prolong the half-life and enhance the pharmacodynamics of therapeutic proteins. Current methods for PEGylation, which rely on chemical conjugation through reactive groups on amino acids, often generate isoforms in which PEG is attached at sites that interfere with bioactivity. Here, we present a novel strategy for site-directed PEGylation using glycosyltransferases to attach PEG to O-glycans. The process involves enzymatic GalNAc glycosylation at specific serine and threonine residues in proteins expressed without glycosylation in Escherichia coli, followed by enzymatic transfer of sialic acid conjugated with PEG to the introduced GalNAc residues. The strategy was applied to three therapeutic polypeptides, granulocyte colony stimulating factor (G-CSF), interferon-alpha2b (IFN-alpha2b), and granulocyte/macrophage colony stimulating factor (GM-CSF), which are currently in clinical use.