Biodegradation Behavior Control for Shape Memory Polyester Poly(Glycerol-Dodecanoate): An In Vivo and In Vitro Study.

Poly(glycerol-dodecanoate) (PGD) has garnered increasing attention in biomedical engineering for its degradability, shape memory, and rubber-like mechanical properties. Adjustable degradation is important for biodegradable implants and is affected by various aspects, including material properties, mechanical environments, temperature, pH, and enzyme catalysis. The crosslinking and chain length characteristics of poly(lactic acid) and poly(caprolactone) have been widely used to adjust the in vivo degradation rate. The PGD degradation rate is affected by its crosslink density in in vitro hydrolysis; however, there is no difference in vivo. We believe that this phenomenon is caused by the differences in enzymatic conditions in vitro and in vivo. In this study, it is found that the degradation products of PGD with different molar ratios of hydroxyl and carboxyl (MRH/C) exhibit varied pH values, affecting the enzyme activity and thus achieving different degradation rates. The in vivo degradation of PGD is characterized by surface erosion, and its mass decreases linearly with degradation duration. The degradation duration of PGD is linearly extrapolated from 9-18 weeks when MRH/C is in the range of 2.00-0.75, providing a protocol for adjusting the degradation durations of subsequent implants made by PGD.

Computational modeling of airway instability and collapse in tracheomalacia.

BACKGROUND: Tracheomalacia (TM) is a condition of excessive tracheal collapse during exhalation. Both acquired and congenital forms of TM are believed to result from morphological changes in cartilaginous, fibrous and/or smooth muscle tissues reducing airway mechanical properties to a degree that precipitates collapse. However, neither the specific amount of mechanical property reduction nor the malacic segment lengths leading to life threatening airway collapse in TM are known. Furthermore, the specific mechanism of collapse is still debated. METHODS: Computational nonlinear finite element models were developed to determine the effect of malacic segment length, tracheal diameter, and reduction in tissue nonlinear elastic properties on the risk for and mechanism of airway collapse. Cartilage, fibrous tissue, and smooth muscle nonlinear elastic properties were fit to experimental data from preterm lambs from the literature. These elastic properties were systematically reduced in the model to simulate TM. RESULTS: An intriguing finding was that sudden mechanical instability leading to complete airway collapse occurred in airways when even a 1 cm segment of cartilage and fibrous tissue properties had a critical reduction in material properties. In general, increased tracheal diameter, increased malacic segment length coupled with decreased nonlinear anterior cartilage/fibrous tissue nonlinear mechanical properties increased the risk of sudden airway collapse from snap through instability. CONCLUSION: Modeling results support snap through instability as the mechanism for life threatening tracheomalacia specifically when cartilage ring nonlinear properties are reduced to a range between fibrous tissue nonlinear elastic properties (for larger diameter airways > 10 mm) to mucosa properties (for smaller diameter airways < 6 mm). Although reducing posterior tracheal smooth muscle properties to mucosa properties decreased exhalation area, no sudden instability leading to collapse was seen in these models.

Comparison of reconstructive procedures for glenoid bone loss associated with recurrent anterior shoulder instability.

HYPOTHESIS: A tibial plafond allograft, iliac crest allograft, and coracoid autograft in a congruent arc Latarjet reconstruction better restore radius of curvature, depth, and surface area for glenoid bone loss in recurrent instability compared with the coracoid autograft in a standard Latarjet reconstruction for anteroinferior glenoid bone loss of the shoulder. METHODS: Three-dimensional shoulder models were generated from bilateral computed tomography scans in 15 patients, who were a mean (standard deviation [SD]) age of 23 (7.7) years, with recurrent anterior shoulder instability and known glenoid bone loss. The surface areas of the glenoid in the involved and contralateral normal shoulder were measured. Virtual surgery was then performed using standard and congruent arc Latarjet reconstruction, tibial plafond, and iliac crest allografts. Grafts were optimally positioned to restore articular congruity and defect fill. Radius of curvature and restoration of glenoid depth were compared with the contralateral glenoid. RESULTS: Glenoid surface area (11.04% [6.95% SD]) and depth (0.75 [0.57 SD] vs 1.44 [0.65 SD] mm) were significantly reduced (P < .012) in the injured glenoid. The mean (SD) coronal plane radius of curvature of the congruent arc Latarjet reconstruction (60.3 [39.0 SD] mm) more closely matched the radius of curvature of the injured glenoid (67.5 [33.2 SD] mm) compared with the other grafts. Restored glenoid depth was greater in the tibial plafond (1.8 [1.1 SD] mm) and iliac crest (2.0 [0.6 SD] mm) allografts compared with other grafts (P < .002). CONCLUSION: Congruent arc Latarjet reconstruction more closely restores native glenoid coronal radius of curvature, whereas tibial plafond and iliac crest allografts more adequately restore depth compared with standard Latarjet reconstruction.

Development and Characterization of Heparin-Containing Hydrogel/3D-Printed Scaffold Composites for Craniofacial Reconstruction.

Regeneration of cartilage and bone tissues remains challenging in tissue engineering due to their complex structures, and the need for both mechanical support and delivery of biological repair stimuli. Therefore, the goal of this study was to develop a composite scaffold platform for anatomic chondral and osteochondral repair using heparin-based hydrogels to deliver small molecules within 3D-printed porous scaffolds that provide structure, stiffness, and controlled biologic delivery. We designed a mold-injection system to combine hydrolytically degradable hydrogels and 3D-printed scaffolds that could be employed rapidly (< 30 min) in operating room settings (~23 °C). Micro-CT analysis demonstrated the effectiveness of our injection system through homogeneously distributed hydrogel within the pores of the scaffolds. Hydrogels and composite scaffolds exhibited efficient loading (~94%) of a small positively charged heparin-binding molecule (crystal violet) with sustained release over 14 days and showed high viability of encapsulated porcine chondrocytes over 7 days. Compression testing demonstrated nonlinear viscoelastic behavior where tangent stiffness decreased with scaffold porosity (porous scaffold tangent stiffness: 70%: 4.9 MPa, 80%: 1.5 MPa, and 90%: 0.20 MPa) but relaxation was not affected. Lower-porosity scaffolds (70%) showed stiffness similar to lower ranges of trabecular bone (4-8 MPa) while higher-porosity scaffolds (80% and 90%) showed stiffness similar to auricular cartilage (0.16-2 MPa). Ultimately, this rapid composite scaffold fabrication method may be employed in the operating room and utilized to control biologic delivery within load-bearing scaffolds.

3D printing modality effect: Distinct printing outcomes dependent on selective laser sintering (SLS) and melt extrusion.

A direct and comprehensive comparative study on different 3D printing modalities was performed. We employed two representative 3D printing modalities, laser- and extrusion-based, which are currently used to produce patient-specific medical implants for clinical translation, to assess how these two different 3D printing modalities affect printing outcomes. The same solid and porous constructs were created from the same biomaterial, a blend of 96% poly-ε-caprolactone (PCL) and 4% hydroxyapatite (HA), using two different 3D printing modalities. Constructs were analyzed to assess their printing characteristics, including morphological, mechanical, and biological properties. We also performed an in vitro accelerated degradation study to compare their degradation behaviors. Despite the same input material, the 3D constructs created from different 3D printing modalities showed distinct differences in morphology, surface roughness and internal void fraction, which resulted in different mechanical properties and cell responses. In addition, the constructs exhibited different degradation rates depending on the 3D printing modalities. Given that each 3D printing modality has inherent characteristics that impact printing outcomes and ultimately implant performance, understanding the characteristics is crucial in selecting the 3D printing modality to create reliable biomedical implants.

Porous biodegradable lumbar interbody fusion cage design and fabrication using integrated global-local topology optimization with laser sintering.

Biodegradable cages have received increasing attention for their use in spinal procedures involving interbody fusion to resolve complications associated with the use of nondegradable cages, such as stress shielding and long-term foreign body reaction. However, the relatively weak initial material strength compared to permanent materials and subsequent reduction due to degradation may be problematic. To design a porous biodegradable interbody fusion cage for a preclinical large animal study that can withstand physiological loads while possessing sufficient interconnected porosity for bony bridging and fusion, we developed a multiscale topology optimization technique. Topology optimization at the macroscopic scale provides optimal structural layout that ensures mechanical strength, while optimally designed microstructures, which replace the macroscopic material layout, ensure maximum permeability. Optimally designed cages were fabricated using solid, freeform fabrication of poly(ε-caprolactone) mixed with hydroxyapatite. Compression tests revealed that the yield strength of optimized fusion cages was two times that of typical human lumbar spine loads. Computational analysis further confirmed the mechanical integrity within the human lumbar spine, although the pore structure locally underwent higher stress than yield stress. This optimization technique may be utilized to balance the complex requirements of load-bearing, stress shielding, and interconnected porosity when using biodegradable materials for fusion cages.

Anatomic considerations of transclavicular-transcoracoid drilling for coracoclavicular ligament reconstruction.

HYPOTHESIS: Acromioclavicular (AC) joint injuries vary in severity and damage to the AC and coracoclavicular (CC) ligaments. We hypothesized that transclavicular-transcoracoid drilling techniques, which allow for arthroscopic passage and fixation of tendon grafts in bone sockets to replace the insufficient conoid and trapezoid ligaments, cannot restore the footprints of the conoid and trapezoid ligaments without significant risk of cortical breach and coracoid fracture. MATERIALS AND METHODS: Data from a prospective computed tomography shoulder registry were used to create 23 distinct shoulders. Three-dimensional models were constructed the shoulders in which virtual CC ligament reconstruction tunnels were superimposed using previously described anatomic distances and landmarks. RESULTS: Transclavicular-transcoracoid techniques resulted in mean remaining medial and lateral wall thicknesses before cortical breach of 7.3 ± 1.7 and 7.0 ± 1.6 mm, respectively. The distance from the entry point of this tunnel from the anatomic midpoint of the CC ligaments was 9.9 ± 2.2 mm. Attempts to recapitulate the CC ligament anatomy by using anatomic distances and landmarks with transcoracoid, transclavicular techniques resulted in medial cortical breach of the coracoid in 91.3% of the shoulders. CONCLUSION: Transclavicular-transcoracoid reconstructive techniques cannot restore the footprints of the conoid and trapezoid ligaments without significant risk of cortical breach and fracture. Attempts to correct this nonanatomic configuration by creating a tunnel based on the anatomic footprints results in a nearly universal medial cortical breach of the coracoid process.

Innovative design of minimal invasive biodegradable poly(glycerol-dodecanoate) nucleus pulposus scaffold with function regeneration.

Minimally invasive biodegradable implants with regeneration have been a frontier trend in clinic. Degeneration of nucleus pulposus (NP) is irreversible in most of spine diseases, and traditional spinal fusion or discectomy usually injure adjacent segments. Here, an innovative minimally invasive biodegradable NP scaffold with function regeneration inspired by cucumber tendril is developed using shape memory polymer poly(glycerol-dodecanoate) (PGD), whose mechanical property is controlled to the similar with human NP by adjusting synthetic parameters. The chemokine stromal cell-derived factor-1α (SDF-1α) is immobilized to the scaffold recruiting autologous stem cells from peripheral tissue, which has better ability of maintaining disc height, recruiting autologous stem cells, and inducing regeneration of NP in vivo compared to PGD without chemokine group and hydrogel groups significantly. It provides an innovative way to design minimally invasive implants with biodegradation and functional recovery, especially for irreversible tissue injury, including NP, cartilage and so on.

Sterilization effects on poly(glycerol dodecanedioate): A biodegradable shape memory elastomer for biomedical applications.

Biodegradable shape memory polymers provide unique regenerative medicine approaches in minimally invasive surgeries. Once heated, thermally responsive shape memory polymer devices can be compressed, programmed to fit within a small profile, delivered in the cold programmed state, and expanded when heated to body temperature. We have previously developed a biodegradable shape memory elastomer (SME), poly(glycerol dodecanedioate) (PGD), with transition temperatures near 37°C exhibiting nonlinear elastic properties like numerous soft tissues. Using SMEs in the clinic requires disinfection and sterilization methods that conserve physiochemical, thermomechanical, and shape recovery properties. We evaluated disinfection protocols using 70% ethanol and UV254 nm for research applications and ethylene oxide (EtO) gas sterilization for clinical applications. Samples disinfected with ethanol for 0.5 and 1 min showed no changes in physiochemical material properties, but after 15 min showed slower recovery rates than controls (p < .05). EtO sterilization at 54.4°C decreased transition temperatures and shape recovery rate compared to EtO sterilization at 37.8°C (p < .01) and controls (p < .05). Aging samples for 9 months in a vacuum desiccator significantly reduced shape recovery, and the recovery rate in EtO sterilized samples compared to controls (p < .001). Cytotoxicity testing (ISO-10993.5C:2012) revealed media extractions from EtO sterilized samples, sterilized at 37.8°C, and high-density polyethylene negative control samples exhibit lower cytotoxicity (IC50) than Ethanol 1 min, UV 2 h, and EtO 54.4°C. Cell viability of NIH3T3 fibroblasts on sterilized surfaces was equivalent on EtO 37.7°C, EtO 54.4°C and Ethanol sterilized substrates. Finally, chromogenic bacterial endotoxin testing showed endotoxin levels were below the FDA prescribed levels for devices contacting blood and lymphatic tissues for ethanol 1 min, UV 120 min, EtO 37.7°C, EtO 54.4°C. These findings outline various disinfection and sterilization processes for research and pre-clinical application and provide a pathway for developing custom sterilization cycles for the translation of biomedical devices utilizing PGD shape memory polymers.

Percutaneous delivery and degradation of a shape memory elastomer poly(glycerol dodecanedioate) in porcine pulmonary arteries.

Shape memory biodegradable elastomers are an emergent class of biomaterials well-suited for percutaneous cardiovascular repair requiring nonlinear elastic materials with facile handling. We have previously developed a chemically crosslinked shape memory elastomer, poly (glycerol dodecanedioate) (PGD), exhibiting tunable transition temperatures around body temperature (34-38 °C), exhibiting nonlinear elastic properties approximating cardiac tissues, and favorable degradation rates in vitro. Degree of tissue coverage, degradation and consequent changes in polymer thermomechanical properties, and inflammatory response in preclinical animal models are unknown material attributes required for translating this material into cardiovascular devices. This study investigates changes in the polymer structure, tissue coverage, endothelialization, and inflammation of percutaneously implanted PGD patches (20 mm × 9 mm x 0.5 mm) into the branch pulmonary arteries of Yorkshire pigs for three months. After three months in vivo, 5/8 samples exhibited (100%) tissue coverage, 2/8 samples exhibited 85-95% tissue coverage, and 1/8 samples exhibited limited (<20%) tissue coverage with mild-moderate inflammation. PGD explants showed a (60-70%) volume loss and (25-30%) mass loss, and a reduction in polymer crosslinks. Lumenal and mural surfaces and the cross-section of the explant demonstrated evidence of degradation. This study validates PGD as an appropriate cardiovascular engineering material due to its propensity for rapid tissue coverage and uneventful inflammatory response in a preclinical animal model, establishing a precedent for consideration in cardiovascular repair applications.

Evaluation of Topology Optimization Using 3D Printing for Bioresorbable Fusion Cages: A Biomechanical Study in a Porcine Model.

STUDY DESIGN: Preclinical biomechanical study of topology optimization versus standard ring design for bioresorbable poly-ε-caprolactone (PCL) cervical spine fusion cages delivering bone morphogenetic protein-2 (BMP-2) using a porcine model. OBJECTIVE: The aim was to evaluate range of motion (ROM) and bone fusion, as a function of topology optimization and BMP-2 delivery method. SUMMARY OF BACKGROUND DATA: 3D printing technology enables fabrication of topology-optimized cages using bioresorbable materials, offering several advantages including customization, and lower stiffness. Delivery of BMP-2 using topology optimization may enhance the quality of fusion. METHODS: Twenty-two 6-month-old pigs underwent anterior cervical discectomy fusion at one level using 3D printed PCL cages. Experimental groups (N=6 each) included: Group 1: ring design with surface adsorbed BMP-2, Group 2: topology-optimized rectangular design with surface adsorbed BMP-2, and Group 3: ring design with BMP-2 delivery via collagen sponge. Additional specimens, two of each design, were implanted without BMP-2, as controls. Complete cervical segments were harvested six months postoperatively. Nanocomputed tomography was performed to assess complete bony bridging. Pure moment biomechanical testing was conducted in all three planes, separately. Continuous 3D motions were recorded and analyzed. RESULTS: Three subjects suffered early surgical complications and were not evaluated. Overall, ROM for experimental specimens, regardless of design or BMP-2 delivery method, was comparable, with no clinically significant differences among groups. Among experimental specimens at the level of the fusion, ROM was <1.0° in flexion and extension, indicative of fusion, based on clinically applied criteria for fusion of <2 to 4°. Despite the measured biomechanical stability, using computed tomography evaluation, complete bony bridging was observed in 40% of the specimens in Group 1, 50% of Group 2, 100% of Group 3, and none of the control specimens. CONCLUSION: A topology-optimized PCL cage with BMP-2 is capable of resulting in an intervertebral fusion, similar to a conventional ring-based design of the same bioresorbable material.

Generative design approach to combine architected Voronoi foams with porous collagen scaffolds to create a tunable composite biomaterial.

Regenerative biomaterials for musculoskeletal defects must address multi-scale mechanical challenges. We are developing biomaterials for craniomaxillofacial bone defects that are often large and irregularly shaped. These require close conformal contact between implant and defect margins to aid healing. While we have identified a mineralized collagen scaffold that promotes mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo, its mechanical performance is insufficient for surgical translation. We report a generative design approach to create scaffold-mesh composites by embedding a macro-scale polymeric Voronoi mesh into the mineralized collagen scaffold. The mechanics of architected foam reinforced composites are defined by a rigorous predictive moduli equation. We show biphasic composites localize strain during loading. Further, planar and 3D mesh-scaffold composites can be rapidly shaped to aid conformal fitting. Voronoi-based composites overcome traditional porosity-mechanics relationship limits while enabling rapid shaping of regenerative implants to conformally fit complex defects unique for individual patients.

Generative design approach to combine architected Voronoi foams with porous collagen scaffolds to create a tunable composite biomaterial.

Regenerative biomaterials for musculoskeletal defects must address multi-scale mechanical challenges. Repairing craniomaxillofacial bone defects, which are often large and irregularly shaped, requires close conformal contact between implant and defect margins to aid healing. While mineralized collagen scaffolds can promote mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo, their mechanical performance is insufficient for surgical translation. We report a generative design approach to create scaffold-mesh composites by embedding a macro-scale polymeric Voronoi mesh into the mineralized collagen scaffold. The mechanics of architected foam reinforced composites are defined by a rigorous predictive moduli equation. We show biphasic composites localize strain during loading. Further, planar and 3D mesh-scaffold composites can be rapidly shaped to aid conformal fitting. Voronoi-based composites overcome traditional porosity-mechanics relationship limits while enabling rapid shaping of regenerative implants to conformally fit complex defects unique for individual patients. STATEMENT OF SIGNIFICANCE: Biomaterial strategies for (craniomaxillofacial) bone regeneration are often limited by the size and complex geometry of the defects. Voronoi structures are open-cell foams with tunable mechanical properties which have primarily been used computationally. We describe generative design strategies to create Voronoi foams via 3D-printing then embed them into an osteogenic mineralized collagen scaffold to form a multi-scale composite biomaterial. Voronoi structures have predictable and tailorable moduli, permit stain localization to defined regions of the composite, and permit conformal fitting to effect margins to aid surgical practicality and improve host-biomaterial interactions. Multi-scale composites based on Voronoi foams represent an adaptable design approach to address significant challenges to large-scale bone repair.

In vitro fatigue behavior and in vivo osseointegration of the auxetic porous bone screw.

The incidence of screw loosening, migration, and pullout caused by the insufficient screw-bone fixation stability is relatively high in clinical practice. To solve this issue, the auxetic unit-based porous bone screw (AS) has been put forward in our previous work. Its favorable auxetic effect can improve the primary screw-bone fixation stability after implantation. However, porous structure affected the fatigue behavior and in vivo longevity of bone screw. In this study, in vitro fatigue behaviors and in vivo osseointegration performance of the re-entrant unit-based titanium auxetic bone screw were studied. The tensile-tensile fatigue behaviors of AS and nonauxetic bone screw (NS) with the same porosity (51%) were compared via fatigue experiments, fracture analysis, and numerical simulation. The in vivo osseointegration of AS and NS were compared via animal experiment and biomechanical analysis. Additionally, the effects of in vivo dynamic tensile loading on the osseointegration of AS and NS were investigated and analyzed. The fatigue strength of AS was approximately 43% lower while its osseointegration performance was better than NS. Under in vivo dynamic tensile loading, the osseointegration of AS and NS both improved significantly, with the maximum increase of approximately 15%. Preferrable osseointegration of AS might compensate for the shortage of fatigue resistance, ensuring its long-term stability in vivo. Adequate auxetic effect and long-term stability of the AS was supposed to provide enough screw-bone fixation stability to overcome the shortages of the solid bone screw, developing the success of surgery and showing significant clinical application prospects in orthopedic surgery. STATEMENT OF SIGNIFICANCE: This research investigated the high-cycle fatigue behavior of re-entrant unit-based auxetic bone screw under tensile-tensile cyclic loading and its osseointegration performance, which has not been focused on in existing studies. The fatigue strength of auxetic bone screw was lower while the osseointegration was better than non-auxetic bone screw, especially under in vivo tensile loading. Favorable osseointegration of auxetic bone screw might compensate for the shortage of fatigue resistance, ensuring its long-term stability and longevity in vivo. This suggested that with adequate auxetic effect and long-term stability, the auxetic bone screw had significant application prospects in orthopedic surgery. Findings of this study will provide a theoretical guidance for design optimization and clinical application of the auxetic bone screw.

External airway splint placement for severe pediatric tracheobronchomalacia.

OBJECTIVE: To present external airway splinting with bioabsorbable airway supportive devices (ASD) for severe, life-threatening cases of pediatric tracheomalacia (TM) or tracheobronchomalacia (TBM). METHODS: A retrospective cohort was performed for 5 pediatric patients with severe TM or TBM who underwent ASD placement. Devices were designed and 3D-printed from a bioabsorbable material, polycaprolactone (PCL). Pre-operative planning included 3-dimensional airway modeling of tracheal collapse and tracheal suture placement using nonlinear finite element (FE) methods. Pre-operative modeling revealed that triads along the ASD open edges and center were the most effective suture locations for optimizing airway patency. Pediatric cardiothoracic surgery and otolaryngology applied the ASDs by suspending the trachea to the ASD with synchronous bronchoscopy. Respiratory needs were trended for all cases. Data from pediatric patients with tracheostomy and diagnosis of TM or TBM, but without ASD, were included for discussion. RESULTS: Five patients (2 Females, 3 Males, ages 2-9 months at time of ASD) were included. Three patients were unable to wean from respiratory support after vascular ring division; all three weaned to room air post-ASD. Two patients received tracheostomies prior to ASD placement, but continued to experience apparent life-threatening events (ALTE) and required ventilation with supraphysiologic ventilator settings. One patient weaned respiratory support successfully after ASD placement. The last patient died post-ASD due to significant respiratory co-morbidity. CONCLUSION: ASD can significantly benefit patients with severe, unrelenting tracheomalacia or tracheobronchomalacia. Proper multidisciplinary case deliberation and selection are key to success with ASD. Pre-operative airway modeling allows proper suture placement to optimally address the underlying airway collapse.

Finite element analysis of esophageal atresia repair with biodegradable polymer sleeves.

Esophageal atresia, which occurs in 1 in every 4100 live births, is a potentially lethal congenital malformation resulting in discontinuity of the esophagus. Treatment requires approximating the disconnected esophageal segments and suturing the ends to restore continuity. Due to excessive anastomotic tension, leaks and strictures are prevalent in primary surgical repair of the esophagus especially in the subset of neonates presenting with long gap atresia (>3 cm between esophageal segments). Extracellular matrix derived scaffolds and biodegradable polymer scaffolds have been investigated in preclinical models for use in alleviating esophageal anastomotic tension with varying degrees of success. We have previously described the suitability of biodegradable shape memory materials for use in a number of soft tissue repair applications. Developing repair strategies addressing esophageal atresia requires a framework for approximating tension at the anastomosis. In this study, we describe a computational framework for approximating esophageal anastomotic tension to study the impact of primary and device supported repair. The esophagus was modeled as an idealized concentric cylinder comprised of mucosal and muscle layers described by nonlinear strain energy functions and a mixed fiber model with a Neo-Hookean base material (FEBIO studio). Sutures were modeled as nonlinear elastic springs carrying only tension, and shape memory polymers were modeled as nonlinear elastic materials using one term Ogden parameters. The impact of suture bite (length of suture from anastomosis), sleeve material properties, sleeve suture strategy, and gap length were evaluated with respect to anastomotic LaGrangian strain, displacement magnitude, and strain energy density. With increasing gap length, there was an increase in anastomotic strain, displacement magnitude and strain energy density. Increasing the suture bite length decreased strain at the anastomosis. Application of the sleeve reduced strain, displacement and strain energy to a greater extent in longer gap atresia. Increasing the number of sutures to apply the sleeve did not decrease the esophageal strain compared to sleeves with lesser number of sutures. Sleeve material testing revealed an interplay between the nonlinear mechanical properties of the selected materials and their contribution to reducing anastomotic tension. Taken together this study provides a unique framework for computational verification of design hypothesis broadly addressing clinical procedure optimization, material design, and device design for surgical repair of esophageal atresia.

Clinical grade manufacture of 3D printed patient specific biodegradable devices for pediatric airway support.

Implantable patient-specific devices are the next frontier of personalized medicine, positioned to improve the quality of care across multiple clinical disciplines. Translation of patient-specific devices requires time- and cost-effective processes to design, verify and validate in adherence to FDA guidance for medical device manufacture. In this study, we present a generalized strategy for selective laser sintering (SLS) of patient-specific medical devices following the prescribed guidance for additive manufacturing of medical devices issued by the FDA in 2018. We contextualize this process for manufacturing an Airway Support Device, a life-saving tracheal and bronchial implant restoring airway patency for pediatric patients diagnosed with tracheobronchomalacia and exhibiting partial or complete airway collapse. The process covers image-based modeling, design inputs, design verification, material inputs and verification, device verification, and device validation, including clinical results. We demonstrate how design and material assessment lead to verified Airway Support Devices that achieve desired airway patency and reduction in required Positive End-Expiratory Pressure (PEEP) after patient implantation. We propose this process as a template for general quality control of patient-specific, 3D printed implants.

Tissue-engineered vascularized patient-specific temporomandibular joint reconstruction in a Yucatan pig model.

PURPOSE: Current pediatric temporomandibular joint (TMJ) reconstruction options are limited. The aim of this project was to develop a proof-of-principle porcine model for a load-bearing, customized, 3D-printed and bone morphogenic protein 2 (BMP-2)-coated scaffold implanted in a pedicled (temporal) flap as a regenerative approach to pediatric TMJ mandibular condyle reconstruction. MATERIALS AND METHODS: Scaffolds were customized, 3D-printed based on porcine computed tomography, and coated with BMP-2. Two operations occurred: (1) implantation of the scaffold in temporalis muscle to establish vascularity and, (2) 6 weeks later, unilateral condylectomy and rotation of the vascularized scaffold (with preservation of superficial temporal artery) onto the defect. Six months later, pigs were sacrified. The experimental side (muscle-scaffold) and control side (unoperated condyle) were individually evaluated by clinical, mechanical, radiographic, and histologic methods. RESULTS: Scaffolds maintained physical properties similar in appearance to unoperated condyles. Vascularized scaffolds had new bone formation. Condyle height on the reconstructed side was 68% and 78% of the control side. Reconstructed condyle stiffness was between 20% and 45% of the control side. CONCLUSION: In our porcine model, customized 3D-printed TMJ scaffolds coated with BMP-2 and implanted in vascularized temporalis muscle have the ability to (1) reconstruct a TMJ, (2) maintain appropriate condylar height, and (3) generate new bone, without impacting functional outcomes.

Early preclinical evaluation of a novel, computer aided designed, 3D printed, bioresorbable posterior cricoid scaffold.

OBJECTIVES: The posterior cricoid split with rib graft is a procedure that elegantly corrects pediatric posterior glottic stenosis and subglottic stenosis. Currently, the procedure requires harvesting of rib cartilage which leaves room for optimization. With use of three dimensional printing technology, our objective was to design a device that would negate the need for costal cartilage harvesting in this procedure. METHODS: An optimized, novel polycaprolactone scaffold was designed using computer aided design software and three dimensional printing. A pilot proof of concept study was conducted with implantation of the device in three porcine animal subjects. Device was evaluated by post-procedural clinical course, endoscopic exams, post-mortem exam, and histological evaluation. RESULTS: A series of variably sized scaffolds were created. The scaffolds showed structural integrity and successfully expanded the cricoid cartilage in the porcine model study. Post-operative endoscopy and clinical exams demonstrated no signs of implant instability or failure. Gross and histologic exams showed successful mucosalization over the scaffold and cartilage ingrowth by six weeks. CONCLUSION: This porcine animal pilot study demonstrated early success of a computer-aided designed, 3D printed, bioresorbable PCL posterior graft scaffold. The scaffolds eliminate the need for costal cartilage harvesting and had excellent surgical usability. The scaffolds functioned as designed, offering proof of concept and grounds for further evaluation to expand on this small pilot study with larger animal studies and continued design refinement.