In-Hospital 3D Printed Scaphoid Prosthesis Using Medical-Grade Polyetheretherketone (PEEK) Biomaterial.

Recently, three-dimensional (3D) printing has become increasingly popular in the medical sector for the production of anatomical biomodels, surgical guides, and prosthetics. With the availability of low-cost desktop 3D printers and affordable materials, the in-house or point-of-care manufacturing of biomodels and Class II medical devices has gained considerable attention in personalized medicine. Another projected development in medical 3D printing for personalized treatment is the in-house production of patient-specific implants (PSIs) for partial and total bone replacements made of medical-grade material such as polyetheretherketone (PEEK). We present the first in-hospital 3D printed scaphoid prosthesis using medical-grade PEEK with fused filament fabrication (FFF) 3D printing technology.

A three-dimensional printed patient-specific scaphoid replacement: a cadaveric study.

We present our first cadaveric test results of a three-dimensional printed patient-specific scaphoid replacement with tendon suspension, which showed normal motion behaviour and preservation of a stable scapholunate interval during physiological range of motion.

Corrective Osteotomy for Symptomatic Clavicle Malunion Using Patient-specific Osteotomy and Reduction Guides.

Midshaft clavicular fractures are often treated nonoperatively with good reported clinical outcome in a majority of patients. However, malunion with shortening of the affected clavicle is not uncommon. Shortening of the clavicle has been shown to affect shoulder strength and kinematics with alteration of scapular position. Whereas the exact clinical impact of these factors is unknown, the deformity may lead to cosmetic and functional impairment as for example pain with weight-bearing on the shoulder girdle. Other reported complications of clavicular malunion include thoracic outlet syndrome, subclavicular vein thrombosis, and axillary plexus compression. Corrective osteotomy has therefore been recommended for symptomatic clavicular malunions, generally using plain x-rays for planning the necessary elongation. Particularly in malunited multifragmentary fractures it may be difficult to exactly determine the plane of osteotomy intraoperatively to restore the precise anatomic shape of the clavicle. We present a technique for corrective osteotomy using preoperative computer planning and 3-dimensional printed patient-specific intraoperative osteotomy and reduction guides based on the healthy contralateral clavicle.

A Simple 3-Dimensional Printed Aid for a Corrective Palmar Opening Wedge Osteotomy of the Distal Radius.

The reconstruction of malunited distal radius fractures is often challenging. Virtual planning techniques and guides for drilling and resection have been used for several years to achieve anatomic reconstruction. These guides have the advantage of leading to better operative results and faster surgery. Here, we describe a technique using a simple implant independent 3-dimensional printed drill guide and template to simplify the surgical reconstruction of a malunited distal radius fracture.

Selective laser melted titanium implants: a new technique for the reconstruction of extensive zygomatic complex defects.

The restoration of extensive zygomatic complex defects is a surgical challenge owing to the difficulty of accurately restoring the normal anatomy, symmetry, proper facial projection and facial width. In the present study, an extensive post-traumatic zygomatic bone defect was reconstructed using a custom-made implant that was made with a selective laser melting (SLM) technique. The computer-designed implant had the proper geometry and fit perfectly into the defect without requiring any intraoperative adjustments. A one-year follow-up revealed a stable outcome with no complications.

Novel microcalorimetric assay for antibacterial activity of implant coatings: The cases of silver-doped hydroxyapatite and calcium hydroxide.

Biomaterials with antimicrobial properties are now commonly used in different clinical specialties including orthopedics, endodontic, and traumatology. As a result, assessing the antimicrobial effect of coatings applied on implants is of critical importance. In this study, we demonstrate that isothermal microcalorimetry (IMC) can be used for monitoring bacterial growth and biofilm formation at the surface of such coatings and for determining their antimicrobial effects. The antibacterial effects of silver doped hydroxyapatite (HA) and calcium hydroxide coatings on Staphylococcus epidermidis were determined with a minimal workload. Using the Gompertz growth model we determined biofilm growth rates close to those values reported in the literature. Furthermore, we were able to estimate the reduction in the bacterial inocula originally applied at the surface of the coatings. Therefore, in addition to monitoring the antimicrobial effect of silver doped HA and calcium hydroxide coatings, we also demonstrate that IMC might be a valuable tool for assessing such antimicrobial properties of implant coatings at a minimal workload.

Rapid prototyped porous nickel-titanium scaffolds as bone substitutes.

While calcium phosphate-based ceramics are currently the most widely used materials in bone repair, they generally lack tensile strength for initial load bearing. Bulk titanium is the gold standard of metallic implant materials, but does not match the mechanical properties of the surrounding bone, potentially leading to problems of fixation and bone resorption. As an alternative, nickel-titanium alloys possess a unique combination of mechanical properties including a relatively low elastic modulus, pseudoelasticity, and high damping capacity, matching the properties of bone better than any other metallic material. With the ultimate goal of fabricating porous implants for spinal, orthopedic and dental applications, nickel-titanium substrates were fabricated by means of selective laser melting. The response of human mesenchymal stromal cells to the nickel-titanium substrates was compared to mesenchymal stromal cells cultured on clinically used titanium. Selective laser melted titanium as well as surface-treated nickel-titanium and titanium served as controls. Mesenchymal stromal cells had similar proliferation rates when cultured on selective laser melted nickel-titanium, clinically used titanium, or controls. Osteogenic differentiation was similar for mesenchymal stromal cells cultured on the selected materials, as indicated by similar gene expression levels of bone sialoprotein and osteocalcin. Mesenchymal stromal cells seeded and cultured on porous three-dimensional selective laser melted nickel-titanium scaffolds homogeneously colonized the scaffold, and following osteogenic induction, filled the scaffold's pore volume with extracellular matrix. The combination of bone-related mechanical properties of selective laser melted nickel-titanium with its cytocompatibility and support of osteogenic differentiation of mesenchymal stromal cells highlights its potential as a superior bone substitute as compared to clinically used titanium.

Laser scanning evaluation of atrophy after autologous free muscle transfer.

Denervated muscle tissue undergoes morphologic changes that result in atrophy. The amount of muscle atrophy after denervation following free muscle transfer has not been measured so far. Therefore, the amount of muscle atrophy in human free muscle transfer for lower extremity reconstruction was measured in a series of 10 patients. Three-dimensional laser surface scanning was used to measure flap volume changes 2 weeks as well as 6 and 12 months after the operation. None of the muscles transferred was re-innervated.All muscles healed uneventfully without signs of compromised perfusion resulting in partial flap loss. The muscle volume decreased to 30 ± 4% and 19 ± 4% 6 and 12 months, respectively, after the operation, ie, the volume decreased by approximately 80% within a 12-month period.Denervated free muscle flap tissue undergoes massive atrophy of approximately 80%, mostly within the first 6 months.

Bone regeneration by the osteoconductivity of porous titanium implants manufactured by selective laser melting: a histological and micro computed tomography study in the rabbit.

The treatment of large bone defects still poses a major challenge in orthopaedic and cranio-maxillofacial surgery. One possible solution could be the development of personalized porous titanium-based implants that are designed to meet all mechanical needs with a minimum amount of titanium and maximum osteopromotive properties so that it could be combined with growth factor-loaded hydrogels or cell constructs to realize advanced bone tissue engineering strategies. Such implants could prove useful for mandibular reconstruction, spinal fusion, the treatment of extended long bone defects, or to fill in gaps created on autograft harvesting. The aim of this study was to determine the mechanical properties and potential of bone formation of light weight implants generated by selective laser melting (SLM). We mainly focused on osteoconduction, as this is a key feature in bone healing and could serve as a back-up for osteoinduction and cell transplantation strategies. To that end, defined implants were produced by SLM, and their surfaces were left untreated, sandblasted, or sandblasted/acid etched. In vivo bone formation with the different implants was tested throughout calvarial defects in rabbits and compared with untreated defects. Analysis by micro computed tomography (µCT) and histomorphometry revealed that all generatively produced porous Ti structures were well osseointegrated into the surrounding bone. The histomorphometric analysis revealed that bone formation was significantly increased in all implant-treated groups compared with untreated defects and significantly increased in sand blasted implants compared with untreated ones. Bone bridging was significantly increased in sand blasted acid-etched scaffolds. Therefore, scaffolds manufactured by SLM should be surface treated. Bone augmentation beyond the original bone margins was only seen in implant-treated defects, indicating an osteoconductive potential of the implants that could be utilized clinically for bone augmentation purposes. Therefore, designed porous, lightweight structures have potential for bone regeneration and augmentation purposes, especially when complex and patient-specific geometries are essential.

Cranioplasty with custom-made implants: analyzing the cases of 10 patients.

PURPOSE: The aim of this study was to assess quantitatively whether a symmetric reconstruction of the calvaria could be achieved using 3-dimensional (3D) custom-made implants and to examine any complications caused by the cranioplasty. PATIENTS AND METHODS: Custom-made cranial implants were produced using data obtained from computed tomographic scanning of the defect using computer-aided design and rapid prototyping techniques. Polymethylmethacrylate was used as the reconstruction material and the implant was cast from a silicone rubber mold. These implants were used in 10 patients (9 men and 1 woman) who previously received a craniectomy. The symmetry gained after cranioplasty was quantified by volumetric analysis using 3D reconstructed postoperative computed tomographic imaging. Any complications after cranioplasty also were recorded. RESULTS: The average follow-up was 42.5 months (range, 7 to 85 mo). The esthetic appearance of all patients was much improved. When the volume of the reconstructed right calvaria was compared with the left calvaria, the difference was not statistically significant (P > .05). There were 2 cases of complications. One exhibited a transient seroma collection. Another had a wrinkle formation in the forehead. No infectious episodes or signs of plate rejection were encountered. CONCLUSIONS: The custom-made implants for cranioplasty showed a significant improvement in morphology. The implants may be very useful for repairing large and complex-shaped cranial defects. The technique may be useful for the bone reconstruction of other sites.

Laryngeal electromyography: electrode guidance based on 3-dimensional magnetic resonance tomography images of the larynx.

OBJECTIVES/HYPOTHESIS: Laryngeal electromyography (LEMG) is an important tool for the assessment of laryngeal nerve and muscle functioning. The purpose of the study was to determine electrode insertion angle and insertion depth for the various laryngeal muscles. METHODS: Twenty-three cadaver larynges were examined with magnetic resonance tomography (MRT) and Materialize Interactive Medical Image Control System (Leuven, Belgium) 3-dimensional (3D) imaging software. Geometrical analysis was used to calculate the electrode insertion angles. RESULTS: All laryngeal muscles could be identified and 3D visualized on MRT scans. Although the insertion angles were the same in male and female larynges, the insertion depth was significantly larger in male than in female larynges (P<0.05). Of particular clinical importance is the fact that the electrode has to be directed lateral and upward for the thyroarytenoid muscle but lateral and downward for the lateral cricoarytenoid muscle (insertion point=midline lower border of the thyroid). CONCLUSIONS: This is the first study that analyzes electrode insertion angles and insertion depths for each laryngeal muscle using 3D imaging. We hope that the information gained from this study will help clinicians performing LEMG to localize the individual laryngeal muscles.

Mechanical implications of pneumatic neck vertebrae in sauropod dinosaurs.

The pre-sacral vertebrae of most sauropod dinosaurs were surrounded by interconnected, air-filled diverticula, penetrating into the bones and creating an intricate internal cavity system within the vertebrae. Computational finite-element models of two sauropod cervical vertebrae now demonstrate the mechanical reason for vertebral pneumaticity. The analyses show that the structure of the cervical vertebrae leads to an even distribution of all occurring stress fields along the vertebrae, concentrated mainly on their external surface and the vertebral laminae. The regions between vertebral laminae and the interior part of the vertebral body including thin bony struts and septa are mostly unloaded and pneumatic structures are positioned in these regions of minimal stress. The morphology of sauropod cervical vertebrae was influenced by strongly segmented axial neck muscles, which require only small attachment areas on each vertebra, and pneumatic epithelia that are able to resorb bone that is not mechanically loaded. The interaction of these soft tissues with the bony tissue of the vertebrae produced lightweight, air-filled vertebrae in which most stresses were borne by the external cortical bone. Cervical pneumaticity was therefore an important prerequisite for neck enlargement in sauropods. Thus, we expect that vertebral pneumaticity in other parts of the body to have a similar role in enabling gigantism.

Does abdominoplasty with liposuction of the love handles yield a shorter scar? An analysis with abdominal 3D laser scanning.

The aim of this study was to evaluate the combination of abdominoplasty with liposuction of both flanks with regards to length of scar, complications, and patient's satisfaction. A retrospective analysis of 35 patients who underwent esthetic abdominoplasty at our institution between 2002 and 2004 was performed. Thirteen patients underwent abdominoplasty with liposuction of both flanks, 22 patients underwent conventional abdominoplasty. Liposuction of the flanks did not increase the rate of complications of the abdominoplasty procedures. We found a tendency toward shorter scars in patients who underwent abdominoplasty combined with liposuction of the flanks. Implementation of 3-dimensional laser surface scanning to objectify the postoperative outcomes, documented a comparable degree of flatness of the achieved body contouring in both procedures. 3-dimensional laser surface scanning can be a valuable tool to objectify assessment of postoperative results.

Novel CCR5 monoclonal antibodies with potent and broad-spectrum anti-HIV activities.

To identify monoclonal antibodies (mAbs) with high potency and novel recognition sites, more than 25,000 of mouse hybridomas were screened and 4 novel anti-human CCR5 mAbs ROAb12, ROAb13, ROAb14, and ROAb18 showing potent activity in cell-cell fusion (CCF) assay were identified. These mAbs demonstrated potent antiviral activities in both single-cycle HIV infection (IC(50) range: 0.16-4.3 microg/ml) and PBMC viral replication (IC(50) range: 0.02-0.04 microg/ml) assays. These potent antiviral effects were donor-independent. All 4 mAbs were also highly potent in the PhenoSense assay against 29 HIV isolates covering clade A through G. In all antiviral assays, these mAbs showed potency superior to the previously reported mAb 2D7 in side-by-side comparison studies. All 4 mAbs were also fully active against viruses resistant to HIV fusion inhibitor enfuvirtide and CCR5 antagonist maraviroc. Although ROAb12, ROAb14, and ROAb18 inhibited RANTES, MIP1alpha and MIP1beta binding and cell activation, the other novel mAb ROAb13 was inactive in inhibiting cell activation by these three ligands. Furthermore, highly synergistic antiviral effects were found between mAb ROAb13 and 2D7 or ROAb12. In addition, none of these mAbs showed agonist activity or caused internalization of the CCR5 receptor.

Laser surface scanning analysis in reconstructive rhytidectomy.

The implementation of laser surface scanning to assess facial symmetry after unilateral face-lift procedures used to reconstruct defects after skin tumor resection is presented. Six patients who had undergone defect reconstruction with a flap raised from the subcutaneous plane were included in the study. Immediate postoperative photographic evaluation confirmed facial asymmetry because of unilateral skin tension. After a minimum follow-up period of 1 year, photographic and laser surface scanning analysis showed restored facial symmetry. In conclusion, laser surface scanning is a promising technology for objectifying results obtained and could be implemented for evaluation of the immediate and long-term effects from rhytidectomy procedures. Subcutaneous flaps without duplication or resection of the superficial musculoaponeurotic system are ideal for unilateral procedures because facial symmetry is restored after 1 year.

Rapid vessel prototyping: vascular modeling using 3t magnetic resonance angiography and rapid prototyping technology.

OBJECT: Conversion of thoracic aortic vasculature as measured by Magnetic Resonance Imaging into a real physical replica. MATERIALS AND METHODS: Several procedural steps including data acquisition with contrast enhanced MR Angiography at 3T, data visualization and 3D computer model generation, as well as rapid prototyping were used to construct an in-vitro model of the vessel geometry. RESULTS: A rapid vessel prototyping process was implemented and used to convert complex vascular geometry of the entire thoracic aorta and major branching arteries into a real physical replica with large anatomical coverage and high spatial resolution. CONCLUSION: Rapid vessel prototyping permits the creation of a concrete solid replica of a patient's vascular anatomy.

Structure-based optimization of novel azepane derivatives as PKB inhibitors.

Novel azepane derivatives were prepared and evaluated for protein kinase B (PKB-alpha) and protein kinase A (PKA) inhibition. The original (-)-balanol-derived lead structure (4R)-4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzoic acid (3R)-3-[(pyridine-4-carbonyl)amino]-azepan-4-yl ester (1) (IC(50) (PKB-alpha) = 5 nM) which contains an ester moiety was found to be plasma unstable and therefore unsuitable as a drug. Based upon molecular modeling studies using the crystal structure of the complex between PKA and 1, the five compounds N-[(3R,4R)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzoylamino]-azepan-3-yl]-isonicotinamide (4), (3R,4R)-N-[4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzyloxy]-azepan-3-yl]-isonicotinamide (5), N-[(3R,4S)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-phenylamino]-methyl]-azepan-3-yl)-isonicotinamide (6), N-[(3R,4R)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzylamino]-azepan-3-yl]-isonicotinamide (7), and N-[(3R,4S)-4-(4-[trans-2-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-phenyl]-vinyl]-azepan-3-yl)-isonicotinamide (8) with linkers isosteric to the ester were designed, synthesized, and tested for in vitro inhibitory activity against PKA and PKB-alpha and for plasma stability in mouse plasma.(1) Compound 4 was found to be plasma stable and highly active (IC(50) (PKB-alpha) = 4 nM). Cocrystals with PKA were obtained for 4, 5, and 8 and analyzed for binding interactions and conformational changes in the ligands and protein in order to rationalize the different activities of the molecules.