Patient-specific implants made of 3D printed bioresorbable polymers at the point-of-care: material, technology, and scope of surgical application.

BACKGROUND: Bioresorbable patient-specific additive-manufactured bone grafts, meshes, and plates are emerging as a promising alternative that can overcome the challenges associated with conventional off-the-shelf implants. The fabrication of patient-specific implants (PSIs) directly at the point-of-care (POC), such as hospitals, clinics, and surgical centers, allows for more flexible, faster, and more efficient processes, reducing the need for outsourcing to external manufacturers. We want to emphasize the potential advantages of producing bioresorbable polymer implants for cranio-maxillofacial surgery at the POC by highlighting its surgical applications, benefits, and limitations. METHODS: This study describes the workflow of designing and fabricating degradable polymeric PSIs using three-dimensional (3D) printing technology. The cortical bone was segmented from the patient's computed tomography data using Materialise Mimics software, and the PSIs were designed created using Geomagic Freeform and nTopology software. The implants were finally printed via Arburg Plastic Freeforming (APF) of medical-grade poly (L-lactide-co-D, L-lactide) with 30% ß-tricalcium phosphate and evaluated for fit. RESULTS: 3D printed implants using APF technology showed surfaces with highly uniform and well-connected droplets with minimal gap formation between the printed paths. For the plates and meshes, a wall thickness down to 0.8 mm could be achieved. In this study, we successfully printed plates for osteosynthesis, implants for orbital floor fractures, meshes for alveolar bone regeneration, and bone scaffolds with interconnected channels. CONCLUSIONS: This study shows the feasibility of using 3D printing to create degradable polymeric PSIs seamlessly integrated into virtual surgical planning workflows. Implementing POC 3D printing of biodegradable PSI can potentially improve therapeutic outcomes, but regulatory compliance must be addressed.

Geometric Cuts by an Autonomous Laser Osteotome Increase Stability in Mandibular Reconstruction With Free Fibula Grafts: A Cadaver Study.

BACKGROUND: Nonunion and plate exposure represent a major complication after mandibular reconstruction with free fibula flaps. These drawbacks may be resolved by geometric osteotomies increasing intersegmental bone contact area and stability. PURPOSE: The aim of this study was to compare intersegmental bone contact and stability of geometric osteotomies to straight osteotomies in mandibular reconstructions with free fibula grafts performed by robot-guided erbium-doped yttrium aluminum garnet laser osteotomy. STUDY DESIGN, SETTING, SAMPLE: This cadaveric in-vitro study was performed on fresh frozen human skull and fibula specimens. Computed tomography (CT) scans of all specimens were performed for virtual planning of mandibular resections and three-segment fibula reconstructions. The virtual planning was implemented in a Cold Ablation Robot-guided Laser Osteotome. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: For predictor variables, straight and geometric puzzle-shaped osteotomies were designed at resection of the mandible and corresponding fibula reconstruction. MAIN OUTCOME VARIABLES: The primary outcome variable was the stability of the reconstructed mandible investigated by shearing tests. Moreover, secondary outcome variables were the duration of the laser osteotomies, the contact surface area, and the accuracy of the reconstruction, both evaluated on postsurgical CT scans. COVARIATES: Covariables were not applicable. ANALYSES: Data were reported as mean values (± standard deviation) and were statistically analyzed using an independent-sample t-test at a significance level of α = 0.05. Root mean square deviation was tested for accuracy. RESULTS: Eight skulls and 16 fibula specimens were used for the study. One hundred twelve successful laser osteotomies (96 straight and 16 geometrical) could be performed. Geometric osteotomies increased stability (110.2 ± 36.2 N vs 37.9 ± 20.1 N, P < .001) compared to straight osteotomies. Geometric osteotomy of the fibula took longer than straight osteotomies (10.9 ± 5.1 min vs 5.9 ± 2.2 min, P = .028) but could provide larger contact surface (431.2 ± 148.5 mm2 vs 226.1 ± 50.8 mm2, P = .04). Heat map analysis revealed a mean deviation between preoperational planning and postreconstructive CT scan of -0.8 ± 2.4 mm and a root mean square deviation of 2.51 mm. CONCLUSION AND RELEVANCE: Mandibular resection and reconstruction by fibula grafts can be accurately performed by a Cold Ablation Robot-guided Laser Osteotome without need for cutting guides. Osteotomy planning with geometric cuts offers higher stability and an increased bone contact area, which may enhance healing of the reconstructed mandible.

3D-printed LEGO®-inspired titanium scaffolds for patient-specific regenerative medicine.

Despite the recent advances in 3D-printing, it is often difficult to fabricate implants that optimally fit a defect size or shape. There are some approaches to resolve this issue, such as patient-specific implant/scaffold designs based on CT images of the patients, however, this process is labor-intensive and costly. Especially in developing countries, affordable treatment options are required, while still not excluding these patient groups from potential material and manufacturing advances. Here, a selective laser melting (SLM) 3D-printing strategy was used to fabricate a hierarchical, LEGO®-inspired Assemblable Titanium Scaffold (ATS) system, which can be manually assembled in any shape or size with ease. A surgeon can quickly create a scaffold that would fit to the defect right before the implantation during the surgery. Additionally, the direct inclusion of micro- and macroporous structures via 3D-printing, as well as a double acid-etched surface treatment (ST) in the ATS, ensure biocompatibility, sufficient nutrient flow, cell migration and enhanced osteogenesis. Three different structures were designed (non-porous:NP, semi-porous:SP, ultra-porous:UP), 3D-printed with the SLM technique and then surface treated for the ST groups. After analyzing characteristics of the ATS such as printing quality, surface roughness and interconnected porosity, mechanical testing and finite element analysis (FEA) demonstrated that individual and stacked ATS have sufficient mechanical properties to withstand loading in a physiological system. All ATS showed high cell viability, and the SP and UP groups demonstrated enhanced cell proliferation rates compared to the NP group. Furthermore, we also verified that cells were well-attached and spread on the porous structures and successful cell migration between the ATS units was seen in the case of assemblies. The UP and SP groups exhibited higher calcium deposition and RT-qPCR proved higher osteogenic gene expression compared to NP group. Finally, we demonstrate a number of possible medical applications that reveal the potential of the ATS through assembly.

Three anchor concepts for rotator cuff repair in standardized physiological and osteoporotic bone: a biomechanical study.

BACKGROUND: Previous biomechanical studies used single-pull destructive tests in line with the anchor and are limited by a great variability of bone density of cadaver samples. To overcome these limitations, a more physiological test setting was provided using titanium, bioresorbable, and all-suture anchors. METHODS: In this controlled laboratory study, 3 anchor constructs were divided into 2 groups: physiological and osteoporotic. Sixty standardized artificial bone specimens (=10 for each anchor in each group) were used for biomechanical testing. The anchors were inserted at a 45° angle as during surgery. Cyclic loading for 1000 cycles followed by ultimate load-to-failure (ULTF) testing was performed. Elongation, ultimate load at failure, and the mode of failure were noted. RESULTS: In the physiological group, the ULTF for the all-suture anchor (mean [standard deviation], 632.9 [96.8 N]) was found to be significantly higher than for the other anchors (titanium, 497.1 [50.5] N, and bioresorbable, 322.4 [3.1 N], P < .0001). The titanium anchor showed a significantly higher ULTF than the bioresorbable anchor (P < .0001). In the osteoporotic group, the all-suture anchor again showed a higher ULTF compared to the bioresorbable anchor (500.9 [50.6] N vs. 315.1 [11.3] N, P < .0001). In the osteoporotic group, cyclic loading revealed a higher elongation after 1000 loading cycles for the bioresorbable (0.40 [0.12] mm) compared to the titanium (0.22 [0.11] mm; P = .01) as well as the all-suture anchor (0.19 [0.15] mm, P = .003). CONCLUSION: Regarding ULTF, the all-suture anchor outperformed the other anchors in physiological bone, but in osteoporotic bone, significance was reached only compared to the bioresorbable anchor. Although cyclic loading revealed significant differences, these might not be clinically relevant.

The new LassoLoop360° technique for biomechanically superior tissue grip.

PURPOSE: Suprapectoral tenodesis is a frequently used technique for treating pathologies of the long head of the biceps brachii (LHBB) tendon. However, so far, no Gold Standard treatment exist. Hence, the arthroscopic LassoLoop360 (LL360) technique is introduced aiming to provide secure fixation and improved biomechanical properties. It was hypothesized, that the LL360 technique would show superior biomechanical response to cyclic loading and ultimate load-to-failure testing compared to the commonly used simple Lasso Loop (SLL). METHODS: Twenty-two porcine superficial flexor digitorum tendons were prepared using a No. 2 suture according to either the SLL or the LL360 technique. Displacement after cyclic loading (1.000 cycles) between 5 and 30 N, ultimate load-to-failure (ULTF), mode of failure as well as the construct stiffness were tested. RESULTS: Significantly less displacement was found in the LL360 group (SLL 2.25 ± 0.51 mm; LL360 1.67 ± 0.37 mm; p = 0.01). Ultimate Load to Failure was significantly higher in the LL360 (168.6 ± 29.6 N) as compared to the SLL (124.1 ± 25.8 N, p = 0.02). The LL360 also revealed a significant higher stiffness compared to the SLL (SLL 13.1 ± 0.9 N/mm vs. LL360 19.1 ± 1.0 N/mm, p < 0.001). The most common mode of failure was the suture cutting through the tendon, with a significantly less suture cutting through for the LL360 compared with the SLL (p < 0.05). CONCLUSION: The LassoLoop360-technique offers superior biomechanical characteristics regarding the tendon-suture-interface compared to the SLL. In the initial healing phase, the suture-tendon-interface is the most vulnerable part of the tendon-suture-anchor construct, the aim of this new technique is to reduce this weakest part of the chain (Ponce et al., Am J Sports Med 39:188-194, 2011). This technique may therefore be beneficial for arthroscopic suprapectoral biceps tenodesis at the entrance of the bicipital groove.

A new model of implant-related osteomyelitis in the metaphysis of rat tibiae.

BACKGROUND: Animal models serve as an important tool to understand peri-implant infection. Most of the models use high bacterial loads (>10(4) colony forming units, CFU) to provide high infection rates. Therefore these animals evolve rather similarly, making comparison between groups and statistical analysis possible. On the other hand, to mimic clinical constellation of surgery-related infections the use of low amounts of bacteria would be more advantageous. METHODS: We developed a metaphyseal rat model of peri-implant bone infection with low amount of bacterial loads (10(2) and 10(3) CFU of Staphylococcus aureus) and investigated osseointegration of the implants coated with hydroxyapatite (HA) and low-dosed HA-silver (HA-Ag). Non-infected implants served as controls. After 6 weeks rats were sacrificed and implants evaluated for osseointegration and infection. RESULTS: Infection of implanted devices was reliably induced, independently whether 10(2) or 10(3) CFU of S. aureus were inoculated and HA or HA-Ag coated implants were used. No systemic infection was present in any of the animals at the time of sacrifice, and no animal developed acute infection requiring premature sacrifice. All CFU counts of the implant and the bone at sacrifice were significantly higher than the inoculated load (p < .05). All sterilely inserted implants showed excellent osseointegration and no infection. CONCLUSIONS: Our present study of a rat tibia model reliably induced osteomyelitis in the metaphysis with low-doses of bacteria. The addition of low-dosed Ag to the implant coating was not able to reduce the infection rates. The results demonstrate that it is possible to develop a model of implant-related osteomyelitis in rats with low amounts of bacteria to better mimic clinical constellations. No other promoters of infection besides insertion of the screw implant were used in this model.

Investigation of structural resorption behavior of biphasic bioceramics with help of gravimetry, µCT, SEM, and XRD.

Resorbable bone substitute materials are widely used for bone augmentation after tumor resection, parallel to implant placement, or in critical size bone defects. In this study, the structural dissolution of a biphasic calcium phosphate bone substitute material with a hydroxyapatite (HA)/tricalcium phosphate (ß-TCP) ratio of 60/40 was investigated by repeatedly placing porous blocks in EDTA solution at 37 °C. At several time points, the blocks were investigated by SEM, µCT, and gravimetry. It was found that always complete 2-3 µm sized grains were removed from the structure and that the ß-TCP is dissolved more rapidly. This selective dissolution of the ß-TCP grains was confirmed by XRD measurements. The blocks were eroded from the outside toward the center. The structure remained mechanically stable because the central part showed a delayed degradation and because the slower dissolving HA grains preserved the integrity of the structure.

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.

All-inside meniscal repair devices compared with their matched inside-out vertical mattress suture repair: introducing 10,000 and 100,000 loading cycles.

BACKGROUND: All-inside arthroscopic meniscal repairs are favored by most clinicians because of their lower complication rate and decreased morbidity compared with inside-out techniques. Until now, only 1000 cycles have been used for biomechanical testing. HYPOTHESIS: All-inside meniscal repairs will show inferior biomechanical response to cyclic loading (up to 100,000 cycles) and load-to-failure testing compared with inside-out suture controls. STUDY DESIGN: Controlled laboratory study. METHODS: Bucket-handle tears in 72 porcine menisci were repaired using the Omnispan and Fast-Fix 360 (all-inside devices) and Orthocord 2-0 and Ultrabraid 2-0 sutures (matched controls). Initial displacement, displacement after cyclic loading (100, 500, 1000, 2000, 5000, 10,000, and 100,000 cycles) between 5 and 20 N, ultimate load to failure, and mode of failure were recorded, as well as stiffness. RESULTS: Initial displacement and displacement after cyclic loading were not different between the groups. The Omnispan repair demonstrated the highest load-to-failure force (mean ± SD, 151.3 ± 21.5 N) and was significantly stronger than all the other constructs (Orthocord 2-0, 105.5 ± 20.4 N; Ultrabraid 2-0, 93.4 ± 22.5 N; Fast-Fix 360, 76.6 ± 14.2 N) (P < .0001 for all). The Orthocord vertical inside-out mattress repair was significantly stronger than the Fast-Fix 360 repair (P = .003). The Omnispan (30.8 ± 3.5 N/mm) showed significantly higher stiffness compared with the Ultrabraid 2-0 (22.9 ± 6.9 N/mm, P < .0001) and Fast-Fix 360 (23.7 ± 3.9 N/mm, P = .001). The predominant mode of failure was suture failure. CONCLUSION: All-inside meniscal devices show comparable biomechanical properties compared with inside-out suture repair in cyclic loading, even after 100,000 cycles. CLINICAL RELEVANCE: Eight to 10 weeks of rehabilitation might not pose a problem for all repairs in this worst-case scenario.

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.

Modulation of human osteoblasts by metal surface chemistry.

The use of metal implants in dental and orthopedic surgery is continuously expanding and highly successful. While today longevity and load-bearing capacity of the implants fulfill the expectations of the patients, acceleration of osseointegration would be of particular benefit to shorten the period of convalescence. To further clarify the options to accelerate the kinetics of osseointegration, within this study, the osteogenic properties of structurally identical surfaces with different metal coatings were investigated. To assess the development and function of primary human osteoblasts on metal surfaces, cell viability, differentiation, and gene expression were determined. Titanium surfaces were used as positive, and surfaces coated with gold were used as negative controls. Little differences in the cellular parameters tested for were found when the cells were grown on titanium discs sputter coated with titanium, zirconium, niobium, tantalum, gold, and chromium. Cell number, activity of cell layer-associated alkaline phosphatase (ALP), and levels of transcripts encoding COL1A1 and BGLAP did not vary significantly in dependence of the surface chemistry. Treatment of the cell cultures with 1,25(OH)2 D3 /Dex, however, significantly increased ALP activity and BGLAP messenger RNA levels. The data demonstrate that the metal layer coated onto the titanium discs exerted little modulatory effects on cell behavior. It is suggested that the microenvironment regulated by the peri-implant tissues is more effective in regulating the tissue response than is the material of the implant itself.