Development of End-to-End Artificial Intelligence Models for Surgical Planning in Transforaminal Lumbar Interbody Fusion.

Transforaminal lumbar interbody fusion (TLIF) is a commonly used technique for treating lumbar degenerative diseases. In this study, we developed a fully computer-supported pipeline to predict both the cage height and the degree of lumbar lordosis subtraction from the pelvic incidence (PI-LL) after TLIF surgery, utilizing preoperative X-ray images. The automated pipeline comprised two primary stages. First, the pretrained BiLuNet deep learning model was employed to extract essential features from X-ray images. Subsequently, five machine learning algorithms were trained using a five-fold cross-validation technique on a dataset of 311 patients to identify the optimal models to predict interbody cage height and postoperative PI-LL. LASSO regression and support vector regression demonstrated superior performance in predicting interbody cage height and postoperative PI-LL, respectively. For cage height prediction, the root mean square error (RMSE) was calculated as 1.01, and the model achieved the highest accuracy at a height of 12 mm, with exact prediction achieved in 54.43% (43/79) of cases. In most of the remaining cases, the prediction error of the model was within 1 mm. Additionally, the model demonstrated satisfactory performance in predicting PI-LL, with an RMSE of 5.19 and an accuracy of 0.81 for PI-LL stratification. In conclusion, our results indicate that machine learning models can reliably predict interbody cage height and postoperative PI-LL.

Effect of Porosity and Heat Treatment on Mechanical Properties of Additive Manufactured CoCrMo Alloys.

To minimize the stress shielding effect of metallic biomaterials in mimicking bone, the body-centered cubic (bcc) unit cell-based porous CoCrMo alloys with different, designed volume porosities of 20, 40, 60, and 80% were produced via a selective laser melting (SLM) process. A heat treatment process consisting of solution annealing and aging was applied to increase the volume fraction of an ε-hexagonal close-packed (hcp) structure for better mechanical response and stability. In the present study, we investigated the impact of different, designed volume porosities on the compressive mechanical properties in as-built and heat-treated CoCrMo alloys. The elastic modulus and yield strength in both conditions were dramatically decreased with increasing designed volume porosity. The elastic modulus and yield strength of the CoCrMo alloys with a designed volume porosity of 80% exhibited the closest match to those of bone tissue. Different strengthening mechanisms were quantified to determine their contributing roles to the measured yield strength in both conditions. The experimental results of the relative elastic modulus and yield strength were compared to the analytical and simulation modeling analyses. The Gibson-Ashby theoretical model was established to predict the deformation behaviors of the lattice CoCrMo structures.

Biocompatibility and Biological Performance of Additive-Manufactured Bioabsorbable Iron-Based Porous Interference Screws in a Rabbit Model: A 1-Year Observational Study.

This study evaluated the mid-term (12-month) biomechanical, biocompatibility, and biological performance of additive-manufactured bioabsorbable iron-based interference screws (ISs). Two bioabsorbable iron IS types-manufactured using pure iron powder (iron_IS) and using pure iron powder with 0.2 wt% tricalcium phosphate (TCP_IS)-were compared with conventional metallic IS (control) using in vitro biocompatibility and degradation analyses and an in vivo animal study. The in vitro ultimate failure strength was significantly higher for iron_IS and TCP_IS than for control ISs at 3 months post-operatively; however, the difference between groups were nonsignificant thereafter. Moreover, at 3 months after implantation, iron_IS and TCP_IS increased bone volume fraction, bone surface area fraction, and percent intersection surface; the changes thereafter were nonsignificant. Iron_IS and TCP_IS demonstrated degradation over time with increased implant surface, decreased implant volume, and structure thickness; nevertheless, the analyses of visceral organs and biochemistry demonstrated normal results, except for time-dependent iron deposition in the spleen. Therefore, compared with conventional ISs, bioabsorbable iron-based ISs exhibit higher initial mechanical strength. Although iron-based ISs demonstrate high biocompatibility 12 months after implantation, their corrosive iron products may accumulate in the spleen. Because they demonstrate mechanical superiority along with considerable absorption capability after implantation, iron-based ISs may have potential applications in implantable medical-device development in the future.

Correction: Liu et al. 3D-Printed Double-Helical Biodegradable Iron Suture Anchor: A Rabbit Rotator Cuff Tear Model Materials 2022, 15, 2801.

In the original publication [...].

Detection of Lumbar Spondylolisthesis from X-ray Images Using Deep Learning Network.

Spondylolisthesis refers to the displacement of a vertebral body relative to the vertrabra below it, which can cause radicular symptoms, back pain or leg pain. It usually occurs in the lower lumbar spine, especially in women over the age of 60. The prevalence of spondylolisthesis is expected to rise as the global population ages, requiring prudent action to promptly identify it in clinical settings. The goal of this study was to develop a computer-aided diagnostic (CADx) algorithm, LumbarNet, and to evaluate the efficiency of this model in automatically detecting spondylolisthesis from lumbar X-ray images. Built upon U-Net, feature fusion module (FFM) and collaborating with (i) a P-grade, (ii) a piecewise slope detection (PSD) scheme, and (iii) a dynamic shift (DS), LumbarNet was able to analyze complex structural patterns on lumbar X-ray images, including true lateral, flexion, and extension lateral views. Our results showed that the model achieved a mean intersection over union (mIOU) value of 0.88 in vertebral region segmentation and an accuracy of 88.83% in vertebral slip detection. We conclude that LumbarNet outperformed U-Net, a commonly used method in medical image segmentation, and could serve as a reliable method to identify spondylolisthesis.

Mitigation of age-dependent accumulation of defective mitochondrial genomes.

Unknown processes promote the accumulation of mitochondrial DNA (mtDNA) mutations during aging. Accumulation of defective mitochondrial genomes is thought to promote the progression of heteroplasmic mitochondrial diseases and degenerative changes with natural aging. We used a heteroplasmic Drosophila model to test 1) whether purifying selection acts to limit the abundance of deleterious mutations during development and aging, 2) whether quality control pathways contribute to purifying selection, 3) whether activation of quality control can mitigate accumulation of deleterious mutations, and 4) whether improved quality control improves health span. We show that purifying selection operates during development and growth but is ineffective during aging. Genetic manipulations suggest that a quality control process known to enforce purifying selection during oogenesis also suppresses accumulation of a deleterious mutation during growth and development. Flies with nuclear genotypes that enhance purifying selection sustained higher genome quality, retained more vigorous climbing activity, and lost fewer dopaminergic neurons. A pharmacological agent thought to enhance quality control produced similar benefits. Importantly, similar pharmacological treatment of aged mice reversed age-associated accumulation of a deleterious mtDNA mutation. Our findings reveal dynamic maintenance of mitochondrial genome fitness and reduction in the effectiveness of purifying selection during life. Importantly, we describe interventions that mitigate and even reverse age-associated genome degeneration in flies and in mice. Furthermore, mitigation of genome degeneration improved well-being in a Drosophila model of heteroplasmic mitochondrial disease.

In Vitro and In Vivo Comparison of Bone Growth Characteristics in Additive-Manufactured Porous Titanium, Nonporous Titanium, and Porous Tantalum Interbody Cages.

Autogenous bone grafts are the gold standard for interbody fusion implant materials; however, they have several disadvantages. Tantalum (Ta) and titanium (Ti) are ideal materials for interbody cages because of their biocompatibility, particularly when they are incorporated into a three-dimensional (3D) porous structure. We conducted an in vitro investigation of the cell attachment and osteogenic markers of self-fabricated uniform porous Ti (20%, 40%, 60%, and 80%), nonporous Ti, and porous Ta cages (n = 6) in each group. Cell attachment, osteogenic markers, and alkaline phosphatase (ALP) were measured. An in vivo study was performed using a pig-posterior-instrumented anterior interbody fusion model to compare the porous Ti (60%), nonporous Ti, and porous Ta interbody cages in 12 pigs. Implant migration and subsidence, determined using plain radiographs, were recorded before surgery, immediately after surgery, and at 1, 3, and 6 months after surgery. Harvested implants were assessed for bone ingrowth and attachment. Relative to the 20% and 40% porous Ti cages, the 60% and 80% cages achieved superior cellular migration into cage pores. Among the cages, osteogenic marker and ALP activity levels were the highest in the 60% porous Ti cage, osteocalcin expression was the highest in the nonporous Ti cage, and the 60% porous Ti cage exhibited the lowest subsidence. In conclusion, the designed porous Ti cage is biocompatible and suitable for lumbar interbody fusion surgery and exhibits faster fusion with less subsidence compared with porous Ta and nonporous Ti cages.

3D-Printed Double-Helical Biodegradable Iron Suture Anchor: A Rabbit Rotator Cuff Tear Model.

Suture anchors are extensively used in rotator cuff tear surgery. With the advancement of three-dimensional printing technology, biodegradable metal has been developed for orthopedic applications. This study adopted three-dimensional-printed biodegradable Fe suture anchors with double-helical threads and commercialized non-vented screw-type Ti suture anchors with a tapered tip in the experimental and control groups, respectively. The in vitro study showed that the Fe and Ti suture anchors exhibited a similar ultimate failure load in 20-pound-per-cubic-foot polyurethane foam blocks and rabbit bone. In static immersion tests, the corrosion rate of Fe suture anchors was 0.049 ± 0.002 mm/year. The in vivo study was performed on New Zealand white rabbits and SAs were employed to reattach the ruptured supraspinatus tendon. The in vivo ultimate failure load of the Fe suture anchors was superior to that of the Ti suture anchors at 6 weeks. Micro-computed tomography showed that the bone volume fraction and bone surface density in the Fe suture anchors group 2 and 6 weeks after surgery were superior, and the histology confirmed that the increased bone volume around the anchor was attributable to mineralized osteocytes. The three-dimensional-printed Fe suture anchors outperformed the currently used Ti suture anchors.

Biocompatibility and Biological Performance Evaluation of Additive-Manufactured Bioabsorbable Iron-Based Porous Suture Anchor in a Rabbit Model.

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.

Tailoring grain sizes of the biodegradable iron-based alloys by pre-additive manufacturing microalloying.

We demonstrated the design of pre-additive manufacturing microalloying elements in tuning the microstructure of iron (Fe)-based alloys for their tunable mechanical properties. We tailored the microalloying stoichiometry of the feedstock to control the grain sizes of the metallic alloy systems. Two specific microalloying stoichiometries were reported, namely biodegradable iron powder with 99.5% purity (BDFe) and that with 98.5% (BDFe-Mo). Compared with the BDFe, the BDFe-Mo powder was found to have lower coefficient of thermal expansion (CTE) value and better oxidation resistance during consecutive heating and cooling cycles. The selective laser melting (SLM)-built BDFe-Mo exhibited high ultimate tensile strength (UTS) of 1200 MPa and fair elongation of 13.5%, while the SLM-built BDFe alloy revealed a much lower UTS of 495 MPa and a relatively better elongation of 17.5%, indicating the strength enhancement compared with the other biodegradable systems. Such an enhanced mechanical behavior in the BDFe-Mo was assigned to the dominant mechanism of ferrite grain refinement coupled with precipitate strengthening. Our findings suggest the tunability of outstanding strength-ductility combination by tailoring the pre-additive manufacturing microalloying elements with their proper concentrations.

Additive-manufactured Ti-6Al-4 V/Polyetheretherketone composite porous cage for Interbody fusion: bone growth and biocompatibility evaluation in a porcine model.

BACKGROUND: We developed a porous Ti alloy/PEEK composite interbody cage by utilizing the advantages of polyetheretherketone (PEEK) and titanium alloy (Ti alloy) in combination with additive manufacturing technology. METHODS: Porous Ti alloy/PEEK composite cages were manufactured using various controlled porosities. Anterior intervertebral lumbar fusion and posterior augmentation were performed at three vertebral levels on 20 female pigs. Each level was randomly implanted with one of the five cages that were tested: a commercialized pure PEEK cage, a Ti alloy/PEEK composite cage with nonporous Ti alloy endplates, and three composite cages with porosities of 40, 60, and 80%, respectively. Micro-computed tomography (CT), backscattered-electron SEM (BSE-SEM), and histological analyses were performed. RESULTS: Micro-CT and histological analyses revealed improved bone growth in high-porosity groups. Micro-CT and BSE-SEM demonstrated that structures with high porosities, especially 60 and 80%, facilitated more bone formation inside the implant but not outside the implant. Histological analysis also showed that bone formation was higher in Ti alloy groups than in the PEEK group. CONCLUSION: The composite cage presents the biological advantages of Ti alloy porous endplates and the mechanical and radiographic advantages of the PEEK central core, which makes it suitable for use as a single implant for intervertebral fusion.

Mitochondrial UQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy.

Parkinson's disease is a neurodegenerative disorder with a multifactorial aetiology. Nevertheless, the genetic predisposition in many families with multi-incidence disease remains unknown. This study aimed to identify novel genes that cause familial Parkinson's disease. Whole exome sequencing was performed in three affected members of the index family with a late-onset autosomal-dominant parkinsonism and polyneuropathy. We identified a novel heterozygous substitution c.941A>C (p.Tyr314Ser) in the mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene, which co-segregates with disease within the family. Additional analysis of 699 unrelated Parkinson's disease probands with autosomal-dominant Parkinson's disease and 1934 patients with sporadic Parkinson's disease revealed another two variants in UQCRC1 in the probands with familial Parkinson's disease, c.931A>C (p.Ile311Leu) and an allele with concomitant splicing mutation (c.70-1G>A) and a frameshift insertion (c.73_74insG, p.Ala25Glyfs*27). All substitutions were absent in 1077 controls and the Taiwan Biobank exome database from healthy participants (n = 1517 exomes). We then assayed the pathogenicity of the identified rare variants using CRISPR/Cas9-based knock-in human dopaminergic SH-SY5Y cell lines, Drosophila and mouse models. Mutant UQCRC1 expression leads to neurite degeneration and mitochondrial respiratory chain dysfunction in SH-SY5Y cells. UQCRC1 p.Tyr314Ser knock-in Drosophila and mouse models exhibit age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity and aberrant mitochondrial ultrastructures in nigral neurons. Furthermore, intraperitoneal injection of levodopa could significantly improve the motor dysfunction in UQCRC1 p.Tyr314Ser mutant knock-in mice. Taken together, our in vitro and in vivo studies support the functional pathogenicity of rare UQCRC1 variants in familial parkinsonism. Our findings expand an additional link of mitochondrial complex III dysfunction in Parkinson's disease.

Investigation of Bone Growth in Additive-Manufactured Pedicle Screw Implant by Using Ti-6Al-4V and Bioactive Glass Powder Composite.

In this study, we optimized the geometry and composition of additive-manufactured pedicle screws. Metal powders of titanium-aluminum-vanadium (Ti-6Al-4V) were mixed with reactive glass-ceramic biomaterials of bioactive glass (BG) powders. To optimize the geometry of pedicle screws, we applied a novel numerical approach to proposing the optimal shape of the healing chamber to promote biological healing. We examined the geometry and composition effects of pedicle screw implants on the interfacial autologous bone attachment and bone graft incorporation through in vivo studies. The addition of an optimal amount of BG to Ti-6Al-4V leads to a lower elastic modulus of the ceramic-metal composite material, effectively reducing the stress-shielding effects. Pedicle screw implants with optimal shape design and made of the composite material of Ti-6Al-4V doped with BG fabricated through additive manufacturing exhibit greater osseointegration and a more rapid bone volume fraction during the fracture healing process 120 days after implantation, per in vivo studies.

Novel design of additive manufactured hollow porous implants.

OBJECTIVE: Our aim is to examine the mechanical properties of two types of additive manufactured hollow porous dental implants and 6 and 12-week bone ingrowth after insertion in animals. A 3D numerical model is also developed to show detailed tissue differentiation and to provide design guidelines for implants. METHODS: The two porous and a commercial dental implant were studied by series of in vitro mechanical tests (three-point bending, torsional, screwing torque, and sawbone pull-out tests). They also evaluated by in vivo animal tests (micro-CT analysis) and ex vivo pull-out tests. Moreover, the mechano-regulation algorithm was implemented by the 3D finite element model to predict the history of tissue differentiation around the implants. RESULTS: The results showed that the two porous implants can significantly improve osseointegration after 12-week bone healing. This resulted in good fixation and stability of implants, giving very high maximum pull-out strength 413.1 N and 493.2 N, compared to 245.7 N for the commercial implant. Also, several features were accurately predicted by the mechano-regulation model, such as transversely connected bone formation, and bone resorption occurred in the middle of implants. SIGNIFICANCE: Systematic studies on dental implants with multiple approaches, including new design, mechanical tests, animal tests, and numerical modeling, were performed. Two hollow porous implants significantly improved bone ingrowth compared with commercial implants, while maintaining mechanical strength. Also, the numerical model was verified by animal tests. It improved the efficiency of design and reduce the demand for animal sacrifice.

Three-Dimensional Printed Porous Titanium Screw with Bioactive Surface Modification for Bone-Tendon Healing: A Rabbit Animal Model.

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.

3D laser-printed porous Ti6Al4V dental implants for compromised bone support.

BACKGROUND/PURPOSE: Alveolar bone loss following peri-implantitis remains a clinical challenge. We aimed to design a novel bioactive dental implant to accommodate the large bone defect caused by removal of previously failed implant. METHODS: Bio-ActiveITRI dental implant was manufactured with laser-sintered additive 3D printing technique. A 7.5 mm diameter × 7.0 mm depth osteotomy defect was created at the lateral aspect of distal femur of 20 New Zealand white rabbits to simulate the bony defect after removal of failed dental implant. One side of distal femurs was randomly selected for the commercially pure titanium NobelActive™ implant (control group) and the other side with Bio-ActiveITRI Ti6Al4V porous dental implant (ITRI group). Animals were sacrificed at 4, 8 and 12 weeks after the implants' insertion. The samples were processed for gross morphological analysis, radiographic examination, micro-CT evaluation, and mechanical testing. RESULTS: In histomorphometrical evaluation and micro-CT analysis, active new bone formation and good osseointegration within the ITRI implants were observed at the bone gap surrounding the dental implants. The biomechanical parameters in the Bio-ActiveITRI dental implants were significantly higher than those of the commercially control samples. For the Bio-ActiveITRI dental implants, the trabecular thickness decreased, while the trabecular separation and total porosity increased from the prescribed 1-month to 3-month time points; reflecting the natural remodeling of surrounding bony tissue in the Bio-ActiveITRI dental implants. CONCLUSION: The novel porous structured Bio-ActiveITRI dental implants may have a great potential for the prosthetic reconstruction where bone support is compromised after removal of a previously failed implant.

A potential peptide derived from cytokine receptors can bind proinflammatory cytokines as a therapeutic strategy for anti-inflammation.

Chronic inflammation is a pivotal event in the pathogenesis of cardiovascular diseases, including atherosclerosis, restenosis, and coronary artery disease. The efficacy of current treatment or preventive strategies for such inflammation is still inadequate. Thus, new anti-inflammatory strategies are needed. In this study, based on molecular docking and structural analysis, a potential peptide KCF18 with amphiphilic properties (positively charged and hydrophobic residues) derived from the receptors of proinflammatory cytokines was designed to inhibit cytokine-induced inflammatory response. Simulations suggested that KCF18 could bind to cytokines simultaneously, and electrostatic interactions were dominant. Surface plasmon resonance detection showed that KCF18 bound to both tumor necrosis factor-α (TNF-α) and interleukin-6, which is consistent with MM/PBSA binding free energy calculations. The cell experiments showed that KCF18 significantly reduced the binding of proinflammatory cytokines to their cognate receptors, suppressed TNF-α mRNA expression and monocyte binding and transmigration, and alleviated the infiltration of white blood cells in a peritonitis mouse model. The designed peptide KCF18 could remarkably diminish the risk of vascular inflammation by decreasing plasma cytokines release and by directly acting on the vascular endothelium. This study demonstrated that a combination of structure-based in silico design calculations, together with experimental measurements can be used to develop potential anti-inflammatory agents.

Augmentation of DMLS Biomimetic Dental Implants with Weight-Bearing Strut to Balance of Biologic and Mechanical Demands: From Bench to Animal.

A mismatch of elastic modulus values could result in undesirable bone resorption around the dental implant. The objective of this study was to optimize direct metal laser sintering (DMLS)-manufactured Ti6Al4V dental implants' design, minimize elastic mismatch, allow for maximal bone ingrowth, and improve long-term fixation of the implant. In this study, DMLS dental implants with different morphological characteristics were fabricated. Three-point bending, torsional, and stability tests were performed to compare the mechanical properties of different designs. Improvement of the weaker design was attempted by augmentation with a longitudinal 3D-printed strut. The osseointegrative properties were evaluated. The results showed that the increase in porosity decreased the mechanical properties, while augmentation with a longitudinal weight-bearing strut can improve mechanical strength. Maximal alkaline phosphatase gene expression of MG63 cells attained on 60% porosity Ti6Al4V discs. In vivo experiments showed good incorporation of bone into the porous scaffolds of the DMLS dental implant, resulting in a higher pull-out strength. In summary, we introduced a new design concept by augmenting the implant with a longitudinal weight-bearing strut to achieve the ideal combination of high strength and low elastic modulus; our results showed that there is a chance to reach the balance of both biologic and mechanical demands.

Improvement of bone-tendon fixation by porous titanium interference screw: A rabbit animal model.

The interference screw is a widely used fixation device in the anterior cruciate ligament (ACL) reconstruction surgeries. Despite the generally satisfactory results, problems of using interference screws were reported. By using additive manufacturing (AM) technology, we developed an innovative titanium alloy (Ti6 Al4 V) interference screw with rough surface and inter-connected porous structure designs to improve the bone-tendon fixation. An innovative Ti6 Al4 V interference screws were manufactured by AM technology. In vitro mechanical tests were performed to validate its mechanical properties. Twenty-seven New Zealand white rabbits were randomly divided into control and AM screw groups for biomechanical analyses and histological analysis at 4, 8, and 12 weeks postoperatively; while micro-CT analysis was performed at 12 weeks postoperatively. The biomechanical tests showed that the ultimate failure load in the AM interference screw group was significantly higher than that in the control group at all tested periods. These results were also compatible with the findings of micro-CT and histological analyses. In micro-CT analysis, the bone-screw gap was larger in the control group; while for the additive manufactured screw, the screw and bone growth was in close contact. In histological study, the bone-screw gaps were wider in the control group and were almost invisible in the AM screw group. The innovative AM interference screws with surface roughness and inter-connected porous architectures demonstrated better bone-tendon-implant integration, and resulted in stronger biomechanical characteristics when compared to traditional screws. These advantages can be transferred to future interference screw designs to improve their clinical performance. The AM interference screw could improve graft fixation and eventually result in better biomechanical performance of the bone-tendon-screw construct. The innovative AM interference screws can be transferred to future interference screw designs to improve the performance of implants. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2633-2640, 2018.

PINK1 Phosphorylates MIC60/Mitofilin to Control Structural Plasticity of Mitochondrial Crista Junctions.

Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in their regulation. Mitochondria increase crista junctions and numbers in selective subcellular areas, and this remodeling requires PINK1 to phosphorylate the inner mitochondrial membrane protein MIC60/mitofilin, which stabilizes MIC60 oligomerization. Expression of MIC60 restores crista structure and ATP levels of PINK1-null flies and remarkably rescues their behavioral defects and dopaminergic neurodegeneration. In an extension to human relevance, we discover that the PINK1-MIC60 pathway is conserved in human neurons, and expression of several MIC60 coding variants in the mitochondrial targeting sequence found in PD patients in Drosophila impairs crista junction formation and causes locomotion deficits. These findings highlight the importance of maintenance and plasticity of crista junctions to cellular homeostasis in vivo.