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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Are suspensory ligaments important for middle ear reconstruction?

As the resolution of 3D printing techniques improves, the possibility of individualized, 3-ossicle constructions adds a new dimension to middle ear prostheses. In order to optimize these designs, it is essential to understand how the ossicles and ligaments work together to transmit sound, and thus how ligaments should be replicated in a middle ear reconstruction. The middle ear ligaments are thought to play a significant role in maintaining the position of the ossicles and constraining axis of rotation. Paradoxically, investigations of the role of ligaments to date have shown very little impact on middle ear sound transmission. We explored the role of the two attachments in the gerbil middle ear analogous to human ligaments, the posterior incudal ligament and the anterior mallear process, severing both attachments and measuring change in hearing sensitivity. The impact of severing the attachments on the position of the ossicular chain was visualized using synchrotron microtomography imaging of the middle ear. In contrast to previous studies, a threshold change on the order of 20 dB across a wide range of frequencies was found when both ligaments were severed. Concomitantly, a shift in position of the ossicles was observed from the x-ray imaging and 3D renderings of the ossicular chain. These findings contrast with previous studies, demonstrating that these ligaments play a significant role in the transmission of sound through the middle ear. It appears that both mallear and incudal ligaments must be severed in order to impair sound transmission. The results of this study have significance for middle ear reconstructive surgery and the design of 3D-printed three-ossicle biocompatible prostheses.

3D printing↗
NASA NTRS2005

Ex Vivo Growth of Bioengineered Ligaments and Other Tissues

A method of growing bioengineered tissues for use in surgical replacement of damaged anterior cruciate ligaments has been invented. An anterior cruciate ligament is one of two ligaments (the other being the posterior cruciate ligament) that cross in the middle of a knee joint and act to prevent the bones in the knee from sliding forward and backward relative to each other. Anterior cruciate ligaments are frequently torn in sports injuries and traffic accidents, resulting in pain and severe limitations on mobility. By making it possible to grow replacement anterior cruciate ligaments that structurally and functionally resemble natural ones more closely than do totally synthetic replacements, the method could create new opportunities for full or nearly full restoration of functionality in injured knees. The method is also adaptable to the growth of bioengineered replacements for other ligaments (e.g., other knee ligaments as well as those in the hands, wrists, and elbows) and to the production of tissues other than ligaments, including cartilage, bones, muscles, and blood vessels. The method is based on the finding that the histomorphological properties of a bioengineered tissue grown in vitro from pluripotent cells within a matrix are affected by the direct application of mechanical force to the matrix during growth generation. This finding provides important new insights into the relationships among mechanical stress, biochemical and cell-immobilization methods, and cell differentiation, and is applicable to the production of the variety of tissues mentioned above. Moreover, this finding can be generalized to nonmechanical (e.g., chemical and electromagnetic) stimuli that are experienced in vivo by tissues of interest and, hence, the method can be modified to incorporate such stimuli in the ex vivo growth of replacements for the various tissues mentioned above. In this method, a three-dimensional matrix made of a suitable material is seeded with pluripotent stem cells. The patient s bone-marrow stromal cells are preferably used as the pluripotent cells in this method. Suitable matrix materials are materials to which cells can adhere for example, collagen type I. The seeded matrix is attached to anchors at opposite ends and then the cells in the matrix are cultured under conditions appropriate for the growth and regeneration of cells. Suitable anchor materials are materials to which the matrix can attach; examples include demineralized bone and Goinopra coral that has been treated to convert its calcium carbonate to calcium phosphate.

Altman, Gregory↗
NASA NTRS2003

Hindlimb unloading alters ligament healing

We investigated the hypothesis that hindlimb unloading inhibits healing in fibrous connective tissue such as ligament. Male rats were assigned to 3- and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing, and hindlimb-suspended healing. Ambulatory and suspended animals underwent surgical rupture of their medial collateral ligaments, whereas sham surgeries were performed on control animals. After 3 or 7 wk, mechanical and/or morphological properties were measured in ligament, muscle, and bone. During mechanical testing, most suspended ligaments failed in the scar region, indicating the greatest impairment was to ligament and not to bone-ligament insertion. Ligament testing revealed significant reductions in maximum force, ultimate stress, elastic modulus, and low-load properties in suspended animals. In addition, femoral mineral density, femoral strength, gastrocnemius mass, and tibialis anterior mass were significantly reduced. Microscopy revealed abnormal scar formation and cell distribution in suspended ligaments with extracellular matrix discontinuities and voids between misaligned, but well-formed, collagen fiber bundles. Hence, stress levels from ambulation appear unnecessary for formation of fiber bundles yet required for collagen to form structurally competent continuous fibers. Results support our hypothesis that hindlimb unloading impairs healing of fibrous connective tissue. In addition, this study provides compelling morphological evidence explaining the altered structure-function relationship in load-deprived healing connective tissue.

NASA Discipline Musculoskeletal↗
NASA NTRS2001

Bioengineered anterior cruciate ligament

The present invention provides a method for producing an anterior cruciate ligament ex vivo. The method comprises seeding pluripotent stem cells in a three dimensional matrix, anchoring the seeded matrix by attachment to two anchors, and culturing the cells within the matrix under conditions appropriate for cell growth and regeneration, while subjecting the matrix to one or more mechanical forces via movement of one or both of the attached anchors. Bone marrow stromal cells are preferably used as the pluripotent cells in the method. Suitable matrix materials are materials to which cells can adhere, such as a gel made from collagen type I. Suitable anchor materials are materials to which the matrix can attach, such as Goinopra coral and also demineralized bone. Optimally, the mechanical forces to which the matrix is subjected mimic mechanical stimuli experienced by an anterior cruciate ligament in vivo. This is accomplished by delivering the appropriate combination of tension, compression, torsion, and shear, to the matrix. The bioengineered ligament which is produced by this method is characterized by a cellular orientation and/or matrix crimp pattern in the direction of the applied mechanical forces, and also by the production of collagen type I, collagen type III, and fibronectin proteins along the axis of mechanical load produced by the mechanical forces. Optimally, the ligament produced has fiber bundles which are arranged into a helical organization. The method for producing an anterior cruciate ligament can be adapted to produce a wide range of tissue types ex vivo by adapting the anchor size and attachment sites to reflect the size of the specific type of tissue to be produced, and also adapting the specific combination of forces applied, to mimic the mechanical stimuli experienced in vivo by the specific type of tissue to be produced. The methods of the present invention can be further modified to incorporate other stimuli experienced in vivo by the particular developing tissue, some examples of the stimuli being chemical stimuli, and electro-magnetic stimuli. Some examples of tissue which can be produced include other ligaments in the body (hand, wrist, elbow, knee), tendon, cartilage, bone, muscle, and blood vessels.

Altman, Gregory↗
NASA NTRS1982

Knee-ligament loading properties as influenced by gravity. I - Junction with bone of 3-G rodents

The effect of 3-G conditions on the bone-to-ligament junctions of the knee is studied in rats. Results following chronic 3-G centrifugation of rats show that their bone-to-ligament junctions exhibited a force-sustaining capacity (F) which was 95 + or - 12% of the value for the control group. However, F was actually 29 + or - 5% greater for centrifuged rats than for control rats of comparable size, as the experimental animals grew to smaller body mass. It is concluded that gravity determines part of the magnitude of F, and therefore this value will probably be weaker after development in a weightless environment.

Wunder, C. C.↗
DOE OSTI2021

Nrf2 activation is involved in osteogenic differentiation of periodontal ligament stem cells under cyclic mechanical stretch

Highlights: • Cyclic mechanical stretch increases the nuclear accumulation of Nrf2 in PDLSCs. • T-BHQ promotes osteogenic differentiation under cyclic mechanical stretch. • Nrf2 activation may improve alveolar bone remodeling during orthodontic treatment. During orthodontic treatment, mechanical stretch serves a crucial function in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Up-regulated reactive oxygen species (ROS) level is a result of cyclic mechanical stretch in many cell types. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a master regulator in various antioxidants expression. However, it is not known whether cyclic mechanical stretch could induce the ROS generation in PDLSCs and whether Nrf2 participated in this process. The present study was aimed to investigate the role of Nrf2 in PDLSCs under cyclic mechanical stretch. Our results showed that cyclic mechanical stretch increased ROS level and the nuclear accumulation of Nrf2 during osteoblast differentiation. Knocking down Nrf2 by siRNA transfection increased ROS formation and suppressed osteogenic differentiation in PDLSCs. T-BHQ, a Nrf2 activator, promoted the osteogenic differentiation in PDLSCs under cyclic mechanical stretch, and improved the microstructure of alveolar bone during orthodontic tooth movement in rats by employing micro-CT system. Taken together, Nrf2 activation was involved in osteogenic differentiation under cyclic mechanical stretch in PDLSCs. T-BHQ could promote the osteogenic differentiation in vitro and in vivo, suggesting a promising option for the remodeling of the alveolar bone during orthodontic tooth movement.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Engineering hybrid textile braids for tendon and ligament repair application

Abstract Challenges involving tendon and ligament repair have motivated the investigation of new strategies to improve clinical outcomes. These have been mainly based on polymer constructs, which may be non‐biodegradable or biodegradable. The former typically fails due to lack of device integration and the latter demands a complex balance between biodegradability and tissue ingrowth, often failing due to insufficient mechanical properties. This work presents the development of hybrid braids based on polyethylene terephthalate (PET) and polylactic acid (PLA) yarns. A textile technique was used to fabricate braids based on 16 multifilament yarns of varying PLA/PET composition. The composition was varied to maximize biodegradability while ensuring mechanical performance. The braids' morphology, physical and mechanical properties were characterized. As production parameters and architecture were maintained, the braids exhibited similar porosity and wicking ability. The breaking force and stiffness decreased significantly as the number of PLA yarns increased, although strain levels remained constant. Braids containing 10 and 12 PET yarns (out of the total 16 yarns) demonstrated good creep and force‐relaxation behavior, as well as resistance to cyclic loading. These compositions were selected for future work, to be assembled into more elaborate structures to mimic the fibrous organization and tensile properties of different tendons/ligaments.

Peixoto, Tânia↗
DOE OSTI2021

Nanostructured ligament and fiber Al–doped Li 7 La 3 Zr 2 O 12 scaffolds to mediate cathode-electrolyte interface chemistry

In this study, scaffold structures of electrospun aluminum–substituted lithium lanthanum zirconate Li 7 La 3 Zr 2 O 12 (Al-LLZO) were synthesized and used as an additive in a LiNi 0.6 Mn 0.2 Co 0.2 O 2 composite cathode. The scaffolds were crystalized in the cubic phase after calcination at 700 °C. The Al-LLZO scaffold morphology was dependent on the precursor formulation (aqueous and dimethylformamide. The aqueous precursors resulted in scaffolds of densely coalesced ligaments, whereas the dimethylformamide precursors resulted in high–aspect ratio nanofiber scaffolds. The long-term cycling stability and rate performance of the cells were found to depend on the Al-LLZO scaffold morphology. The uniformly dispersed Al-LLZO fibers resulted in a more stable cathode electrolyte interface formation through the reduced decomposition of the LiPF 6 salt during cycling, resulting in a better high-rate and long-term cycling performance.

25 ENERGY STORAGE↗
DOE OSTI2020

“Figure‐of‐Eight” Suture‐Button Technique for Fixation of Displaced Anterior Cruciate Ligament Avulsion Fracture

Objective To assess the clinical results of the “figure‐of‐eight” suture‐button technique in the arthroscopic treatment of anterior cruciate ligament (ACL) tibial avulsion fractures. Methods This was a retrospective study reviewing data from September 2013 to June 2019. A total of 27 patients (13 males and 14 females) who underwent arthroscopic “figure‐of‐eight” suture‐button fixation for displaced ACL avulsion fractures were analyzed. The mean age of the patients in the sample was 15.8 years (10–29 years), with a mean follow‐up of 24 months (6–48 months). According to Meyers–McKeever classification, 11 patients were classified as type III and 16 as type IV. All patients were evaluated following the guidelines of the radiological union, the Lysholm knee scoring scale, and the International Knee Documentation Committee (IKDC). Results Fractures were united within 3 months after surgery in all 27 cases. During the last follow‐up, all the anterior drawer and Lachman tests were negative, except in 1 patient whose anterior drawer test was 1° positive. The range of motion was improved from 72.22° ± 27.92° before surgery to 137.78° ± 7.38° at the last follow‐up ( P < 0.05); the Lysholm score was improved from 45.81 ± 10.94 before surgery to 93.04 ± 5.66 at the last follow‐up ( P < 0.05); and the IKDC score was increased from 43.89 ± 11.16 before surgery to 90.26 ± 5.86 at the last follow‐up ( P < 0.05). In 1 patient, an inflammatory reaction was observed at the medial incision of the tibial tubercle; the symptoms disappeared with administration of antibiotics for 1 week. All patients returned to their preinjury physical activities at the last follow‐up. Conclusion The “figure‐of‐eight” suture‐button technique achieves a satisfactory clinical outcome and provides an effective method for the treatment of displaced ACL avulsion fractures.

Kuang, Shi‐da↗
DOE OSTI2021

Biomechanical Comparison of Anatomic Restoration of the Ulnar Footprint vs Traditional Ulnar Tunnels in Ulnar Collateral Ligament Reconstruction

Background: Current techniques for ulnar collateral ligament (UCL) reconstruction do not reproduce the anatomic ulnar footprint of the UCL. The purpose of this study was to describe a novel UCL reconstruction technique that utilizes proximal-to-distal ulnar bone tunnels to better re-create the anatomy of the UCL and to compare the biomechanical profile at time zero among this technique, the native UCL, and the traditional docking technique. Hypothesis: The biomechanical profile of the anatomic technique is similar to the native UCL and traditional docking technique. Study Design: Controlled laboratory study. Methods: Ten matched cadaveric elbows were potted with the forearm in neutral rotation. The palmaris longus tendon graft was harvested, and bones were sectioned 14 cm proximal and distal to the elbow joint. Specimen testing included (1) native UCL testing performed at 90° of flexion with 0.5 N·m of valgus moment preload, (2) cyclic loading from 0.5 to 5 N·m of valgus moment for 1000 cycles at 1 Hz, and (3) load to failure at 0.2 mm/s. Elbows then underwent UCL reconstruction with 1 elbow of each pair receiving the classic docking technique using either anatomic (proximal to distal) or traditional (anterior to posterior) tunnel locations. Specimen testing was then repeated as described. Results: There were no differences in maximum load at failure between the anatomic and traditional tunnel location techniques (mean ± SD, 34.90 ± 10.65 vs 37.28 ± 14.26 N·m; P = .644) or when including the native UCL (45.83 ± 17.03 N·m; P = .099). Additionally, there were no differences in valgus angle after 1000 cycles across the anatomic technique (4.58°± 1.47°), traditional technique (4.08°± 1.28°), and native UCL (4.07°± 1.99°). The anatomic group and the native UCL had similar valgus angles at failure (24.13°± 5.86° vs 20.13°± 5.70°; P = .083), while the traditional group had a higher valgus angle at failure when compared with the native UCL (24.88°± 6.18° vs 19.44°± 5.86°; P = .015). Conclusion: In this cadaveric model, UCL reconstruction with the docking technique utilizing proximal-to-distal ulnar tunnels better restored the ulnar footprint while providing valgus stability comparable with reconstruction with the docking technique using traditional anterior-to-posterior ulnar tunnel locations. These results suggest that utilization of the anatomic tunnel location in UCL reconstruction has similar biomechanical properties to the traditional method at the time of initial fixation (ie, not accounting for healing after reconstruction in vivo) while keeping the ulnar tunnels farther from the ulnar nerve. Further studies are warranted to determine if an anatomically based UCL reconstruction results in differing outcomes than traditional reconstruction techniques. Clinical Relevance: Current UCL reconstruction techniques do not accurately re-create the ulnar UCL footprint. The UCL is a dynamic constraint to valgus loads at the elbow, and a more anatomic reconstruction may afford more natural joint kinematics. This more anatomic technique performs similarly to the traditional docking technique at time zero, and the results of this study may offer a starting point for future in vivo studies.

Chang, Edward S.↗
DOE OSTI2022

Effect of High-Protein Diets on Integrated Myofibrillar Protein Synthesis before Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Pilot Study

Increasing dietary protein intake during periods of muscle disuse may mitigate the resulting decline in muscle protein synthesis (MPS). The purpose of this randomized pilot study was to determine the effect of increased protein intake during periods of disuse before anterior cruciate ligament (ACL) reconstruction on myofibrillar protein synthesis (MyoPS), and proteolytic and myogenic gene expression. Six healthy, young males (30 ± 9 y) were randomized to consume a high-quality, optimal protein diet (OP; 1.9 g·kg−1·d−1) or adequate protein diet (AP; 1.2 g·kg−1·d−1) for two weeks before ACL reconstruction. Muscle biopsies collected during surgery were used to measure integrated MyoPS during the intervention (via daily deuterium oxide ingestion) and gene expression at the time of surgery. MyoPS tended to be higher, with a large effect size in OP compared to AP (0.71 ± 0.1 and 0.54 ± 0.1%·d−1; p = 0.076; g = 1.56). Markers of proteolysis and myogenesis were not different between groups (p > 0.05); however, participants with greater MyoPS exhibited lower levels of MuRF1 gene expression compared to those with lower MyoPS (r = −0.82, p = 0.047). The data from this pilot study reveal a potential stimulatory effect of increased daily protein intake on MyoPS during injury-mediated disuse conditions that warrants further investigation.

Howard, Emily E. (ORCID:0000000179791236)↗
NASA NTRS1981

Reissner's membrane and the spiral ligament in normal rats and those treated with ethacrynic acid

A description is presented of recent ultrastructural findings in Reissner's membrane and the spiral ligament in rats treated daily with ethacrynic acid during the 2nd and 3rd weeks of postnatal life, a period of final maturation of the inner ear and its fluids. A distension of Reissner's membrane in every cochlear turn, indicative of mild endolymphatic hydrops, was found to occur in animals that received a higher dose of ethacrynic acid. Ultrastructurally, the cytoplasm of the epithelial cells of Reissner's membrane showed increased electron density after treatment with ethacrynic acid. This increase was most pronounced in animals treated with a greater quantity of the drug. The epithelial cells had similar ultracellular features throughout except that the cells were much thinner in the region of maximal distension.

Ross, M. D.↗
NASA NTRS1986

Osteoblast histogenesis in periodontal ligament and tibial metaphysis during simulated weightlessness

Utilizing the nuclear morphometric assay for osteoblast histogenesis, the effect of simulated weightlessness (SW) on the relative numbers of the periodontal ligament (PDL) osteoblast progenitors and on the total number of osteogenic cells was determined in rats. Weightlessness was simulated by subjecting rats to continuous 30-deg head-down posture using a modified back-harness device of Morey (1979). The response of a partially unloaded, weight-bearing bone, tibial primary spongiosa (PS), was compared to a normally loaded, nonweight-bearing PDL bone. Data indicated a similar differentiation sequence in PS and PDL, which suggests that these bones might be sensitive to the same systemic factors. Preosteoblast numbers were seen to decrease in both nonweight-bearing and weight-bearing bones during SW (compared with rats not exposed to SW), indicating the importance of systemic mediators, such as cephalad fluid shift, physiological stress, and/or growth retardation.

Fielder, Paul J.↗
NASA NTRS1987

Nuclear morphometric analysis of osteoblast precursor cells in periodontal ligament, SL-3 rats

Five small (55 days old, 196 +/- 5 g) (mean +/- SE) and five large (83 days old, 382 +/- 4 g) Sprague-Dawley strain, specific pathogen-free rats were exposed to a 7-day spaceflight and 12-h postflight recovery period. As measured in 3-micron sections, periodontal ligament (PDL) fibroblastlike cells were classified according to nuclear size: A + A' (40-79), B (80-119), C (120-169), and D (greater than or equal to 170 microns 3). Since the histogenesis sequence is A----A'----C----D----osteoblast, the relative incidence of A + A' to C + D is an osteogenic index. No difference in A + A' or C + D cells in small rats may reflect partial recovery of preosteoblast formation (A----C) during the 12-h postflight period. Large flight rats demonstrated increased numbers of A + A', indicating an inhibition of preosteoblast formation (A----C). At least in the older group, a 7-day flight is adequate to reduce PDL osteogenic potential (inhibition in PDL osteoblast differentiation and/or specific attrition of C + D cells) that does not recover by 12-h postflight.

Flight Experiment↗
NASA NTRS1990

Experiment K-6-03. Gravity and skeletal growth, part 1. Part 2: Morphology and histochemistry of bone cells and vasculature of the tibia; Part 3: Nuclear volume analysis of osteoblast histogenesis in periodontal ligament cells; Part 4: Intervertebral disc swelling pressure associated with microgravity

Bone area, bone electrophysiology, bone vascularity, osteoblast morphology, and osteoblast histogenesis were studied in rats associated with Cosmos 1887. The results suggest that the synchronous animals were the only group with a significantly larger bone area than the basal group, that the bone electrical potential was more negative in flight than in the synchronous rats, that the endosteal osteoblasts from flight rats had greater numbers of transitional Golgi vesicles but no difference in the large Golgi saccules or the alkaline phosphatase activity, that the perioteal vasculature in the shaft of flight rats often showed very dense intraluminal deposits with adjacent degenerating osteocytes as well as lipid accumulations within the lumen of the vessels and sometimes degeneration of the vascular wall (this change was not present in the metaphyseal region of flight animals), and that the progenitor cells decreased in flight rats while the preosteoblasts increased compared to controls. Many of the results suggest that the animals were beginning to recover from the effects of spaceflight during the two day interval between landing and euthanasia; flight effects, such as the vascular changes, did not appear to recover.

Holton, E.↗