Ligament Tissue Research Articles

Nanometer materials and the repairing function of ligament injury in basketball

Basketball has always been a favorite sport for many young people, but ligament injuries often occur during basketball, which will also affect the progress of many sports games. This study focuses on the effects of nanomaterials on the repair of basketball ligament injuries, mainly through tissue engineering to repair ligaments. First, HA nanocomposites are prepared by dissolving P (LLA-Cl) and collagen in hexagonal fluoropropanol. Samples were scanned and analyzed using a high-resolution micro-CT system. Scanning electron microscope (SEM) was used to examine the microstructure, chemical structure and thermal stability of the composite biomaterial. The ligament maturity is evaluated by measuring ligament growth (Tb.N). In vitro cell culture technique was used to inoculate bone marrow mesenchymal stem cells on the cultured nanomaterials, and the adhesion and proliferation of cells were observed with confocal microscope and SEM. The ability of bone marrow mesenchymal stem cells to secrete extracellular calcium matrix is determined by alcohol phosphatase (ALP) and calcium ion content. Using RT-PCR and immunohistology, bone formation and ligament differentiation of bone marrow mesenchymal stem cells were detected. Nanomaterials show extremely high compatibility with damaged ligament tissue, Lysholm score increased from 43.2 ± 2.4 points (30–88 points) before surgery to 96 ± 2.0 points (72–100 points) after surgery (p < 0.001). The research results show that nanocomposite materials combined with tissue engineering can obviously promote the repair of ligaments.

STORAGE MEDIUM FOR AVULSED TEETH: A LITERATURE REVIEW

Avulsion injury is one of the most severe types of traumatic dental injuries. Following avulsion, periodontal ligament tissues are injured and the vessels and nerves of the pulp rupture at the apical foramen which causes pulp necrosis. In studies it was reported that the key to retention of the knocked-out teeth was to maintain the viability of the periodontal ligament. Storage media plays an important role in preserving the viability of PDL cells during extra alveolar time. This article highlights the different storage medias available for avulsed teeth, along with their merits and demerits.

Spatial Controls of Ligamentous Tissue Orientations Using the Additively Manufactured Platforms in an In Vivo Model: A Pilot Study

The periodontal ligaments (PDLs) with specific orientations to tooth-root surfaces play a key role in generating biomechanical responses between the alveolar bone and cementum as a tooth-supporting tissue. However, control of angulations and regeneration of the ligamentous tissues within micron-scaled interfaces remains challenging. To overcome this limitation, this study investigated surface fabrications with microgroove patterns to control orientations of rat PDL cells in vitro and fibrous tissues in vivo. After being harvested, rat PDL cells were cultured and three different microgroove patterns (∠PDL groove = 0°, ∠PDL groove = 45°, and ∠PDL groove = 90°) were created by the digital slicing step in 3D printing. Cell-seeded scaffolds were subcutaneously transplanted at 3 and 6 weeks. In histology images, rat PDL cells were spatially controlled to angularly organize following the microgroove patterns and fibrous tissues were formed in scaffolds with specific angulations, which were reflected by additively manufactured microgroove topographies. Based on the results, specifically characterized surface topographies were significant to directly/indirectly organizing rat PDL cell alignments and fibrous tissue orientations. Therefore, interactions between surface topographies and tissue organizations could be one of the key moderators for the multiple tissue complex (bone-ligament-cementum) neogenesis in periodontal tissue engineering.

The research progress of bionic scaffolds in ligament tissue engineering

Ligaments are dense fibrous connective tissue that maintains joint stability through bone-to-bone connections. Ligament tears that due to sports injury or tissue aging usually require surgical intervention, and transplanting autologous, allogeneic, or artificial ligaments for reconstruction is the gold standard for treating such diseases in spite of many drawbacks. With the development of materialogy and manufacturing technology, engineered ligament tissue based on bioscaffold is expected to become a new substitute, which can lead to tissue regeneration by simulating the structure, composition, and biomechanical properties of natural tissue. This paper reviewed some recently published in vitro and animal researches focusing on ligament tissue engineering, then evaluated the properties and the effects on tissue repair and reconstruction of fiber structure scaffolds, multi-phase interface scaffolds and bio-derived scaffolds designed by bionic principle and made of different materials, manufacturing techniques and biological factors. Finally, summarization followed by the prospection for future development direction of biological scaffolds in ligament tissue engineering research is given.

4-Methylumbelliferone suppresses catabolic activation in anterior cruciate ligament-derived cells via a mechanism independent of hyaluronan inhibition

BackgroundThe anterior cruciate ligament (ACL) has a key role as a dynamic stabilizer of the knee joints, and ACL dysfunction caused by traumatic or degenerative rupture accelerates osteoarthritis progression. Thus, it is important to prevent the degenerative rupture of the ACL. 4-Methylumbelliferone (4-MU), a pre-approved drug, exerts anti-inflammatory effects in osteoarthritis chondrocytes. It was originally used as an inhibitor of hyaluronan synthesis in chondrocytes.MethodsIn this study, we investigated whether 4-MU affects the expression of catabolic factors, such as matrix metalloproteinase (MMP)-1, MMP-3, and interleukin (IL)-6, in ACL-derived cells and ACL explant cultures using immunohistochemistry, real-time RT-qPCR, and capillary western immunoassay. Furthermore, the hyaluronan concentration was evaluated using a colorimetric assay. Statistical analyses were conducted using analysis of variance for multi-group comparisons, followed by Tukey or Tukey-Kramer post hoc test.ResultsOur results revealed, for the first time, that 4-MU suppressed the IL-β-induced upregulation of pro-catabolic factors, such as MMP-1, MMP-3, and IL-6, in ACL-derived cells. This suppressive effect was also observed in the cultured ligament tissues in ex vivo experiments. 4-MU also reversed an enhanced dependence on glycolysis in IL-1β-activated ACL-derived cells. Furthermore, we found that the suppressive effects of 4-MU were exerted directly and not through the inhibition of hyaluronan synthesis.ConclusionsWe conclude that 4-MU could be an effective and useful treatment for knee osteoarthritis, owing to its anti-inflammatory effect on, not only chondrocytes but also on ligament cells.

PPARγ-Induced Global H3K27 Acetylation Maintains Osteo/Cementogenic Abilities of Periodontal Ligament Fibroblasts.

The periodontal ligament is a soft connective tissue embedded between the alveolar bone and cementum, the surface hard tissue of teeth. Periodontal ligament fibroblasts (PDLF) actively express osteo/cementogenic genes, which contribute to periodontal tissue homeostasis. However, the key factors maintaining the osteo/cementogenic abilities of PDLF remain unclear. We herein demonstrated that PPARγ was expressed by in vivo periodontal ligament tissue and its distribution pattern correlated with alkaline phosphate enzyme activity. The knockdown of PPARγ markedly reduced the osteo/cementogenic abilities of PDLF in vitro, whereas PPARγ agonists exerted the opposite effects. PPARγ was required to maintain the acetylation status of H3K9 and H3K27, active chromatin markers, and the supplementation of acetyl-CoA, a donor of histone acetylation, restored PPARγ knockdown-induced decreases in the osteo/cementogenic abilities of PDLF. An RNA-seq/ChIP-seq combined analysis identified four osteogenic transcripts, RUNX2, SULF2, RCAN2, and RGMA, in the PPARγ-dependent active chromatin region marked by H3K27ac. Furthermore, RUNX2-binding sites were selectively enriched in the PPARγ-dependent active chromatin region. Collectively, these results identified PPARγ as the key transcriptional factor maintaining the osteo/cementogenic abilities of PDLF and revealed that global H3K27ac modifications play a role in the comprehensive osteo/cementogenic transcriptional alterations mediated by PPARγ.

The impact of cryopreservation in signature markers and immunomodulatory profile of tendon and ligament derived cells.

Tendon and ligament (T/L) engineering strategies towards clinical practice have been challenged by a paucity of understanding in the identification and still poorly described characterization of cellular niches. Prospecting how resident cell populations behave in vitro, and how cryopreservation may influence T/ L-promoting factors, can provide insights intoT/ L-cellular profiles for novel regenerative solutions. Therefore, we studiedhuman T/ L-derived cells isolated from patellar tendons and cruciate ligaments as suitable cellular models to anticipate tendon and ligament niches responses for advanced strategies with predictive tenogenic and ligamentogenic value. Our results show that the crude populations isolated from tendon and ligament tissues hold a stem cell subset and share a similar behavior in terms of tenogenic/ligamentogenic commitment. Both T/ L-derived cells successfully undergo cryopreservation/thawing maintaining the tenogenic/ligamentogenic profiles. The major differences between cryopreserved and fresh populations were observed at the gene expression of MKX, SCX, and TNMD as well as at the protein levels of collagen type I and III, in which cells from tendon origin (hTDCs) evidence increased values in comparison to the ones from ligament (hLDCs, p < 0.05). In addition, low-temperature storage was shown to potentiate an immunomodulatory profile of cells, especially in hTDCs leading to an increase in the gene expression of the anti-inflammatory factors IL-4 and IL-10 (p < 0.05), as well as in the protein secretion of IL-10 (p < 0.01) and IL-4 (p < 0.001). Overall, the outcomes highlight the relevance of the cryopreserved T/ L-derived cells and their promising immunomodulatory cues as in vitro models for investigating cell-mediated mechanisms driving tissue healing and regeneration.

Biomimetic Biphasic Electrospun Scaffold for Anterior Cruciate Ligament Tissue Engineering.

Replacing damaged anterior cruciate ligaments (ACLs) with tissue-engineered artificial ligaments is challenging because ligament scaffolds must have a multiregional structure that can guide stem cell differentiation. Here, we designed a biphasic scaffold and evaluated its effect on human marrow mesenchymal stem cells (MSCs) under dynamic culture conditions as well as rat ACL reconstruction model in vivo. We designed a novel dual-phase electrospinning strategy wherein the scaffolds comprised randomly arranged phases at the two ends and an aligned phase in the middle. The morphological, mechanical properties and scaffold degradation were investigated. MSCs proliferation, adhesion, morphology and fibroblast markers were evaluated under dynamic culturing. This scaffold were tested if they could induce ligament formation using a rodent model in vivo. Compared with other materials, poly(D,L-lactide-co-glycolide)/poly(ε-caprolactone) (PLGA/PCL) with mass ratio of 1:5 showed appropriate mechanical properties and biodegradability that matched ACLs. After 28days of dynamic culturing, MSCs were fusiform oriented in the aligned phase and randomly arranged in a paving-stone-like morphology in the random phase. The increased expression of fibroblastic markers demonstrated that only the alignment of nanofibers worked with mechanical stimulation to promote effective fibroblast differentiation. This scaffold was a dense collagenous structure, and there was minimal difference in collagen direction in the orientation phase. Dual-phase electrospun scaffolds had mechanical properties and degradability similar to those of ACLs. They promoted differences in the morphology of MSCs and induced fibroblast differentiation under dynamic culture conditions. Animal experiments showed that ligamentous tissue regenerated well and supported joint stability.

ILC1s and ILC3s Exhibit Inflammatory Phenotype in Periodontal Ligament of Periodontitis Patients.

Innate lymphoid cells (ILCs) are emerging as important players in inflammatory diseases. The oral mucosal barrier harbors all ILC subsets, but how these cells regulate the immune responses in periodontal ligament tissue during periodontitis remains undefined. Here, we show that total ILCs are markedly increased in periodontal ligament of periodontitis patients compared with healthy controls. Among them, ILC1s and ILC3s, particularly NKp44+ILC3 subset, are the predominant subsets accumulated in the periodontal ligament. Remarkably, ILC1s and ILC3s from periodontitis patients produce more IL-17A and IFN-γ than that from healthy controls. Collectively, our results highlight the role of ILCs in regulating oral immunity and periodontal ligament inflammation and provide insights into targeting ILCs for the treatment of periodontitis.

Transthyretin: From Structural Stability to Osteoarticular and Cardiovascular Diseases.

Transthyretin (TTR) is a tetrameric protein transporting hormones in the plasma and brain, which has many other activities that have not been fully acknowledged. TTR is a positive indicator of nutrition status and is negatively correlated with inflammation. TTR is a neuroprotective and oxidative-stress-suppressing factor. The TTR structure is destabilized by mutations, oxidative modifications, aging, proteolysis, and metal cations, including Ca2+. Destabilized TTR molecules form amyloid deposits, resulting in senile and familial amyloidopathies. This review links structural stability of TTR with the environmental factors, particularly oxidative stress and Ca2+, and the processes involved in the pathogenesis of TTR-related diseases. The roles of TTR in biomineralization, calcification, and osteoarticular and cardiovascular diseases are broadly discussed. The association of TTR-related diseases and vascular and ligament tissue calcification with TTR levels and TTR structure is presented. It is indicated that unaggregated TTR and TTR amyloid are bound by vicious cycles, and that TTR may have an as yet undetermined role(s) at the crossroads of calcification, blood coagulation, and immune response.

Role and mechanism of low-dose lipopolysaccharide-treated human periodontal ligament stem cells on the expression of macrophage pro-inflammatory factors

Objective: To investigate the effect of low dose lipopolysaccharide (LPS)-treated human periodontal ligament stem cells (HPDLSC) on the expression of macrophage pro-inflammatory factors and the mechanism involved. Methods: The primary HPDLSCs were obtained from healthy third molar periodontal ligament tissue. Phosphate buffer saline (PBS), 100 μg/L or 10 mg/L of LPS were used to treat HPDLSCs for 48 h, and their conditioned media were respectively co-cultured with THP-1-derived macrophages for 48 h. The corresponding experimental groups were PBS-treated HPDLSC-derived conditioned medium (CM-C) group, low dose LPS-treated HPDLSC-derived conditioned medium (CM-L) group, and high dose LPS-treated HPDLSC-derived conditioned medium (CM-H) group. Quantitative real-time PCR was performed to explore the mRNA expressions of macrophage interleukin (IL)-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α) in the CM-C, CM-L and CM-H groups, and the expressions of nuclear factor (erythroid-derived 2)-like 2 (NRF2), glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H quinone dehydrogenase 1 (NQO1) and heme oxygenase 1 (HO-1) in the CM-C and CM-L groups. Meanwhile, Western blotting was used to detect the change of nuclear and cytoplasmic NRF2 and the levels of GCLC and HO-1 in the CM-C and CM-L groups. The 2', 7'-dichlorofluorescein probe was adopted to detect the reactive oxygen species (ROS) levels of macrophages in the CM-C and CM-L groups and the data were characterized by the mean fluorescent intensity (MFI). Results: The mRNA expressions of macrophage pro-inflammatory factors IL-6, IL-8, IL-12 and TNF-α in the CM-H group (2.332±0.594, 3.601±0.639, 2.120±0.677 and 2.468±0.236) were significantly upregulated compared with those in the CM-C group (1.000±0.321, 1.000±0.151, 1.000±0.059 and 1.000±0.095) (P<0.05); while the relative mRNA levels of IL-6, IL-12 and TNF-α in the CM-L group (0.056±0.002, 0.215±0.024 and 0.567±0.071) were much lower than those in the CM-C group (1.000±0.209, 1.000±0.220 and 1.000±0.220) (P<0.05). At the mRNA level, the expression of NRF2 was significantly increased in the CM-L group (1.864±0.198) compared with that in the CM-C group (1.000±0.094) (P<0.05). At the protein level, the cytoplasmic NRF2 and nuclear NRF2 were increased in CM-L group (1.175±0.104 and 1.308±0.082) compared with those in the CM-C group (1.000±0.025 and 1.000±0.049) (P<0.05). Furthermore, the antioxidative genes, i.e. GCLC and NQO1, localized in NRF2 downstream, were significantly upregulated in the CM-L group (1.786±0.278 and 1.444±0.078) compared with the CM-C group (1.000±0.139 and 1.000±0.226) (P<0.05). The protein levels of GCLC and HO-1 were augmented in the CM-L group (1.159±0.036 and 1.412±0.075) in contrast with those in the CM-C group (1.000±0.050 and 1.000±0.013) (P<0.05). In addition, the MFI in the CM-L group (123 419±1 302) was significantly lower than that in the CM-C group (139 193±1 241) (P<0.05). Conclusions: Low-dose LPS-treated HPDLSCs could regulate oxidative stress response through activating the NRF2 signaling pathway of macrophages and further downregulating the expressions of macrophage pro-inflammatory factors.

Short review on formulation of the bioinks for tendon and ligament 3D bioprinting

This review focuses on advances in the field of tendon bioprinting and ligament tissue engineering, as well as a discussion of the various mechanisms underlying the tendon and ligament tissue. All methods (cellular, non-cellular and both) aim to find complex living tissues capable of growing and maturing, using the same basic technology. To date, co-printing of cellular and non-cellular material has been identified as the most promising method for muscle applications because materials with good performance and good mechanical strength can be integrated within the same structure. Bioprinting publications for tendon and ligament applications are a developing field, and a detailed discussion of current challenges and future ideas is also presented in this review.

3D Electrospun Nanofiber-Based Scaffolds: From Preparations and Properties to Tissue Regeneration Applications.

Electrospun nanofibers have been frequently used for tissue engineering due to their morphological similarities with the extracellular matrix (ECM) and tunable chemical and physical properties for regulating cell behaviors and functions. However, most of the existing electrospun nanofibers have a closely packed two-dimensional (2D) membrane with the intrinsic shortcomings of limited cellular infiltration, restricted nutrition diffusion, and unsatisfied thickness. Three-dimensional (3D) electrospun nanofiber-based scaffolds can provide stem cells with 3D microenvironments and biomimetic fibrous structures. Thus, they have been demonstrated to be good candidates for in vivo repair of different tissues. This review summarizes the recent developments in 3D electrospun nanofiber-based scaffolds (ENF-S) for tissue engineering. Three types of 3D ENF-S fabricated using different approaches classified into electrospun nanofiber 3D scaffolds, electrospun nanofiber/hydrogel composite 3D scaffolds, and electrospun nanofiber/porous matrix composite 3D scaffolds are discussed. New functions for these 3D ENF-S and properties, such as facilitated cell infiltration, 3D fibrous architecture, enhanced mechanical properties, and tunable degradability, meeting the requirements of tissue engineering scaffolds were discovered. The applications of 3D ENF-S in cartilage, bone, tendon, ligament, skeletal muscle, nerve, and cardiac tissue regeneration are then presented with a discussion of current challenges and future directions. Finally, we give summaries and future perspectives of 3D ENF-S in tissue engineering and clinical transformation.

A finite-strain micromechanical model for the hyperelasticity of tendons and ligaments with crimped fibers

The hyperelasticity of soft biological tissues such as tendons and ligaments is closely related to their microstructures consisting of wavy fibers embedded in a soft matrix. Large deformation of such composites involves both microstructural evolution and material nonlinearity, posing a challenge of theoretical analysis. In this paper, we propose a finite-strain micromechanical method to predict the hyperelastic constitutive relation of tendons and ligaments reinforced with crimped fibers. The Mori–Tanaka method is extended to account for the interaction of wavy fibers embedded in a soft matrix under large deformation. It is found that the tension–shear coupling mechanism induced by fiber–matrix interaction is crucial for the nonlinear behavior of tendons and ligaments. The hyperelasticity of such composites relies strongly on the initial crimp shape, Young's modulus, and volume fraction of fibers. This model is validated by finite element simulations of a unit cell model with crimped fibers. Furthermore, an explicit expression based on dimensional analysis is derived for the hyperelastic constitutive relation in terms of microstructural and material parameters, and it fits well with experimental data of tendons at different ages. This study can not only deepen the understanding of the mechanical behaviors of such soft tissues of tendons and ligaments, but also help the optimal design of biomimetic composites with superior elasticity.

The importance of Böhler's angle in calcaneus geometry: A finite element model study.

Objectives Calcaneal fractures are the most common tarsal fractures following a foot-ankle trauma. The Böhler’s angle is an important measurable angle before, during, and after surgery. In this study, we aimed to investigate correlation between Böhler’s angle, calcaneal strength, and subtalar joint stress using a finite element analysis (FEA).Patients and methods Between January 2016 and December 2016, computed tomography (CT) scans were used with MIMICS® software for FEA. The ankle and foot of a 23-year-old male person with a height of 180 cm and weighing 80 kg was modeled as reference. Raw coronal CT images were obtained in Digital Imaging and Communications in Medicine format with the resolution of 512X512 pixels and 0.3-mm slice intervals in 135 kV. The structures including tibia, fibula and 26 other bones (talus, calcaneus, cuboid, navicular, three cuneiforms, five metatarsals, and 14 components of phalanges), cartilage and ligamentous tissues were modeled to form ankle joint. After determining Böhler’s angle as 35 degrees for the reference model, a fracture line was created on calcaneus. Calcaneus was remodeled with the Böhler’s angle of 45, 40, 30, 25, 20, 10, and 0 degrees respectively. All models were transferred to ANSYS software for FEA and the loads on the lower extremities with normal posture were applied on models.Results Analysis of all models based in the reference model revealed that maximum tension values on calcaneus increased, while the Böhler’s angle decreased, indicating a statistically significant difference. The decreased Böhler’s angle indicated statistically significantly higher maximum tension values (p=0.04). Action force in subtalar joint was evaluated by comparing with the forces in reference model. The increased Böhler’s angle was found to be associated with statistically significantly decreased amount of load on subtalar joint. The decreased Böhler’s angle was related to the statistically significantly increased amount of load on subtalar joint.Conclusion Our study results suggest that decreased Böhler’s angle increases the possibility of subtalar arthrosis, although overcorrection of the Böhler’s angle seems not to increase the risk of subtalar arthrosis.

Stress-Relaxation and CRE Behavior of Multi-Layer Silk Fibroin Yarns as a Scaffold in Tendon and Ligament Tissue Engineering

Stress-Relaxation and CRE Behavior of Multi-Layer Silk Fibroin Yarns as a Scaffold in Tendon and Ligament Tissue Engineering

Age-related type I collagen modifications reveal tissue-defining differences between ligament and tendon

Tendons and ligaments tend to be pooled into a single category as dense elastic bands of collagenous connective tissue. They do have many similar properties, for example both tissues are flexible cords of fibrous tissue that join bone to either muscle or bone. Tendons and ligaments are both prone to degenerate and rupture with only limited capacity to heal, although tendons tend to heal faster than ligaments. Type I collagen constitutes about 80% of the dry weight of tendons and ligaments and is principally responsible for the core strength of each tissue. Collagen synthesis is a complex process with multiple steps and numerous post-translational modifications including proline and lysine hydroxylation, hydroxylysine glycosylation and covalent cross-linking. The chemistry, placement and quantity of intramolecular and intermolecular cross-links are believed to be key contributors to the tissue-specific variations in material strength and biological properties of collagens. As tendons and ligaments grow and develop, the collagen cross-links are known to chemically mature, strengthen and change in profile. Accordingly, changes in cross-linking and other post-translational modifications are likely associated with tissue development and degeneration. Using mass spectrometry, we have compared tendon and ligaments from fetal and adult bovine knee joints to investigate changes in collagen post-translational properties. Although hydroxylation levels at the type I collagen helical cross-linking lysine residues were similar in all adult tissues, ligaments had significantly higher levels of glycosylation at these sites compared to tendon. Differences in lysine hydroxylation were also found between the tissues at the telopeptide cross-linking sites. Total collagen cross-linking analysis, including mature trivalent cross-links and immature divalent cross-links, revealed unique cross-linking profiles between tendon and ligament tissues. Tendons were found to have a significantly higher frequency of smaller diameter collagen fibrils compared with ligament, which we suspect is functionally associated with the unique cross-linking profile of each tissue. Understanding the specific molecular characteristics that define and distinguish these specialized tissues will be important to improving the design of orthopedic treatment approaches.

Augmented Spring Ligament Repair in Pes Planovalgus Reconstruction

Patients with pes planovalgus deformity often have coexisting spring ligament pathology. A primary repair of the ligament may fail during weightbearing due to chronic degeneration of the ligamentous tissue. Augmentation with a suture tape has been suggested to strengthen the repair. Limited data exist regarding flatfoot reconstruction with augmented spring ligament repair using a suture tape. This is a review of 57 consecutive patients who had flatfoot reconstruction with concomitant spring ligament augmented repair between July 2014 and August 2017. Weightbearing radiographic parameters were obtained preoperatively and compared to radiographs at an average time of 62 ± 46.5 (range 20-220) weeks postoperative. Significant improvements were seen in the radiographic parameters evaluated. Five patients had subsequent operations including one deep infection, 2 hardware removals remote to the spring ligament augmentation, 1 ankle arthrodesis, and 1 triple arthrodesis. Concomitant spring ligament repair augmented with a suture tape was a safe procedure that contributed to radiographic correction in a consecutive series of 57 patients undergoing flatfoot deformity correction.

Matrix metalloproteinases and Th17 cytokines in the gingival crevicular fluid during orthodontic tooth movement.

Matrix metalloproteinases (MMPs) contribute to remodeling in orthodontic tooth movement (OTM). Moreover, IL-17 can promote the production of MMPs. This study aimed to investigate the regulation of Th17 on MMPs expression during OTM. Eighteen children undergoing orthodontic treatment were recruited. The gingival crevicular fluid (GCF) was collected at different time points: the day of application (T0), one hour (T1), 24 hours (T2), one week (T3), 4 weeks (T4) and 12 weeks (T5) after the application of orthodontic force. Th17 cell-related cytokines and MMPs expression were measured in GCF by Multiplex Luminex analyser. Human periodontal ligament (hPDL) tissues were stimulated by IL-17. The levels of IL-17 and MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13) of the study teeth at T2-T4 were significantly up-regulated compared with that of T0 and T1 and decreased to baseline level at T5. We found that the expression of IL-17 was correlated with MMPs. After rhIL-17 treatment, the expression of MMP-1, MMP-2, and MMP-9 were up-regulated significantly. The IL-17 expression was positively correlated with MMPs. IL-17 promotes the expression of MMP-1, MMP-2, and MMP-9 by hPDL cells, suggesting that IL-17 plays a crucial role in the remodeling during OTM.

Ligamentous healing potential of the acromioclavicular ligament following acute anatomical reconstruction

BackgroundHorizontal instability following acute acromioclavicular joint (ACJ) reconstruction still occurs with a high prevalence. Although the human acromioclavicular ligament complex (ACLC) represents the major horizontal ACJ stabilizer, experimental studies on healing characteristics are lacking. Therefore, the purpose of this histological study was to investigate the healing potential of the ACLC following acute anatomical reconstructionMethodsIn this prospective clinical-experimental study, 28 ACLC biopsies were performed in patients with complete ACJ dislocations (Rockwood type 4 or 5) during acute hook plate stabilization (IG: implantation group; n = 14) and hook plate removal (EG: explantation group; n = 14). Histological analyses included Giemsa staining, polarized light microscopy and immunostaining against CD68, αSMA and collagen type I and type III. Histomorphological evaluation entailed cell counts, collagen expression score, ligament tissue maturity index (LTMI) and descriptive analysis of specific ligamentous structures. Statistics consisted of nonparametric Mann–Whitney U tests and a level of significance of P < .05.ResultsTotal cell counts (cells/mm2 1491 ± 296 vs. 635 ± 430; P < 0.001) and collagen III expression (3.22 ± 0.22 vs. 1.78 ± 0.41; P < 0.001) were higher in EG compared to IG. Inversely αSMA + (11 ± 9 vs. 179 ± 186; P < 0.001) and CD68 + cell counts (56 ± 20 vs. 100 ± 57; P 0.009) were significantly lower in the EG. The EG revealed a comparable reorientation of ligamentous structures. Consistently, ACLC samples of the EG (21.6 ± 2.4) displayed a high total but differently composed LTMI score (IG: 24.5 ± 1.2; P < 0.001).ConclusionsThis experimental study proved the ligamentous healing potential of the human ACLC following acute anatomical reconstruction. Histomorphologically, the ACLC reliably showed a ligamentous state of healing at a mean of about 12 weeks after surgery. However, processes of ligamentous remodeling were still evident. These experimental findings support recent clinical data showing superior horizontal ACJ stability with additional AC stabilization in the context of acute ACJ reconstruction. Though, prospective clinical and biomechanical studies are warranted to evaluate influencing factors on ACLC healing and potential impacts of acute ACLC repair on clinical outcome.Study typeControlled Laboratory Study