Anterolateral rotatory instability in vivo correlates tunnel position after anterior cruciate ligament reconstruction using bone-patellar tendon-bone graft

AIM To quantitatively assess rotatory and anterior-posterior instability in vivo after anterior cruciate ligament(ACL) reconstruction using bone-patellar tendon-bone(BTB) autografts, and to clarify the influence of tunnel positions on the knee stability.METHODS Single-bundle ACL reconstruction with BTB autograft was performed on 50 patients with a mean age of 28 years using the trans-tibial(TT)(n = 20) and trans-portal(TP)(n = 30) techniques. Femoral and tibial tunnel positions were identified from the high-resolution 3 D-CT bone models two weeks after surgery. Anterolateral rotatory translation was examined using a Slocum anterolateral rotatory instability test in open magnetic resonance imaging(MRI) 1.0-1.5 years after surgery, by measuring anterior tibial translation at the medial and lateral compartments on its sagittal images. Anterior-posterior stability was evaluated with a Kneelax3 arthrometer.RESULTS A total of 40 patients(80%) were finally followed up. Femoral tunnel positions were shallower(P < 0.01) and higher(P < 0.001), and tibial tunnel positions were more posterior(P < 0.05) in the TT group compared with the TP group. Anterolateral rotatory translations in reconstructed knees were significantly correlated with the shallow femoral tunnel positions(R = 0.42, P < 0.01), and the rotatory translations were greater in the TT group(3.2 ± 1.6 mm) than in the TP group(2.0 ± 1.8 mm)(P < 0.05). Side-to-side differences of Kneelax3 arthrometer were 1.5 ± 1.3 mm in the TT, and 1.7 ± 1.6 mm in the TP group(N.S.). Lysholm scores, KOOS subscales and reinjury rate showed no difference between the two groups.CONCLUSION Anterolateral rotatory instability significantly correlated shallow femoral tunnel positions after ACL reconstruction using BTB autografts. Clinical outcomes, rotatory and anterior-posterior stability were overall satisfactory in both techniques, but the TT technique located femoral tunnels in shallower and higher positions, and tibial tunnels in more posterior positions than the TP technique, thus increased the anterolateral rotation. Anatomic ACL reconstruction with BTB autografts may restore knee function and stability.

Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing

Tendon-bone interface injuries pose a significant challenge in tissue regeneration,necessitating innovative approaches.Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries.In this study,we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions(Mg^(2+)).We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles(Mg-PC)through a self-assembly process and integrated them into a two-component hydrogel.The hydrogel was composed of dopamine-modified hyaluronic acid(Dop-HA)and F127.To ensure controlled release and mitigate the“burst release”effect of Mg^(2+),we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel.This crosslinking strategy extended the release window of Mg^(2+)concentrations for up to 56 days.The resulting hydrogel(Mg-PC@Dop-HA/F127)exhibited favorable properties,including injectability,thermosensitivity and shape adaptability,making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites.Furthermore,the hydrogel sustained the release of Mg^(2+)and Procyanidins,which attracted mesenchymal stem and progenitor cells,alleviated inflammation,and promoted macrophage polarization towards the M2 phenotype.Additionally,it enhanced collagen synthesis and mineralization,facilitating the repair of the tendon-bone interface.By incorporating multilevel metal phenolic networks(MPN)to control ion release,these hybridized hydrogels can be customized for various biomedical applications.

Degradable magnesium alloy suture promotes fibrocartilaginous interface regeneration in a rat rotator cuff transosseous repair model

Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation,the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures.In the present work,degradable magnesium(Mg)alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4±0 absorbable suture as control.The shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4,8,and 12 weeks after operation.The Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to failure.Gross observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture groups.In the histological analysis,for Mg alloy suture groups,chondrocytes appear to proliferate at 4 weeks postoperatively,and the tendon-bone interface showed an orderly structural transition zone at 8 weeks postoperatively.The collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed,where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous enthesis.In vivo degradation of the magnesium alloy wire was completed within 12 weeks.The results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.

Canine ACL reconstruction with an injectable hydroxyapatite/collagen paste for accelerated healing of tendon-bone interface

Healing of an anterior cruciate ligament(ACL)autologous graft in a bone tunnel occurs through the formation of fibrovascular scar tissue,which is structurally and compositionally inferior to normal fibrocartilaginous insertion and thus may increase the reconstruction failure and the rate of failure recurrence.In this study,an injectable hydroxyapatite/type I collagen(HAp/Col I)paste was developed to construct a suitable local microenvironment to accelerate the healing of bone-tendon interface.Physicochemical characterization demonstrated that the HAp/Col I paste was injectable,uniform and stable.The in vitro cell culture illustrated that the paste could promote MC3T3-E1 cells proliferation and osteogenic expression.The results of a canine ACL reconstruction study showed that the reconstructive ACL had similar texture and color as the native ACL.The average width of the tunnel,total bone volume,bone volume/tissue volume and trabecular number acquired from micro-CT analysis suggested that the healing of tendon-bone interface in experimental group was better than that in control group.The biomechanical test showed the maximal loads in experimental group achieved approximately half of native ACL’s maximal load at 24 weeks.According to histological examination,Sharpey fibers could be observed as early as 12 weeks postoperatively while a typical four-layer transitional structure of insertion site was regenerated at 48 weeks in the experimental group.The injectable HAp/Col I paste provided a biomimetic scaffold and microenvironment for early cell attachment and proliferation,further osteogenic expression and extracellular matrix deposition,and in vivo structural and functional regeneration of the tendon-bone interface.

Nano-calcium silicate mineralized fish scale scaffolds for enhancing tendon-bone healing

Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery,however,this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity.Inspired by the high-performance exoskeleton of natural organisms,we set out to apply natural fish scale(FS)modified by calcium silicate nanoparticles(CS NPs)as a new biomaterial(CS-FS)to overcome the challenge.Benefit from its“Bouligand”microstructure,such FS-based scaffold maintained excellent tensile strength(125.05 MPa)and toughness(14.16 MJ/m^(3)),which are 1.93 and 2.72 times that of natural tendon respectively,allowing it to well meet the requirements for rotator cuff tendon repair.Additionally,CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction,(e.g.bone marrow mesenchymal stem cells(BMSCs),chondrocyte,and tendon stem/progenitor cells(TSPCs)).In both rat and rabbit rotator cuff tear(RCT)models,CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function,which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs.Therefore,natural fish scale-based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.

Biological approaches to the repair and regeneration of the rotator cuff tendon-bone enthesis:a literature review

Entheses are highly specialised organs connecting ligaments and tendons to bones,facilitating force transmission,and providing mechanical strengths to absorb forces encountered.Two types of entheses,fibrocartilaginous and fibrous,exist in interfaces.The gradual fibrocartilaginous type is in rotator cuff tendons and is more frequently injured due to the poor healing capacity that leads to loss of the original structural and biomechanical properties and is attributed to the high prevalence of retears.Fluctuating methodologies and outcomes of biological approaches are challenges to overcome for them to be routinely used in clinics.Therefore,stratifying the existing literature according to different categories(chronicity,extent of tear,and studied population)would effectively guide repair approaches.This literature review supports tissue engineering approaches to promote rotator cuff enthesis healing employing cells,growth factors,and scaffolds period.Outcomes suggest its promising role in animal studies as well as some clinical trials and that combination therapies are more beneficial than individualized ones.It then highlights the importance of tailoring interventions according to the tear extent,chronicity,and the population being treated.Contributing factors such as loading,deficiencies,and lifestyle habits should also be taken into consideration.Optimum results can be achieved if biological,mechanical,and environmental factors are approached.It is challenging to determine whether variations are due to the interventions themselves,the animal models,loading regimen,materials,or tear mechanisms.Future research should focus on tailoring interventions for different categories to formulate protocols,which would best guide regenerative medicine decision making.

Bone marrow mesenchymal stem cell-derived exosomal microRNAs target PI3K/Akt signaling pathway to promote the activation of fibroblasts

BACKGROUND Fibroblast plays a major role in tendon-bone healing.Exosomes derived from bone marrow mesenchymal stem cells(BMSCs)can activate fibroblasts and promote tendon-bone healing via the contained microRNAs(miRNAs).However,the underlying mechanism is not comprehensively understood.Herein,this study aimed to identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets,and to verify their effects as well as mechanisms on fibroblasts.AIM To identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets and verify their effects as well as mechanisms on fibroblasts.METHODS BMSC-derived exosomal miRNAs data(GSE71241,GSE153752,and GSE85341)were downloaded from the Gene Expression Omnibus(GEO)database.The candidate miRNAs were obtained by the intersection of three data sets.TargetScan was used to predict potential target genes for the candidate miRNAs.Functional and pathway analyses were conducted using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases,respectively,by processing data with the Metascape.Highly interconnected genes in the protein-protein interaction(PPI)network were analyzed using Cytoscape software.Bromodeoxyuridine,wound healing assay,collagen contraction assay and the expression of COL I andα-smooth muscle actin positive were applied to investigate the cell proliferation,migration and collagen synthesis.Quantitative real-time reverse transcription polymerase chain reaction was applied to determine the cell fibroblastic,tenogenic,and chondrogenic potential.RESULTS Bioinformatics analyses found two BMSC-derived exosomal miRNAs,has-miR-144-3p and hasmiR-23b-3p,were overlapped in three GSE datasets.PPI network analysis and functional enrichment analyses in the GO and KEGG databases indicated that both miRNAs regulated the PI3K/Akt signaling pathway by targeting phosphatase and tensin homolog(PTEN).In vitro experiments confirmed that miR-144-3p and miR-23b-3p stimulated proliferation,migration and collagen synthesis of NIH3T3 fibroblasts.Interfering with PTEN affected the phosphorylation of Akt and thus activated fibroblasts.Inhibition of PTEN also promoted the fibroblastic,tenogenic,and chondrogenic potential of NIH3T3 fibroblasts.CONCLUSION BMSC-derived exosomes promote fibroblast activation possibly through the PTEN and PI3K/Akt signaling pathways,which may serve as potential targets to further promote tendon-bone healing.

自体髌骨膜-髌韧带-骨瓣重建踝外侧韧带的应用解剖

目的为自体髌骨膜-髌韧带-骨瓣重建踝关节外侧韧带提供解剖学基础。方法在6侧经防腐固定的成人下肢标本及6侧新鲜标本上观测踝关节外侧韧带起止点及走行径路、髌韧带的解剖形态与起止点,在新鲜标本上摹拟重建手术。结果髌韧带位置恒定,解剖层次表浅,切取方便,髌骨膜-髌韧带-骨瓣的髌韧带长度(4.1±0.4)cm,距腓前韧带长度(2.4±0.5)cm,跟腓韧带长度(3.1±0.4)cm。结论 (1)髌骨膜-髌韧带-骨瓣的髌韧带具有足够的长度,可形成移植供体(;2)髌骨膜-髌韧带-骨瓣复合体两端分别与骨及软骨创面固定,容易成活和恢复功能(;3)采用自体髌骨膜-髌韧带-骨瓣重建踝外侧韧带具有可行性。

Anterior cruciate ligament reconstruction best practice: A review of graft choice

There is much literature about differing grafts used in anterior cruciate ligament(ACL) reconstruction. Much of this is of poor quality and of a low evidence base. We review and summarise the literature looking at the four main classes of grafts used in ACL reconstruction; bone-patella tendon-bone, hamstrings, allograft and synthetic grafts. Each graft has the evidence for its use reviewed and then compared, where possible, to the others. We conclude that although there is no clear "best" graft, there are clear differences between the differing graft choices. Surgeon's need to be aware of the evidence behind these differences, in order to have appropriate discussions with their patients, so as to come to an informed choice of graft type to best suit each individual patient and their requirements.

Low-intensity pulsed ultrasound therapy: a potential strategy to stimulate tendon-bone junction healing

Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successfulanterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. En-hancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return topre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B)healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis,stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-Bhealing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulateT-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities inthe near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular andmolecular levels, describe studies in animal models, and provide a future direction for research.

Combination of graphene oxide and platelet-rich plasma improves tendon-bone healing in a rabbit model of supraspinatus tendon reconstruction

The treatment of rotator cuff tear is one of the major challenges for orthopedic surgeons.The key to treatment is the reconstruction of the tendon-bone interface(TBI).Autologous platelet-rich plasma(PRP)is used as a therapeutic agent to accelerate the healing of tendons,as it contains a variety of growth factors and is easy to prepare.Graphene oxide(GO)is known to improve the physical properties of biomaterials and promote tissue repair.In this study,PRP gels containing various concentrations of GO were prepared to promote TBI healing and supraspinatus tendon reconstruction in a rabbit model.The incorporation of GO improved the ultrastructure and mechanical properties of the PRP gels.The gels containing 0.5 mg/ml GO(0.5 GO/PRP)continuously released transforming growth factor-b1(TGF-b1)and platelet-derived growth factor(PDGF)-AB,and the released TGF-b1 and PDGF-AB were still at high concentrations,1063.451 pg/ml and814.217 pg/ml,respectively,on the 14th day.In vitro assays showed that the 0.5 GO/PRP gels had good biocompatibility and promoted bone marrow mesenchymal stem cells proliferation and osteogenic and chondrogenic differentiation.After 12 weeks of implantation,the magnetic resonance imaging,microcomputed tomography and histological results indicated that the newly regenerated tendons in the 0.5 GO/PRP group had a similar structure to natural tendons.Moreover,the biomechanical results showed that the newly formed tendons in the 0.5 GO/PRP group had better biomechanical properties compared to those in the other groups,and had more stable TBI tissue.Therefore,the combination of PRP and GO has the potential to be a powerful advancement in the treatment of rotator cuff injuries.

Discussing tuina for atlantoaxial subluxation in adults based on the theory of‘tendon-bone balance’

According to Chinese medicine,the atlantoaxial joint is a composite joint composed of tendons and bones,and the stability of the joint depends on the‘tendon-bone balance’involving tendons,ligaments,atlas and axis.Multiple causes of‘tendon off-position,joint subluxation’will lead to joint‘tendon-bone imbalance’,which will evolve into atlantoaxial subluxation(AAS),endangering human health.Chinese therapeutic massage(tuina)is a very effective treatment for AAS in adults,but conventional manipulations are prone to ineffectiveness or accidents due to neglect of the causal relationship of the‘tendon-bone imbalance’and inappropriate manipulations.Compared with conventional manipulations,the rational choice of modified manipulations under the guidance of‘tendon-bone balance’theory is more effective and less risky,and more worthy of clinical promotion.From the‘tendon-bone balance’theory,we considered the shortcomings of conventional manipulations,and introduced several modified manipulations that have their own strengths in‘tendon smoothing’and‘bone setting’,in order to provide new ideas for treatment of AAS in adults.

Multi-functionalized nanofibers with reactive oxygen species scavenging capability and fibrocartilage inductivity for tendon-bone integration

The presence of excessive reactive oxygen species(ROS)after injuries to the enthesis could lead to cellular oxidative damage,high inflammatory response,chronic inflammation,and limited fibrochondral inductivity,making tissue repair and functional recovery difficult.Here,a multifunctional silk fibroin nanofiber modified with polydopamine and kartogenin was designed and fabricated to not only effectively reduce inflammation by scavenging ROS in the early stage of the enthesis healing but also enhance fibrocartilage formation with fibrochondrogenic induction in the later stages.The in vitro results confirmed the antioxidant capability and the fibrochondral inductivity of the functionalized nanofibers.In vivo studies showed that the multifunctional nanofiber can significantly improve the integration of tendon-bone and accelerate the regeneration of interface tissue,resulting in an excellent biomechanical property.Thus,the incorporation of antioxidant and bio-active molecules into extracellular matrix-like biomaterials in interface tissue engineering provides an integrative approach that facilitates damaged tissue regeneration and functional recovery,thereby improving the clinical outcome of the engineered tissue.

High-purity magnesium screws modulate macrophage polarization during the tendon–bone healing process in the anterior cruciate ligament reconstruction rabbit model

Magnesium(Mg)screws perform clinical potential in anterior cruciate ligament(ACL)reconstruction,and promote fibrocartilaginous entheses regeneration at the femoral entrance.We aim to prove that high-purity Magnesium(HP Mg)screws modulate macrophage polarization in fibrocartilage interface regeneration both in vitro and in vivo.HP Mg extracts performed good cytocompatibility and significantly promoted M2 macrophage polarization in the flow cytometry and ELISA assays.M2 macrophages stimulated fibrochondrocyte differentiation of cocultured hBMSCs,and HP Mg extracts had synergistic effect on the process.Then we applied HP Mg screws,with Ti screws as control,in the ACL reconstruction rabbit model.In the histological and immunofluorescence analysis,HP Mg screws inhibited M1 polarization at 2 weeks and highly promoted M2 polarization at 2 and 4 weeks at the tendon–bone interface.Furthermore,regeneration of fibrocartilaginous entheses,rather than the fibrovascular scar interface,was detected in the HP Mg group at 12 weeks.For further mechanism study via RNA-seq detection and WB assays,we found that AKT1 was highly activated in M2 polarization,and HP Mg could stimulate AKT1 expression,rather than AKT2,in the early phase of tendon–bone healing.Our study elucidated macrophage polarization during tendon–bone healing process and emphasized HP Mg on M2 polarization and fibrocartilage interface regeneration via the selective activation of AKT1 and PI3K/AKT pathway.