Fibrocartilaginous Interface Research Articles

Degradation behavior of ZE21C magnesium alloy suture anchors and their effect on ligament-bone junction repair.

Current materials comprising suture anchors used to reconstruct ligament-bone junctions still have limitation in biocompatibility, degradability or mechanical properties. Magnesium alloys are potential bone implant materials, and Mg2+ has been shown to promote ligament-bone healing. Here, we used Mg-2 wt.% Zn-0.5wt.% Y-1wt.% Nd-0.5wt.% Zr (ZE21C) alloy and Ti6Al4V (TC4) alloy to prepare suture anchors to reconstruct the patellar ligament-tibia in SD rats. We studied the degradation behavior of the ZE21C suture anchor via in vitro and in vivo experiments and assessed its reparative effect on the ligament-bone junction. In vitro, the ZE21C suture anchor degraded gradually, and calcium and phosphorus products accumulated on its surface during degradation. In vivo, the ZE21C suture anchor could maintain its mechanical integrity within 12 weeks of implantation in rats. The tail of the ZE21C suture anchor in high stress concentration degraded rapidly during the early implantation stage (0-4weeks), while bone healing accelerated the degradation of the anchor head in the late implantation stage (4-12weeks). Radiological, histological, and biomechanical assays indicated that the ZE21C suture anchor promoted bone healing above the suture anchor and fibrocartilaginous interface regeneration in the ligament-bone junction, leading to better biomechanical strength than the TC4 group. Hence, this study provides a basis for further research on the clinical application of degradable magnesium alloy suture anchors.

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.

Kartogenin releasing decellularized umbilical cord Wharton's jelly scaffold promotes rotator cuff fibrocartilaginous interface regeneration

Fibrocartilaginous regeneration at the tendon-to-bone interface is a major challenge for rotator cuff tear repair. We fabricated a decellularized umbilical cord Wharton’s jelly (DUCWJ) scaffold by decellularization method and performed histological and proteomic analyses. We then synthesized a kartogenin-conjugated DUCWJ (DUCWJ-KGN) scaffold using an EDC/NHS catalyst. 1H NMR, Fluorescence staining, and FTIR confirmed that the carboxyl group of KGN was covalently coupled with the free amine groups in the Wharton’s jelly (WJ) matrix, and the in vitro release profiles of KGN from the DUCWJ-KGN scaffold showed sustained release for 6 weeks. Both the DUCWJ and DUCWJ-KGN scaffolds had excellent biocompatibility and biofunctionality, supporting cell attachment, migration, and proliferation, and DUCWJ-KGN scaffolds the KGN-loaded scaffold could induce higher chondrogenic markers expression. The DUCWJ-KGN scaffold could also promote fibrocartilaginous regeneration at the rotator cuff tendon-to-bone interface, which indicates that the DUCWJ-KGN scaffold is a promising enthesis to enhance fibrocartilaginous interface regeneration.

A rare case of Symptomatic Bipartite Patella in an adolescent male with review of literature and our experience

A bipartite patella results from the failure of the ossification centres to unite, resulting in a fibrocartilaginous union between the bipartite fragment and patella body. Fibrocartilaginous interface is present between the accessory and main patella. A bipartite patella is usually an incidental finding and can be hard to distinguish from a patella fracture. Here, we present a case of bipartite patella in 16 year old male and its further management.

3D cell-printing of tendon-bone interface using tissue-derived extracellular matrix bioinks for chronic rotator cuff repair

The tendon-bone interface (TBI) in rotator cuffs exhibits a structural and compositional gradient integrated through the fibrocartilaginous transition. Owing to restricted healing capacity, functional regeneration of the TBI is considered a great clinical challenge. Here, we establish a novel therapeutic platform based on 3D cell-printing and tissue-specific bioinks to achieve spatially-graded physiology for functional TBI regeneration. The 3D cell-printed TBI patch constructs are created via a spatial arrangement of cell-laden tendon and bone-specific bioinks in a graded manner, approximating a multi-tissue fibrocartilaginous interface. This TBI patch offers a cell favorable microenvironment, including high cell viability, proliferative capacity, and zonal-specific differentiation of encapsulated stem cells for TBI formation in vitro. Furthermore, in vivo application of spatially-graded TBI patches with stem cells demonstrates their regenerative potential, indicating that repair with 3D cell-printed TBI patch significantly accelerates and promotes TBI healing in a rat chronic tear model. Therefore, our findings propose a new therapeutic strategy for functional TBI regeneration using 3D cell-printing and tissue-specific decellularized extracellular matrix bioink-based approach.

Tough and tunable scaffold-hydrogel composite biomaterial for soft-to-hard musculoskeletal tissue interfaces.

Tendon inserts into bone via a fibrocartilaginous interface (enthesis) that reduces mechanical strain and tissue failure. Despite this toughening mechanism, tears occur because of acute (overload) or degradative (aging) processes. Surgically fixating torn tendon into bone results in the formation of a scar tissue interface with inferior biomechanical properties. Progress toward enthesis regeneration requires biomaterial approaches to protect cells from high levels of interfacial strain. We report an innovative tissue reinforcement strategy: a stratified scaffold containing osseous and tendinous tissue compartments attached through a continuous polyethylene glycol (PEG) hydrogel interface. Tuning the gelation kinetics of the hydrogel modulates integration with the flanking compartments and yields biomechanical performance advantages. Notably, the hydrogel interface reduces formation of strain concentrations between tissue compartments in conventional stratified biomaterials that can have deleterious biological effects. This design of mechanically robust stratified composite biomaterials may be appropriate for a broad range of tendon and ligament-to-bone insertions.

Sustained release of magnesium ions mediated by injectable self-healing adhesive hydrogel promotes fibrocartilaginous interface regeneration in the rabbit rotator cuff tear model

The fibrocartilaginous enthesis regeneration after rotator repair is still a major challenge. Although magnesium-based alloy orthopedic implant is effective to promote fibrocartilage formation at the tendon-bone interface in the anterior cruciate ligament reconstruction model, it was limited in the rotator cuff repair for its special anatomical structure. Herein, we developed a multifunctional self-healing magnesium ions-quaternized chitosan/Pluronic® F127 (Mg-QCS/PF) hydrogels to achieve in-situ and customized release of Mg2+, and demonstrated the sustained release of Mg2+ from the hydrogel to significantly promote the rotator cuff repair in the rabbit rotator cuff tear model. The obtained hydrogels showed excellent self-healing and anti-compressive performance. Additionally, the good injectability and adhesive properties of the hydrogels make it easier and stable to deliver Mg2+ at the tendon-bone interface with irregular shapes. The release of Mg2+ from Mg-QCS/PF hydrogels improved the adhesion, proliferation and migration of bone mesenchymal stem cells (BMSCs) and MC3T3 cells in vitro compared with QCS/PF without Mg2+. Furthermore, the composite hydrogels significantly enhanced the fibrocartilaginous interface regeneration in the rabbit rotator cuff tear model in terms of repaired tendon mature scores, fibrocartilage regeneration, collagen remodeling and biomechanical properties. This is the first study to demonstrate the positive effects of Mg2+ for the rotator cuff healing in the rabbit preclinical model, and the results indicate that the acellular injectable self-healing Mg-doped hydrogels are candidates to effectively promote in situ regeneration of rotator cuff.

The effectiveness of demineralized cortical bone matrix in a chronic rotator cuff tear model

The purpose of this study was to assess the effect of demineralized bone matrix (DBM) on rotator cuff tendon-bone healing. The hypothesis was that compared with a commercially available dermal matrix scaffold, DBM would result in a higher bone mineral density and regenerate a morphologically superior enthesis in a rat model of chronic rotator cuff degeneration. Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Three weeks later, tendon repair was carried out in animals randomized into 3 groups: group 1 animals were repaired with DBM (n = 6); group 2 received augmentation with the dermal scaffold (n = 6); and group 3 (controls) underwent nonaugmented tendon-bone repair (n = 6). Specimens were retrieved at 6 weeks postoperatively for histologic analysis and evaluation of bone mineral density. No failures of tendon-bone healing were noted throughout the study. All groups demonstrated closure of the tendon-bone gap with a fibrocartilaginous interface. Dermal collagen specimens exhibited a disorganized structure with significantly more abnormal collagen fiber arrangement and cellularity than in the DBM-based repairs. Nonaugmented repairs exhibited a significantly higher bone mineral density than in DBM and the dermal collagen specimens and were not significantly different from control limbs that were not operated on. The application of DBM to a rat model of chronic rotator cuff degeneration did not improve the composition of the healing enthesis compared with nonaugmented controls and a commercially available scaffold. However, perhaps the most important finding of this study was that the control group demonstrated a similar outcome to augmented repairs.

Aggregation of bovine anterior cruciate ligament fibroblasts or marrow stromal cells promotes aggrecan production

The development of a tissue-engineered alternative for current ligament grafts requires the creation of a fibrocartilaginous interface between the engineered ligament midsubstance and bone tissue. Therefore, the focus of this study was to examine the potential for cartilaginous extracellular matrix (ECM) formation by altering culture parameters for bovine anterior cruciate ligament (ACL) fibroblasts and marrow stromal cells (MSCs). Specifically, cells were cultured without chondrogenic media supplements on aggrecan-coated surfaces, tissue culture-treated control surfaces, and nonadhesive surfaces that promoted cell aggregation, and examined over 14 days. Aggrecan-coated surfaces promoted the aggregation of ACL fibroblasts and MSCs within 24 h after seeding. Aggrecan gene expression was significantly upregulated in cell aggregates, regardless of how cell clustering was induced, with as much as 10.9 ± 1.2-fold upregulation in ACL fibroblasts and 9.7 ± 1.1-fold in MSCs after 3 days, compared to control surfaces. Dimethylmethylene blue (DMMB) results and immunostaining verified the presence of aggrecan in ACL fibroblast and MSC aggregates throughout the culture period. Results indicate that ACL fibroblasts retained the ability to alter their gene expression and produce aggrecan, though MSCs, in general, had a more consistent response to aggregation. These findings support the use of aggregate-inducing materials to encourage production of aggrecan and suggest that altering the degree of clustering could produce a range of phenotypes from a single cell source. As such, this represents a first step which may inform future approaches to producing tissue-engineered ligament grafts.

Characterization of the structure–function relationship at the ligament-to-bone interface

Soft tissues such as ligaments and tendons integrate with bone through a fibrocartilaginous interface divided into noncalcified and calcified regions. This junction between distinct tissue types is frequently injured and not reestablished after surgical repair. Its regeneration is also limited by a lack of understanding of the structure-function relationship inherent at this complex interface. Therefore, focusing on the insertion site between the anterior cruciate ligament (ACL) and bone, the objectives of this study are: (i) to determine interface compressive mechanical properties, (ii) to characterize interface mineral presence and distribution, and (iii) to evaluate insertion site-dependent changes in mechanical properties and matrix mineral content. Interface mechanical properties were determined by coupling microcompression with optimized digital image correlation analysis, whereas mineral presence and distribution were characterized by energy dispersive x-ray analysis and backscattered scanning electron microscopy. Both region- and insertion-dependent changes in mechanical properties were found, with the calcified interface region exhibiting significantly greater compressive mechanical properties than the noncalcified region. Mineral presence was only detectable within the calcified interface and bone regions, and its distribution corresponds to region-dependent mechanical inhomogeneity. Additionally, the compressive mechanical properties of the tibial insertion were greater than those of the femoral. The interface structure-function relationship elucidated in this study provides critical insight for interface regeneration and the formation of complex tissue systems.

Augmentation of Tendon Healing in an Intraarticular Bone Tunnel with Use of a Bone Growth Factor

We hypothesized that an exogenous bone growth factor could augment healing of a tendon graft in a bone tunnel in a rabbit anterior cruciate ligament-reconstruction model. Seventy rabbits underwent bilateral anterior cruciate ligament reconstructions with a semitendinosus tendon graft. One limb received a collagen sponge carrier vehicle containing a mixture of bone-derived proteins while the contralateral limb was treated with either no sponge or a sponge without bone-derived proteins. The reconstruction was evaluated at 2, 4, or 8 weeks with histologic, biomechanical, and magnetic resonance imaging analysis. Histologic analysis demonstrated that specimens treated with bone-derived proteins had a more consistent, dense interface tissue and closer apposition of new bone to the graft, with occasional formation of a fibrocartilaginous interface, when compared with control specimens. The treated specimens had significantly higher load-to-failure rates than did control specimens. Treatment with bone-derived proteins resulted in an average increase in tensile strength of 65%. The treated specimens were stronger than control specimens at each time point, but the difference was greatest at 8 weeks. On the basis of signal characteristics and new bone formation, magnetic resonance imaging was useful for predicting which limb was treated, the site of failure, and the limbs with higher load-to-failure values. This study demonstrates the potential for augmenting tendon healing in an intraarticular bone tunnel using an osteoinductive growth factor.