Dong Jiang

Role of scaffold mean pore size in meniscus regeneration

UNLABELLED Recently, meniscus tissue engineering offers a promising management for meniscus regeneration. Although rarely reported, the microarchitectures of scaffolds can deeply influence the behaviors of endogenous or exogenous stem/progenitor cells and subsequent tissue formation in meniscus tissue engineering. Herein, a series of three-dimensional (3D) poly(ε-caprolactone) (PCL) scaffolds with three distinct mean pore sizes (i.e., 215, 320, and 515μm) were fabricated via fused deposition modeling. The scaffold with the mean pore size of 215μm significantly improved both the proliferation and extracellular matrix (ECM) production/deposition of mesenchymal stem cells compared to all other groups in vitro. Moreover, scaffolds with mean pore size of 215μm exhibited the greatest tensile and compressive moduli in all the acellular and cellular studies. In addition, the relatively better results of fibrocartilaginous tissue formation and chondroprotection were observed in the 215μm scaffold group after substituting the rabbit medial meniscectomy for 12weeks. Overall, the mean pore size of 3D-printed PCL scaffold could affect cell behavior, ECM production, biomechanics, and repair effect significantly. The PCL scaffold with mean pore size of 215μm presented superior results both in vitro and in vivo, which could be an alternative for meniscus tissue engineering. STATEMENT OF SIGNIFICANCE Meniscus tissue engineering provides a promising strategy for meniscus regeneration. In this regard, the microarchitectures (e.g., mean pore size) of scaffolds remarkably impact the behaviors of cells and subsequent tissue formation, which has been rarely reported. Herein, three three-dimensional poly(ε-caprolactone) scaffolds with different mean pore sizes (i.e., 215, 320, and 515μm) were fabricated via fused deposition modeling. The results suggested that the mean pore size significantly affected the behaviors of endogenous or exogenous stem/progenitor cells and subsequent tissue formation. This study furthers our understanding of the cell-scaffold interaction in meniscus tissue engineering, which provides unique insight into the design of meniscus scaffolds for future clinical application.

Comparative study on immediate versus delayed meniscus allograft transplantation: 4- to 6-year follow-up.

Background: Meniscus allograft transplantation (MAT) is generally used for patients who sustain symptoms after meniscectomy, which could be called delayed MAT. Meniscus allograft transplantation for patients immediately after meniscectomy has not been reported. Hypothesis: Compared with the conventional delayed MAT, immediate MAT might provide better clinical results and reduce joint degeneration. Study Design: Cohort study; Level of evidence, 3. Methods: The study was performed with 18 transplanted menisci (6 medial, 12 lateral) from 16 patients. Eight menisci were transplanted immediately after meniscectomy (IM group); 10 menisci, from patients who complained of knee symptoms at a mean time of 35 months (range, 9-92 months) after total meniscectomy, underwent delayed transplantation (DE group). Fourteen patients undergoing meniscectomy during the same period were included as controls (ME group). Degenerative changes in knee joints were evaluated by plain radiographs and magnetic resonance imaging (MRI). Allograft extrusion and relative percentage of extrusion were measured on MRI. Other outcome assessments included preoperative and postoperative International Knee Documentation Committee (IKDC), Tegner, and Lysholm scores; visual analog scale (VAS) for pain; and range of motion and isokinetic muscle strength evaluation. Results: The mean length of follow-up was 50.8 months (range, 44-62 months) for the IM group, 72.0 months (range, 44-94 months) for the DE group, and 54.3 months (range, 45-62 months) for the ME group. A statistically significant difference in favor of the IM and ME groups was found on the VAS (0.4 [IM group] vs 1.1 [ME group] vs 2.5 [DE group]) and muscle strength (P < .05). The mean IKDC score in the IM group was significantly higher than that in the DE group (93 [range, 85-99] vs 74 [range, 38-95], respectively; P < .05). The IM group showed significantly less preoperative to postoperative cartilage degeneration changes on radiographs and MRI when compared with the DE and ME groups (Kellgren-Lawrence score changes: 0.25 [IM group] vs 1.0 [DE group] vs 1.7 [ME group]; Yulish score changes: 0.25 [IM group] vs 1.0 [DE group] vs 1.1 [ME group]; P < .05). Extrusion of the allograft was observed in the body of the menisci in all patients. No significant difference was found in terms of the Lysholm score, Tegner score, joint narrowing, or meniscus extrusion (P > .05). Conclusion: Compared with delayed MAT, immediate MAT led to more satisfactory subjective results, less joint degeneration, and less muscle strength deficits. The short-term results of delayed meniscus transplantation were close to those of meniscectomy.

3D-Printed Poly(ε-caprolactone) Scaffold Augmented With Mesenchymal Stem Cells for Total Meniscal Substitution: A 12- and 24-Week Animal Study in a Rabbit Model

Background: Total meniscectomy leads to knee osteoarthritis in the long term. The poly(ε-caprolactone) (PCL) scaffold is a promising material for meniscal tissue regeneration, but cell-free scaffolds result in relatively poor tissue regeneration and lead to joint degeneration. Hypothesis: A novel, 3-dimensional (3D)–printed PCL scaffold augmented with mesenchymal stem cells (MSCs) would offer benefits in meniscal regeneration and cartilage protection. Study Design: Controlled laboratory study. Methods: PCL meniscal scaffolds were 3D printed and seeded with bone marrow–derived MSCs. Seventy-two New Zealand White rabbits were included and were divided into 4 groups: cell-seeded scaffold, cell-free scaffold, sham operation, and total meniscectomy alone. The regeneration of the implanted tissue and the degeneration of articular cartilage were assessed by gross and microscopic (histological and scanning electron microscope) analysis at 12 and 24 weeks postoperatively. The mechanical properties of implants were also evaluated (tensile and compressive testing). Results: Compared with the cell-free group, the cell-seeded scaffold showed notably better gross appearance, with a shiny white color and a smooth surface. Fibrochondrocytes with extracellular collagen type I, II, and III and proteoglycans were found in both seeded and cell-free scaffold implants at 12 and 24 weeks, while the results were significantly better for the cell-seeded group at week 24. Furthermore, the cell-seeded group presented notably lower cartilage degeneration in both femur and tibia compared with the cell-free or meniscectomy group. Both the tensile and compressive properties of the implants in the cell-seeded group were significantly increased compared with those of the cell-free group. Conclusion: Seeding MSCs in the PCL scaffold increased its fibrocartilaginous tissue regeneration and mechanical strength, providing a functional replacement to protect articular cartilage from damage after total meniscectomy. Clinical Relevance: The study suggests the potential of the novel 3D PCL scaffold augmented with MSCs as an alternative meniscal substitution, although this approach requires further improvement before being used in clinical practice.

Meniscus transplantation using treated xenogeneic meniscal tissue: viability and chondroprotection study in rabbits.

PURPOSE This was a preliminary study performed in vivo to evaluate the viability and the chondroprotective effects of irradiated deep-frozen xenogeneic meniscal tissue as a novel substitute for meniscus transplantation. METHODS Medial meniscectomies were performed on the right knees of 48 New Zealand white rabbits. The inner one-third of pig meniscus was harvested and then irradiated and deeply frozen. The treated xenogeneic meniscal tissues were then transplanted to 24 right knees (Xeno group), whereas 24 other knees received meniscus allograft transplantations (Allo group). The left knees of the Xeno group and Allo group received meniscectomies (Meni group) and sham operations (Sham group), respectively. The rabbits were killed at weeks 6, 12, and 24 postoperatively. The newly formed structure of the implanted tissue and cartilage of the medial compartment of each group was assessed by gross and semiquantitative histologic analysis. RESULTS After 24 weeks, the implanted xenogeneic meniscal tissue completely healed to the synovium and formed meniscus-like tissue. The chondrocyte-like cell infiltrated into the tissue with extracellular matrix including type II collagen and proteoglycans. The Xeno group showed significantly less cartilage degeneration than that of the Meni group in the medial tibial plateau at week 24 (P < .05). No significant difference was found between the Xeno group and the Allo group except for the meniscus-covered regions at week 24. From week 12 to week 24, almost no advanced cartilage degeneration was found in weight-bearing regions of the medial tibial plateau of the Xeno group. CONCLUSIONS The treated xenogeneic meniscal tissue healed to the synovium with tissue regeneration and slowed down articular cartilage degeneration in the short-term. The chondroprotection of xenograft transplantation was similar to that of allograft transplantation. CLINICAL RELEVANCE The treated xenogeneic meniscal tissue showed the potential for viability and slowed cartilage degeneration, but more studies are required for application in humans in the future.

Repair of large full-thickness cartilage defect by activating endogenous peripheral blood stem cells and autologous periosteum flap transplantation combined with patellofemoral realignment.

Minimal-invasive procedure and one-step surgery offer autologous mesenchymal stem cells derived from peripheral blood (PB-MSCs) a promising prospective in the field of cartilage regeneration. We report a case of a 19-year-old male athlete of kickboxing with ICRS grade IV chondral lesions at the 60° region of lateral femoral trochlea, which was repaired by activating endogenous PB-MSCs plus autologous periosteum flap transplantation combined with correcting the patellofemoral malalignment. After a 7.5 year follow-up, the result showed that the patient returned to competitive kickboxing. Second-look under arthroscopy showed a smooth surface at 8 months postoperation. The IKDC 2000 subjective score, Lysholm score and Tegner score were 95, 98 and 9 respectively at the final follow up. CT and MRI evaluations showed a significant improvement compared with those of pre-operation.

Second-Look Arthroscopic Evaluation of Chondral Lesions After Isolated Anterior Cruciate Ligament Reconstruction Single- Versus Double-Bundle Reconstruction

Background: Double-bundle (DB) anterior cruciate ligament reconstruction (ACLR) has been reported to yield better joint stability than single-bundle (SB) reconstruction. Few studies have compared the 2 techniques with regard to postoperative articular cartilage changes. Hypothesis: Less cartilage damage should occur in the short term after DB ACLR than after SB ACLR. Study Design: Cohort study; Level of evidence, 2. Methods: The study included 52 patients (27 in the DB group and 25 in the SB group) with no chondral or meniscus injury at primary ACLR, as confirmed under arthroscopy. Four-strand and 6- to 8-strand hamstring autografts, respectively, were used for transtibial SB and 4-tunnel DB reconstruction. Each graft was fixed with an EndoButton bioabsorbable interference screw and a staple. Cartilage status at 6 identified regions was evaluated by second-look arthroscopy and the Outerbridge classification. Other assessments at final follow-up included International Knee Documentation Committee (IKDC) score, Tegner and Lysholm scores, side-to-side difference on KT-2000 arthrometer, and range of motion. Results: The mean time from reconstruction to second-look arthroscopy was 18.2 and 17.3 months for the DB and SB groups, respectively. Both groups had cartilage lesions at the patellofemoral joint (patella, 9 vs 13; trochlea, 5 vs 12) and the medial compartment (1 vs 2). Significantly less severe lesions were found in the DB group than in the SB group (mean grade, 0.33 vs 0.96; P < .05). No significant differences were found between the 2 groups in terms of cartilage status at other regions, IKDC score, Lysholm score, Tegner score, KT-2000 arthrometer anterior laxity, or range of motion. Conclusion: Chondral lesions were found postoperatively in both DB and SB ACLR groups with hamstring autograft. The DB ALCR led to less cartilage damage at the femoral trochlea at short-term follow-up.

Scaffolds drive meniscus tissue engineering

Meniscus injury is a common sports injury. The removal of the injured meniscus predisposes the development of osteoarthritis. Tissue engineering provides a promising approach for the treatment of meniscus injury. Over the past few decades, researchers have put a lot of effort in developing various kinds of scaffolds for preventing osteoarthritis and relieving clinical symptoms. The scaffolds for meniscus tissue engineering (MTE) can be categorized into four classes: hydrogels, three-dimensional (3D) porous polymeric scaffolds, extracellular matrix (ECM) macromolecule-based 3D matrices, and tissue-derived platforms. Although the expected efficacies in tissue integration and chondro-protective function have not yet emerged, several scaffolds have been exploited to provide new substitutes for native meniscus, suggesting their great potential in promoting tissue engineered meniscus (TEM). In the current review, we provide and discuss evidences on different scaffolds in order to make recommendations for the further development of MTE.

Double-Bundle Anterior Cruciate Ligament Reconstruction Using Bone–Patellar Tendon–Bone Allograft Technique and 2- to 5-Year Follow-up

Background: Nonanatomic transtibial single-bundle anterior cruciate ligament reconstruction (SB-ACLR) with a bone–patellar tendon–bone (BPTB) allograft has been used for a long time and has shown the same satisfactory clinical results as an autograft; however, it has not been reported if a double-bundle ACLR (DB-ACLR) could be performed with a BPTB allograft and achieve even better results. Hypothesis: The DB-ACLR with a BPTB allograft is technically feasible and will be superior to the SB technique in restoring better anterior and rotating stability. Study Design: Cohort study; Level of evidence, 2. Methods: The study was performed with 56 patients, and 52 (25 in the DB group and 27 in the SB group) of them were followed up at 2 to 5 years. With an irradiated deep-frozen BPTB allograft, a standard single-incision arthroscopic technique was used, and the graft was fixed with bioabsorbable interference screws on both the femoral and tibial sides. Outcome assessment at final follow-up included International Knee Documentation Committee (IKDC), Tegner, and Lysholm scores; side-to-side difference by conventional KT-2000 arthrometer; total anteroposterior (AP) laxity by the back-pushing KT-2000 arthrometer; pivot shift (0, +, ++); range of motion (ROM); and isokinetic muscle strength evaluation. Results: Mean follow-up was 47.3 ± 11.5 and 58.2 ± 6.6 months for the DB group and SB group, respectively. A statistically significant difference in favor of the DB group was found with the total AP laxity at 30° (P < .05). The overall incidence of pivot shift in the DB group (4% ++) was significantly lower than that in the SB group (26%: 19% + and 7% ++; P = .029). No significant differences were found between the 2 groups in terms of IKDC score, Lysholm score, Tegner score, conventional KT-2000 arthrometer anterior laxity, ROM, and muscle strength. Conclusion: A DB-ACLR with a BPTB allograft is feasible and achieved more satisfactory results than the transtibial SB technique in terms of total AP stability and rotational stability in spite of no significant differences among other clinical parameters.

Relationship Between Quadriceps Strength and Patellofemoral Joint Chondral Lesions After Anterior Cruciate Ligament Reconstruction

Background: The incidence of the patellofemoral joint chondral lesions after anterior cruciate ligament reconstruction (ACLR) is disturbingly high. Few studies have assessed the factors affecting patellofemoral joint chondral lesions postoperatively. Hypothesis: The recovery of quadriceps strength after ACLR could be associated with patellofemoral joint cartilage damage. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 88 patients who underwent arthroscopic anatomic double-bundle ACLR with hamstring autografts received second-look arthroscopy at the time of metal staple removal at an average of 24.1 months (range, 12-51 months) postoperatively. All patients underwent standardized isokinetic strength testing for bilateral quadriceps and hamstrings 1 to 2 days before second-look arthroscopy. The patients were divided into 2 groups: Patients in group 1 had a ≥20% deficit on the peak torque measures for quadriceps compared with that of the contralateral knee, whereas those in group 2 had a <20% deficit on peak torque. Cartilage status at the patellofemoral joint and tibiofemoral joint were evaluated by second-look arthroscopy and the Outerbridge classification. Other assessments included the International Knee Documentation Committee (IKDC) score, Tegner and Lysholm scores, side-to-side difference on KT-2000 arthrometer, and range of motion. Results: There were 42 patients included in group 1 and 46 patients in group 2. The mean postoperative quadriceps peak torque of the involved knee compared with the contralateral knee was 70% (range, 57%-80%) in group 1 and 95% (range, 81%-116%) in group 2. For all patients, a significant worsening was seen in the patellar and trochlear cartilage (P = .030 and <.001, respectively) but not at the medial or lateral tibiofemoral joint after ACLR. A significant worsening in the status of both patellar and trochlear cartilage was seen after ACLR in group 1 (P = .013 and =.011, respectively) and of trochlear cartilage in group 2 (P = .006). Significantly fewer severe chondral lesions of the patella were found in group 2 than in group 1 (proportion of patients whose cartilage grade worsened: 26% vs 48%, P < .05; difference in cartilage grade: 0.09 vs 0.62, P < .05). There was no significant difference for trochlear chondral worsening between the 2 groups. No significant differences were detected between the 2 groups in terms of hamstring strength; Lysholm, Tegner, and IKDC scores; KT-2000 arthrometer anterior laxity; or range of motion. Conclusion: Greater than 80% recovery of quadriceps strength after ACLR is associated with less severe patellar cartilage damage at short-term follow-up.

Potential of Centrifugal Seeding Method in Improving Cells Distribution and Proliferation on Demineralized Cancellous Bone Scaffolds for Tissue-Engineered Meniscus

Tissue-engineered meniscus offers a possible solution to the regeneration and replacement problem of meniscectomy. However, the nonuniform distribution and declined proliferation of seeded cells on scaffolds hinder the application of tissue-engineered meniscus as a new generation of meniscus graft. This study systematically investigated the performances of different seeding techniques by using the demineralized cancellous bone (DCB) as the scaffold. Static seeding, injection seeding, centrifugal seeding, and vacuum seeding methods were used to seed the meniscal fibrochondrocytes (MFCs) and mesenchymal stem cells (MSCs) to scaffolds. Cell-binding efficiency, survival rate, distribution ability, and long-term proliferation effects on scaffolds were quantitatively evaluated. Cell adhesion was compared via cell-binding kinetics. Cell viability and morphology were assessed by using fluorescence staining. Combined with the reconstructed three-dimensional image, the distribution of seeded cells was investigated. The Cell Counting Kit-8 assay and DNA assay were employed to assess cell proliferation. Cell-binding kinetics and cell survival of the MFCs were improved via centrifugal seeding compared to injection or vacuum seeding methods. Seeded MFCs by centrifugation showed a more homogeneous distribution throughout the scaffold than cells seeded by other methods. Moreover, the penetration depth in the scaffold of seeded MFCs by centrifugation was 300-500 μm, much higher than the value of 100-300 μm by the surface static and injection seeding. The long-term proliferation of the MFCs in the centrifugal group was also significantly higher than that in the other groups. The results of the MSCs were similar to those of the MFCs. The centrifugal seeding method could significantly improve MFCs or MSCs distribution and proliferation on the DCB scaffolds, thus providing a simple, cost-effective, and effective cell-seeding protocol for tissue-engineered meniscus.