Native Meniscus Research Articles

Synergistic hydration lubrication of polyurethane meniscus based on zwitterionic structures and hyaluronic acid

In this study, polyurethanes with graded sulfobetaine content (PU-SBs) were employed to resolve the high friction of artificial menisci. Under the simulated gait of knee joints, the coefficient of friction of PU-SB60 in hyaluronic acid (HA) aqueous solution was similar to that of the native meniscus. Importantly, this phenomenon was caused by synergistic hydration lubrication based on sulfobetaine groups and HA, that a thicker and stronger hydration layer was preferred to form quickly on the surfaces of HA-adsorbed PU-SB60 and was harder to be destroyed by the friction force. Furthermore, PU-SB60 exhibited both excellent modulus and long-term low cytotoxicity. Therefore, PU-SB60 has the potential to be applied for artificial menisci due to its overall performance.

Knee meniscus regeneration using autogenous injection of uncultured adipose tissue-derived regenerative cells.

IntroductionThe low healing potential of mature menisci necessitates traditional surgical removal (meniscectomy) to eliminate acute or chronic degenerative tears. However, removal of meniscal tissue is main factor causing osteoarthritis. Adipose tissue-derived regenerative cells (ADRCs), a heterogeneous cell population that includes multipotent adipose-derived stem cells and other progenitor cells, were easily isolated in large amounts from autologous adipose tissue, and same-day processing without culture or expansion was possible. This study investigated the regenerative potential of autologous ADRCs for use in meniscus defects.MethodsIn 10- to 12-week-old male SD rat partial meniscectomy model, an atelocollagen sponge scaffold without or with ADRCs (5.0 × 105 cells) was injected into each meniscus defect. Reconstructed menisci were subjected to histologic, and dynamic mechanical analyses.ResultsAfter 12 weeks, areas of regenerated meniscal tissue in the atelocollagen sponge scaffold in rats with ADRCs (64.54 ± 0.52%, P < 0.05, n = 10) were larger than in those without injection (57.96 ± 0.45%). ADRCs were shown capable of differentiating chondrocyte-like cells and meniscal tissue components such as type II collagen. Higher elastic moduli and lower fluid permeability of regenerated meniscal tissue demonstrated a favorable structure-function relationship required for native menisci, most likely in association with micron-scale porosity, with the lowest level for tissue integrity possibly reproducible.ConclusionsThis is the first report of meniscus regeneration induced by injection of ADRCs. The results indicate that ADRCs will be useful in future clinical cell-based therapy strategies, including as a cell source for reconstruction of damaged knee menisci.

An anatomically shaped medial meniscus prosthesis is able to partially restore the contact mechanics of the meniscectomized knee joint

PurposeThe aim of this study was to determine whether a flexible medial meniscus prosthesis is more capable of sharing loads with the direct tibiofemoral cartilage contact than the stiffer first-generation prosthesis. Additionally, the effect of the prosthesis on the tibial pressure distribution after total meniscectomy was investigated.MethodsIn an artificial knee joint, the relative amounts of load transferred through both meniscus prostheses and the direct tibiofemoral contact were assessed with pressure-sensitive sensors.Additionally, six cadaveric knee joints were loaded in a physiological environment. Tibial contact pressures were measured with an intact native meniscus, after total meniscectomy and after implantation of the second-generation meniscus prosthesis.ResultsWhereas the first generation of the meniscus prosthesis transferred virtually all the load from femur to tibia, the second-generation prosthesis allowed for load sharing with the direct tibiofemoral contact.No differences in load sharing were found between the native meniscus and the second-generation meniscus prosthesis. The prosthesis decreased peak and mean pressures on the medial tibial cartilage compared to meniscectomy. No significant differences in pressure were found between the native meniscus and the meniscus prosthesis.ConclusionsThe second-generation meniscus prosthesis presented in this study can share loads with the direct tibiofemoral contact, a characteristic that the first-generation prosthesis did not have.The flexible meniscus prosthesis significantly reduces the contact pressures on the medial tibial plateau after total meniscectomy. Although the biomechanical performance of the native meniscus could not be reproduced completely, the meniscus prosthesis may have the potential to relieve post-meniscectomy pain symptoms.

All-Soft Tissue Meniscus Allograft Transplantation: Indications, Techniques, and Results

Background: Meniscus allograft transplantation (MAT) may be indicated for young patients with joint line pain following subtotal or total meniscectomy. Several different approaches for performing MAT have been described in the literature and are influenced by appropriate patient selection, graft-sizing, and soft-tissue fixation techniques. Clinical studies demonstrate favorable results regarding pain relief and knee function in young patients undergoing MAT, making it a viable option for the treatment of postmeniscectomy syndrome. Indications: Meniscus allograft transplantation is indicated for symptomatic patients following subtotal or total meniscectomy. Selection criteria include patient age below 40 to 45 years, body mass index below 35, chondral changes of grade 2 or less, anatomic or correctable joint alignment, and normal or correctable knee stability. Technique Description: A standard arthroscopy is performed to confirm the indication for MAT, followed by debridement of the meniscus remnant up to the meniscus-capsular junction. The meniscus horns are prepared using a single No. 5 suture, while 4 to 5 No. 2 sutures are passed through the posterior body. The anterior and posterior root tunnels are drilled, and the meniscus is inserted through a posterior vertical arthrotomy using suture passers transmitted via the bone tunnels. The allograft is manipulated into proper position with a probe and the application of axial traction on the posterior root suture. At this point, sutures attached to the posterior horn are passed to the posterior capsule and 6 to 8 inside-out sutures are used to stabilize and fixate the midbody and anterior portion of the allograft. Results: Several clinical studies report good outcomes following MAT with a mean survival rate of approximately 70% at 10-year follow-up and 60% at 15 years. Additionally, some evidence is currently available regarding the long-term chondroprotective effect of MAT. Description/Conclusion: All-soft tissue meniscus allograft transplantation is a feasible approach for substitution of the damaged native meniscus and maintenance of tibiofemoral contact mechanics. Consequently, MAT is an important procedure in the toolkit of knee surgeons providing treatment for young, symptomatic postmeniscectomy patients.

Decellularized small intestine submucosa device for temporomandibular joint meniscus repair: Acute timepoint safety study.

Temporomandibular joint (TMJ) Meniscus removal is an option for the patient to regain full range of motion if the disc is irreversibly damaged or unable to be reduced. However, this procedure leaves the joint vulnerable to condylar remodeling and degeneration. We have shown that extracellular matrix (ECM) scaffolds remodel into a tissue with near native TMJ meniscus in previous studies. The next step towards clinical translation is to manufacture the ECM scaffold as a device under good manufacturing practices (GMP) and test it in a pre-clinical animal study under good laboratory practices (GLP). The primary objective of this study was to evaluate the in-vivo histopathological response to a Prototype GMP manufactured device made of decellularized porcine small intestinal submucosa (SIS), by observing for signs of surrounding tissue reaction to the device that are indicative of an adverse host response in comparison to an empty control at 21 days post-surgical implantation in a canine TMJ meniscus removal and implant model in a GLP setting. The conclusive findings were that the ECM device is safe for placement in the TMJ. After 21 days post implantation, histology of tissue surrounding the device and draining lymph nodes showed that the Prototype GMP device had no negative effects compared to the empty site (as evaluated by the board-certified veterinary pathologist). Furthermore, there was a lack of negative findings for clinical pathology (hematology and clinical chemistry), mortality, and body weight/weight change. Future studies will go to one year after implantation to show that the remodel device remains as a viable tissue with near native mechanical properties.

Optimizing artificial meniscus by mechanical stimulation of the chondrocyte-laden acellular meniscus using ad hoc bioreactor

BackgroundTissue engineering focuses on reconstructing the damaged meniscus by mimicking the native meniscus. The application of mechanical loading on chondrocyte-laden decellularized whole meniscus is providing the natural microenvironment. The goal of this study was to evaluate the effects of dynamic compression and shear load on chondrocyte-laden decellularized meniscus.Material and methodsThe fresh samples of rabbit menisci were decellularized, and the DNA removal was confirmed by histological assessments and DNA quantification. The biocompatibility, degradation and hydration rate of decellularized menisci were evaluated. The decellularized meniscus was injected at a density of 1 × 105 chondrocyte per scaffold and was subjected to 3 cycles of dynamic compression and shear stimuli (1 h of 5% strain, ± 25°shear at 1 Hz followed by 1 h rest) every other day for 2 weeks using an ad hoc bioreactor. Cytotoxicity, GAG content, ultrastructure, gene expression and mechanical properties were examined in dynamic and static condition and compared to decellularized and intact menisci.ResultsMechanical stimulation supported cell viability and increased glycosaminoglycan (GAG) accumulation. The expression of collagen-I (COL-I, 10.7-folds), COL-II (6.4-folds), aggrecan (AGG, 3.2-folds), and matrix metalloproteinase (MMP3, 2.3-folds) was upregulated compared to the static conditions. Furthermore, more aligned fibers and enhanced tensile strength were observed in the meniscus treated in dynamic condition with no sign of mineralization.ConclusionCompress and shear stimulation mimics the loads on the joint during walking and be able to improve cell function and ultrastructure of engineered tissue to recreate a functional artificial meniscus.

Mechanical and Microstructural Properties of Meniscus Roots Vary by Location

Background: Despite the growing awareness of the clinical significance of meniscus root tears, there are relatively limited biomechanical and microstructural data available on native meniscus roots that could improve our understanding of why they are injured and how to best treat them. Purpose/Hypothesis: The purpose of the study was to measure the material and microstructural properties of meniscus roots using mechanical testing and quantitative polarized light imaging. The hypothesis was that these properties vary by location (medial vs lateral, anterior vs posterior) and by specific root (anteromedial vs anterolateral, posteromedial vs posterolateral). Study Design: Descriptive laboratory study. Methods: Anterior and posterior meniscus roots of the medial and lateral meniscus were isolated from 22 cadavers (10 female, 12 male; mean ± SD age, 47.1 ± 5.1 years) and loaded in uniaxial tension. Quantitative polarized light imaging was used to measure collagen fiber organization and realignment under load. Samples were subjected to preconditioning, stress-relaxation, and a ramp to failure. Time-dependent relaxation behavior was quantified. Modulus values were computed in the toe and linear regions of the stress-strain curves. The degree of linear polarization (DoLP) and angle of polarization—measures of the strength and direction of collagen alignment, respectively—were calculated during the stress-relaxation test and at specific strain values throughout the ramp to failure (zero, transition, and linear strain). Results: Anterior roots had larger moduli than posterior roots in the toe (P = .007) and linear (P < .0001) regions and larger average DoLP values at all points of the ramp to failure (zero, P = .016; transition, P = .004; linear, P = .002). Posterior roots had larger values across all regions in terms of standard deviation angle of polarization (P < .001). Lateral roots had greater modulus values versus medial roots in the toe (P = .027) and linear (P = .014) regions. Across all strain points, posterolateral roots had smaller mean DoLP values than posteromedial roots. Conclusion: Posterior meniscus roots have smaller modulus values and more disorganized collagen alignment at all strain levels when compared with anterior roots. Posterolateral roots have lower strength of collagen alignment versus posteromedial roots. Clinical Relevance: These data findings may explain at least in part the relative paucity of anterior meniscus root tears and the predominance of traumatic posterolateral roots tears as compared with degenerative posteromedial root tears.

Meniscal Root Tears: A Decade of Research on their Relevant Anatomy, Biomechanics, Diagnosis, and Treatment.

A foundational knowledge of the anatomy and biomechanics of meniscal root tears is warranted for proper repair of meniscal root tears and for preventing some of their commonly described iatrogenic causes. Meniscal root tears are defined as either a radial tear occurring within one cm of the root attachment site of the meniscus or a complete bony or soft tissue avulsion of the root attachment altogether. Meniscal root tears disrupt the protective biomechanical function of the native meniscus. Biomechanical analyses of the current techniques for meniscal root repair highlight the importance of restoring menisci to their correct anatomic orientation, thereby restoring their biomechanical function. A comprehensive understanding of the clinical and radiographic presentations of these injuries is critical to preventing their underdiagnosis. The poor long-term outcomes associated with conservative treatment measures, namely, ipsilateral compartment osteoarthritis, warrants the surgical repair of meniscal root tears whenever possible. While excellent patient-reported outcomes exist for the various surgical repair techniques, adherence to stringent post-operative rehabilitation protocols is critical for patients to avoid damaging the integrity of a repaired root. This review will focus on current concepts pertaining to the anatomy, biomechanics, diagnosis, treatment, and postoperative rehabilitation for meniscal root tears.

The Cell-Material Interaction in the Replacement and Regeneration of the Meniscus: A Mini-Review

The meniscus is a part of the knee joint consisting of a medial and lateral component between the femoral condyles and the tibial plateau. Meniscal tears usually happen in younger and active people due to sports or daily activities. Some approaches are chosen for meniscus replacement and regeneration from the problems above, such as meniscal repair, meniscal allograft transplantation, gene therapy techniques, and tissue engineering techniques. Biomaterials and tissue engineering have a primary role in meniscus regeneration and replacement. The cell-material interactions are influenced by the biomaterials' design, structure, and composition to promote the growth o meniscus tissue. This study aims to give a brief review of the cell-material interaction in the replacement and regeneration process of the meniscus. Based on several studies, the use of growth factors in the meniscal regeneration and replacement could modulate and promote angiogenesis, differentiation, and cell migration beneficial in the repair process of the meniscus. Furthermore, combining the Mesenchymal Stem Cells and growth factors in healing the meniscal tears could be one of the best approaches to obtaining the new tissue resembling the meniscal tissue. The follow-up and long-term studies in meniscus regeneration and replacement are needed and recommended, especially implanting with good chondroprotective and long-term evaluation to obtain the best properties similar to the natural meniscus.

Prospective Application of Partially Digested Autologous Chondrocyte for Meniscus Tissue Engineering.

Background: Meniscus tissue engineering has yet to achieve clinical application because it requires chondrogenic induction and in vitro cell expansion. Contrarily, cartilage engineering from autologous chondrocytes has been successfully applied in one-stage surgery. If the natural chondrogenic potential of meniscus cells can be demonstrated, meniscus tissue engineering would have more value in clinical settings. Materials and Methods: In total, 10 menisci and pieces of cartilage were obtained during total knee replacements. The tissues were collected for cell isolation and expansion. Their chondrogenic properties were examined by immunohistofluorescence and gene expression analyses. Results: In native cartilage, immunofluorescence demonstrated the presence of collagen I, aggrecan, and traces of collagen I, whereas comparable staining was seen in the inner and middle meniscus. The presence of collagen I but the absence of collagen II and aggrecan were observed in the outer meniscus. In passage 2, chondrocytes showed the presence of collagen II and aggrecan, and the absence of vimentin. The vimentin and aggrecan staining were comparable in the inner and middle meniscus cells, whereas the outer cells showed only vimentin staining. In the gene expression analyses, the expressions of collagen II and aggrecan in the native chondrocyte and the inner and middle meniscus were higher than those of the cells from the outer meniscus, but they were not different in collagen I. In the passage 2 culture, chondrocytes had a higher expression of collagen II and aggrecan than the meniscus cells. Cells from the inner and middle areas had higher collagen II and aggrecan expression than those from the outer meniscus. Conclusion: Without chondrogenic induction, inner and middle meniscus cells possess a chondrogenic phenotype. Specifically, native meniscus cells exhibited more robust chondrogenic potential compared with those of the passage 2 monolayer culture.

3D Printed High‐Strength Supramolecular Polymer Hydrogel‐Cushioned Radially and Circumferentially Oriented Meniscus Substitute

AbstractDeveloping a meniscal replacement with reliable long‐term mechanical and functional support has faced a grand challenge due to difficulty in recapitulating the anisotropic microarchitecture and modulus. Herein, a high‐strength supramolecular polymer hydrogel‐cushioned biomimetic structured meniscus replacement is reported for the first time. The radially and circumferentially oriented poly(e‐caprolactone) (PCL) fiber framework is 3D printed to imitate collagen fibers in the native meniscus to provide circumferential tensile supports. Then, hydrogen bonding strengthened anti‐swelling poly(N‐acryloyl glycinamide) (PNAGA) hydrogel that replicates the function of proteoglycan in resisting axial compressive loads is infused into the 3D printed PCL framework, thus fulfilling a durable energy absorbing and cushion function, which far outperforms the performance of conventional polyacrylamide hydrogel. The PNAGA‐cushioned PCL construct can achieve Young's moduli of 20.15 ± 1.37 MPa in the circumferential direction and 10.43 ± 1.54 MPa in the radial direction, a compressive modulus of 1.11 ± 0.14 MPa as well as a tearing energy of 17.00 ± 2.07 kJ m−2. This 3D printed PCL‐PNAGA meniscus scaffold is implanted into rabbit knee joints for 12 weeks and in vivo outcome demonstrates the structural stability and efficient protection against wearing of the cartilage, meanwhile ameliorating the development of osteoarthritis.

Meniscal transplantation and regeneration using functionalized polyurethane bionic scaffold and digital light processing 3D printing

Owing to the limited healing ability, the repair of meniscal injury and prevention of secondary osteoarthritis pose considerable challenges for clinicians and researchers. While tissue engineering technology is a promising method, many difficulties, including the construction of the meniscus scaffold with appropriate mechanical properties and its functionalization to promote the regeneration of meniscus tissue, remain to be addressed. In this study, a novel structurally and functionally optimized tissue engineering meniscus scaffold with mechanical properties and spatial structure similar to those of a natural meniscus is prepared using digital light processing 3D printing technology. Kartogenin-loaded polyurethane scaffolds with a specific structure designed using finite element analysis are printed, and their surface is modified using polydopamine. The optimized scaffolds exhibit superior performance in promoting meniscus regeneration, protecting articular cartilage, and mitigating the development of osteoarthritis. Moreover, this study addresses challenges posed by polyurethane, which is found in most widely used commercial meniscus grafts, including unsatisfactory biocompatibility with stem cells and unavailability of a fine 3D structure. Although further research in preclinical applications is required, the results of this study in terms of a next-generation clinical meniscus biomaterial repair strategy are promising.

Biomechanical Comparison of Meniscal Allograft Root Fixation Techniques: Anterograde Interference Bone Plug Fixation Yields Favorable Results Compared to Transosseous Suture Fixation Alone

PurposeTo compare the biomechanical properties of 2 different fixation techniques (interference bone plug fixation vs transosseous suture fixation) of the posterior horn of the medial meniscus using a porcine model.MethodsTwenty-six matched pairs of fresh-frozen juvenile domestic porcine knees were used in this study. Specimens were randomly distributed among 3 groups: (1) native meniscus groups, (2) interference fixation, and (3) transosseous suture fixation. In each group, the posterior segments of the tested medial menisci were gripped with the freeze clamps and fixed to the tensile testing machine. Samples were preconditioned, followed by cyclic tension-relaxation for 1000 cycles between 10 and 30 N at 0.5 Hz and finally pulled to failure at a rate of 0.55 mm/s. The cyclic elongation, stiffness to failure, mode, and ultimate load to failure were recorded.ResultsThere was no significant difference in ultimate load to failure between the interference fixation (169.71 ± 71.98 N) and transosseous suture fixation (222.73 ± 72.40 N) groups (P = .118), both were significantly less than that of the native meniscus (405.46 ± 95.62) (P < .001). Interference fixation displayed cyclic elongation (1.04 ± 0.71 mm) and stiffness (69.10 ± 25.8 N/mm) that were not significantly different from the native meniscus tissue (0.78 ± 0.53 mm and 83.1 ±26.28 N/mm) (P = .359 and P = .224), in comparison to transosseous suture fixation, which did show increased cyclic elongation (1.85 ± 1.44 mm) (P = .047) and decreased stiffness (34.72 ± 10.2 N/mm) (P < .001).ConclusionInterference fixation of the posterior horn of the medial meniscus has superior cyclic elongation and stiffness when compared to transosseous suture fixation. Interference fixation and the native meniscus model have a similar stiffness and cyclic elongation.Clinical RelevanceThe significance of our study is that using interference fixation for meniscal allograft transplantation has the potential to reduce short term surgical failures as well as long term complication rates.

Technique for Arthroscopic Transtibial Medial Meniscus Posterior Root Repair

Background: Medial meniscus posterior root tears (MMPRT) can lead to significant pain, functional limitations, and osteoarthritis (OA). Biomechanically, MMPRT has been shown to be equivalent to total meniscectomy in terms of peak contact pressure in the medial compartment. Transtibial repair of a meniscus root tear has also been shown to restore hoop stresses and reduced peak contact pressure to the normal intact state. Clinically, root repair was shown to reduce rates of OA progression and need for total knee arthroplasty when compared with nonoperative treatment or partial meniscectomy for MMPRT. Indications: Medial meniscus posterior root repair is indicated in patients with a symptomatic MMPRT who are appropriate surgical candidates: age ≤65 years, body mass index ≤40 kg/m2, &lt;5° varus alignment, no more than Kellgren-Lawrence grade 2 changes, and willing and able to undergo the demanding postoperative rehabilitation program. Technique Description: This surgical technique video demonstrates our preferred technique for arthroscopic transtibial medial meniscus posterior root repair using a case example in a commonly encountered patient. The repair is completed using a 3 simple suture triangle configuration with 2 tibial tunnels to create a broad footprint for healing. Results: There are a number of case series and comparative studies published with good clinical outcomes using similar transtibial medial meniscus posterior root repair techniques. In short-term follow-up of 18 patients at a mean of 10.5 months post-operatively, we have demonstrated improvements in pain and functional status with a 16.7% clinical failure rate and 11% rate of conversion to arthroplasty. Discussion: In this surgical technique video, we review the anatomy of the native medial meniscus posterior root and the biomechanical and clinical consequences of a MMPRT. We highlight important technique pearls and pitfalls to avoid failures and complications during the surgical demonstration. Finally, we review postoperative rehabilitation guidelines and clinical outcomes within the existing literature. In patients with MMPRT, transtibial repair provides a safe and reliable technique to achieve healing of the medial meniscus posterior root and return patients to full activities with reduced risk of OA progression.

Effect of Silk Fibroin Content on Physical and Mechanical Properties of Electrospun Poly(lactic acid)/Silk Fibroin Nanofibers for Meniscus Tissue Engineering Scaffold

This study aims to produce composite nanofibers from polylactic acid (PLA) and silk fibroin (SF) with mechanical properties similar to that of a native meniscus. SF is a natural protein, well known for its good biocompatibility and biodegradability but it has poor mechanical properties compared to synthetic polymers. SF contains proteins which can promote cell adhesion and cell proliferation required for a tissue engineering scaffold. PLA is a popular material that is widely used in tissue engineering. It provides high mechanical properties but lacks bioactivity and cell affinity. Thus, a PLA/SF composite scaffold can improve these drawbacks. In this study, PLA/SF nanofibers were fabricated using an electrospinning process at various PLA and SF ratios (PLA: SF 100:0, 75:25, 50:50, and 25:75). The SF content in the emulsion dominated the fiber diameter, fiber arrangement and processibility of nanofibrous scaffold. With increasing SF content, the %elongation at break of PLA/SF scaffold increased but Young’s modulus decreased. The wettability of electrospun PLA was increased with an increase in SF content.

Regional-specific meniscal extracellular matrix hydrogels and their effects on cell–matrix interactions of fibrochondrocytes

Decellularized meniscal extracellular matrix (ECM) material holds great potential for meniscus repair and regeneration. Particularly, injectable ECM hydrogel is highly desirable for the minimally invasive treatment of irregularly shaped defects. Although regional-specific variations of the meniscus are well documented, no ECM hydrogel has been reported to simulate zonally specific microenvironments of the native meniscus. To fill the gap, different (outer, middle, and inner) zones of porcine menisci were separately decellularized. Then the regionally decellularized meniscal ECMs were solubilized by pepsin digestion, neutralized, and then form injectable hydrogels. The hydrogels were characterized in gelation behaviors and mechanical properties and seeded with bovine fibrochondrocytes to evaluate the regionally biochemical effects on the cell–matrix interactions. Our results showed that the decellularized inner meniscal ECM (IM) contained the greatest glycosaminoglycan (GAG) content and the least collagen content compared with the decellularized outer meniscal ECM (OM) and middle meniscal ECM (MM). The IM hydrogel showed lower compressive strength than the OM hydrogel. When encapsulated with fibrochondrocytes, the IM hydrogel accumulated more GAG, contracted to a greater extent and reached higher compressive strength than that of the OM hydrogel at 28 days. Our findings demonstrate that the regionally specific meniscal ECMs present biochemical variation and show various effects on the cell behaviors, thus providing information on how meniscal ECM hydrogels may be utilized to reconstruct the microenvironments of the native meniscus.

A 3D Bioprinted Human Meniscus Shape Enriched with Mesenchymal Cells

Background and objectives: Regenerative medicine, with its massive development over the years, has the potential to solve some of the most problematic medical issues, such as functional organ transplantation. The aim of this study was to create a human meniscal shape 3D-printed enriched with human adipose-derived mesenchymal cells. Materials and Methods: Human infrapatellar fat pad was harvested, and mesenchymal cells were isolated. The mesenchymal stem cells were differentiated to the chondrocite lineage and a hydrogel (a nanofibrillar cellulose, sodium alginate, D-mannitol, and Hepes buffer solution combination) cell mixture was bioprinted to create three human-size meniscus structures. The obtained structures were evaluated regarding the cell viability, appropriate size in relation to a native meniscus, and some mechanical characteristics. Results: The human meniscal shape created respected the anatomic characteristic of a native structure. Cell viability of approximately 97% and extracellular matrix formation after the printing process were observed. The mean maximum force for the meniscus with mesenchymal cells was 6.5 N (+/−0.5 N) compared to the mean maximum force for the native meniscus of 10.32 N (+/−0.7 N), which is statistically relevant (p &lt; 0.01). Conclusion: This paper presents the potential of bioprinting viable cell structures that could in the future present enough mechanical strength to replace a human organ, such as a meniscus. There are still limitations regarding the ink and the printing process, but we are confident that these problems will soon be solvable.

Three-Dimensional-Printed Scaffolds for Meniscus Tissue Engineering: Opportunity for the Future in the Orthopaedic World.

The meniscus is a critical component of a healthy knee joint. It is a complex and vital fibrocartilaginous tissue that maintains appropriate biomechanics. Injuries of the meniscus, particularly in the inner region, rarely heal and usually progress into structural breakdown, followed by meniscus deterioration and initiation of osteoarthritis. Conventional therapies range from conservative treatment, to partial meniscectomy and even meniscus transplantation. All the above have high long-term failure rates, with recurrence of symptoms. This communication presents a brief account of in vitro and in vivo studies and describes recent developments in the field of 3D-printed scaffolds for meniscus tissue engineering. Current research in meniscal tissue engineering tries to combine polymeric biomaterials, cell-based therapy, growth factors, and 3D-printed scaffolds to promote the healing of meniscal defects. Today, 3D-printing technology represents a big opportunity in the orthopaedic world to create more specific implants, enabling the rapid production of meniscal scaffolds and changing the way that orthopaedic surgeons plan procedures. In the future, 3D-printed meniscal scaffolds are likely to be available and will also be suitable substitutes in clinical applications, in an attempt to imitate the complexity of the native meniscus.

Precision 3D printed meniscus scaffolds to facilitate hMSCs proliferation and chondrogenic differentiation for tissue regeneration

BackgroundThe poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue.ResultsHerein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility.ConclusionsOverall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration.Graphical

The Long-term Chondroprotective Effect of Meniscal Allograft Transplant: A 10- to 14-Year Follow-up Study

Background: The long-term chondroprotective effect of meniscal allograft transplant (MAT) and its superiority over meniscectomy have rarely been reported. Hypothesis: MAT would reduce osteoarthritis (OA) progression when compared with the meniscus-deficient knee. Graft extrusion distance would strongly affect the chondroprotective effect of the MAT. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 17 knees receiving MAT were followed up as the MAT group. The MAT group was further divided into the nonextrusion subgroup (n = 9) and the extrusion subgroup (n = 8) according to 3-mm extrusion on the magnetic resonance imaging (MRI) coronal section. A further 26 consecutive patients receiving meniscectomy in the same period were followed up as the ME group. The healthy control group consisted of healthy contralateral legs chosen from the MAT and ME groups (n = 27). Joint space width (JSW) narrowing was measured on radiographs. Three-dimensional MRI with a T2 mapping sequence was used to quantitatively analyze cartilage degeneration and meniscal allograft extrusion in 5 directions (0°, 45°, 90°, 135°, and 180°). The cartilage degeneration index (CDI) was calculated according to the size and degree of the chondral lesions on MRI scans. The correlation between the CDI increase and the extrusion distance was analyzed. Results: The mean follow-up time was 11.3 years (range, 10-14 years). The MAT group had moderate superiority in chondral protection with less JSW narrowing (0.58 ± 0.66 mm) and CDI increase (1132 ± 1589) compared with the ME group (JSW narrowing: 1.26 ± 1.13 mm, P = .025; CDI increase: 2182 ± 1958, P = .079). The JSW narrowing (0.71 ± 0.80 mm; P = .186) and CDI increase (2004 ± 1965; P = .830) of the extrusion subgroup were close to those of the ME group, demonstrating that a 3-mm extrusion led to complete loss of the meniscal chondroprotective effect. The nonextrusion group had significantly less JSW narrowing (0.48 ± 0.48 mm; P = .042) and CDI increase (358 ± 249; P = .011) than the ME group. The JSW narrowing of the healthy control group was 0.22 ± 0.27 mm. The cartilage T2 values of the extrusion subgroup were similar to those of the ME group, with more OA features, whereas the T2 values of the nonextrusion subgroup were closer to those of the healthy control group. The extrusion distance in the 90° direction (P = .002) and the follow-up time (P = .019) significantly affected the CDI increase in the multivariate regression model. The average extrusion distance in the 45°, 90°, and 135° directions better predicted chondroprotection compared with the other individual directions. Conclusion: MAT had moderate advantages in chondroprotection compared with meniscectomy in the long term. Graft extrusion distance strongly affected the chondroprotective effect of MAT. The chondroprotective effect of the nonextruded meniscal allograft was close to that of the native meniscus, whereas the allografts with an extrusion >3 mm completely lost their function after meniscectomy.