Jay M. Patel

Successful Total Meniscus Reconstruction Using a Novel Fiber-Reinforced Scaffold: A 16- and 32-Week Study in an Ovine Model.

Background: Meniscus injuries in the United States result in an estimated 850,000 surgical procedures each year. Although meniscectomies are the most commonly performed orthopaedic surgery, little advancement has been made in meniscus replacement and regeneration, and there is currently no total meniscus replacement device approved by the Food and Drug Administration. Hypothesis: A novel fiber-reinforced meniscus scaffold can be used as a functional total meniscus replacement. Study Design: Controlled laboratory study. Methods: A tyrosine-derived, polymer fiber–reinforced collagen sponge meniscus scaffold was evaluated mechanically (tensile and compressive testing) and histologically after 16 and 32 weeks of implantation in an ovine total meniscectomy model (N = 20; 16 implants plus 4 meniscectomies, divided equally over the 2 time periods). The extent of cartilage damage was also measured on tibial plateaus by use of toluidine blue surface staining and on femoral condyles by use of Mankin scores on histological slides. Results: Scaffolds induced formation of neomeniscus tissue that remained intact and functional, with breaking loads approximating 250 N at both 16 and 32 weeks compared with 552 N for native menisci. Tensile stiffness values (99 and 74 N/mm at 16 and 32 weeks, respectively) were also comparable with those of the native meniscus (147 N/mm). The compressive modulus of the neomeniscus tissue (0.33 MPa at both 16 and 32 weeks) was significantly increased compared with unimplanted (time 0) scaffolds (0.15 MPa). There was histological evidence of extensive tissue ingrowth and extracellular matrix deposition, with immunohistochemical evidence of types I and II collagen. Based on significantly decreased surface damage scores as well as Mankin scores, the scaffold implants provided greater protection of articular cartilage compared with the untreated total meniscectomy. Conclusion: This novel fiber-reinforced meniscus scaffold can act as a functional meniscus replacement, with mechanical properties similar to those of the native meniscus, while protecting the articular cartilage of the knee from the extensive damage after a total meniscectomy. Clinical Relevance: This meniscus replacement scaffold has the potential to improve surgical treatment and provide better long-term outcomes for those suffering from severe meniscus damage.

One-Year Outcomes of Total Meniscus Reconstruction Using a Novel Fiber-Reinforced Scaffold in an Ovine Model

Background: Meniscus injuries and resulting meniscectomies lead to joint deterioration, causing pain, discomfort, and instability. Tissue-engineered devices to replace the meniscus have not shown consistent success with regard to function, mechanical integrity, or protection of cartilage. Purpose: To evaluate a novel resorbable polymer fiber–reinforced meniscus reconstruction scaffold in an ovine model for 52 weeks and assess its integrity, tensile and compressive mechanics, cell phenotypes, matrix organization and content, and protection of the articular cartilage surfaces. Study Design: Controlled laboratory study. Methods: Eight skeletally mature ewes were implanted with the fiber-reinforced scaffold after total meniscectomy, and 2 additional animals had untreated total meniscectomies. Animals were sacrificed at 52 weeks, and the explants and articular surfaces were analyzed macroscopically. Explants were characterized by ultimate tensile testing, confined compression creep testing, and biochemical, histological, and immunohistochemical analyses. Cartilage damage was characterized using the Mankin score on histologic slides from both the femur and tibia. Results: One sheep was removed from the study because of a torn extensor tendon; the remaining 7 explants remained fully intact and incorporated into the bone tunnels. All explants exhibited functional tensile loads, tensile stiffnesses, and compressive moduli. Fibrocartilagenous repair with both types 1 and 2 collagen were observed, with areas of matrix organization and biochemical content similar to native tissue. Narrowing in the body region was observed in 5 of 7 explants. Mankin scores showed less cartilage damage in the explant group (femoral condyle: 3.43 ± 0.79, tibial plateau: 3.50 ± 1.63) than in the meniscectomy group (femoral condyle: 8.50 ± 3.54, tibial plateau: 6.75 ± 2.47) and were comparable with Mankin scores at the previously reported 16- and 32-week time points. Conclusion: A resorbable fiber-reinforced meniscus scaffold supports formation of functional neomeniscus tissue, with the potential to prevent joint degeneration that typically occurs after total meniscectomy. Further studies with improvements to the initial mechanics of the scaffold and testing for longer time periods are warranted. Clinical Relevance: Meniscectomy is an extremely common orthopaedic procedure, and few options currently exist for the treatment of significant loss of meniscus tissue. Successful development of a tissue-engineered meniscus scaffold could substantially reduce the incidence of postmeniscectomy joint degeneration and the subsequent procedures used for its treatment.

Partial Meniscus Replacement with a Collagen-Hyaluronan Infused 3D Printed Polymeric Scaffold

IMPACT STATEMENT The only FDA-approved partial meniscus scaffold, the Collagen Meniscus Implant (CMI), is not approved for reimbursement by government and only reimbursable by certain private insurers. Scaffolds with improved mechanical properties and greater efficacy are needed. A previous study (Ghodbane, et al. DOI: 10.1002/jbm.b.34331) demonstrated the ability of our novel acellular, off-the shelf scaffold to restore knee biomechanics following partial meniscectomy, which could potentially decrease the risk of osteoarthritis following partial meniscectomy, providing the motivation for this study. This article presents a first-in-animal feasibility study.

Nonsurgical Treatment of De Quervain Tenosynovitis: A Prospective Randomized Trial:

Background: De Quervain tenosynovitis is commonly seen in patients who perform repetitive wrist ulnar deviation with thumb abduction and extension. Previous studies comparing nonsurgical options have contributed to a lack of consensus about ideal management. This study’s purpose was to analyze results in prospectively randomized patients treated with either corticosteroid injection (CSI) alone versus CSI with immobilization. Methods: Radial sided wrist pain, first dorsal compartment tenderness, and positive Finkelstein test were used to define De Quervain. Pain score of 4 or higher on a visual analog scale (VAS) was utilized for inclusion. Following exclusion criteria, patients underwent randomization into groups: (1) CSI alone; or (2) CSI with 3 weeks of immobilization. We followed at 3 weeks and 6 months for further evaluation, where resolution of symptoms and improvements in VAS and Disabilities of the Arm, Shoulder, and Hand (DASH) scores were assessed to evaluate treatment success. Results: Nine patients with CSI alone and 11 patients with CSI and immobilization were followed. At 6 months in both groups, patients experienced significant improvement in VAS and DASH scores, while 88% of patients with CSI alone and 73% of patients with CSI and immobilization experienced complete resolution of at least 2 out of 3 of their pretreatment symptoms. Between groups, outcomes were comparable except for resolution of radial-sided wrist pain, which was superior in patients with CSI alone (100% vs 64%). Conclusions: Immobilization following injection increases costs, may hinder activities of daily living, and did not contribute to improved patient outcomes in this study. Further prospective studies are warranted.

Tissue-Engineered Total Meniscus Replacement With a Fiber-Reinforced Scaffold in a 2-Year Ovine Model:

Background: Meniscus injuries and associated meniscectomies cause patients long-term pain and discomfort and can lead to joint deterioration. Purpose: To evaluate a collagen-hyaluronan sponge reinforced with synthetic resorbable polymer fiber for total meniscus reconstruction in a long-term ovine model. Study Design: Controlled laboratory study. Methods: Eleven skeletally mature sheep were implanted with the total meniscus scaffold. At 2 years, explants were evaluated biologically (radial/circumferential histology, immunofluorescence) and mechanically (compression, tension), and articular surfaces were examined for damage. Results: The fiber-reinforced scaffold induced formation of functional neomeniscus tissue that was intact in 8 of 11 animals. The implant was remodeled into organized circumferentially aligned collagen bundles to resist meniscus hoop stresses. Moreover, type II collagen and proteoglycan deposition near the inner margin suggested a direct response to compressive stresses and confirmed fibrocartilage formation. Cartilage damage was observed, but end-stage (severe) joint deterioration associated with meniscectomy was avoided, even with limitations regarding the ovine surgical procedure and postoperative care. Conclusion: A fiber-reinforced total meniscus replacement device induces formation of functional neomeniscus tissue that has the potential to prevent catastrophic joint deterioration associated with meniscectomy. Clinical Relevance: An off-the-shelf meniscus device that can be remodeled into functional tissue and thus prevent or delay the onset of osteoarthritis could address a widespread clinical need after meniscus injury.

Interference Screw Versus Suture Endobutton Fixation of a Fiber-Reinforced Meniscus Replacement Device in a Human Cadaveric Knee Model:

Background: Meniscal lesions represent one of the most common intra-articular knee injuries. Meniscus replacement devices are needed to restore load distribution and knee stability after meniscectomy. Fixation of these devices is crucial to the generation of hoop stresses and the distribution of loads in the joint. Purpose: To evaluate 2 different fixation techniques (suture endobutton and interference screw) for implantation of a novel meniscus device. Study Design: Controlled laboratory study. Methods: In 7 human cadaveric knees (aged 17-61 years), 1 anterior and 2 potential posterior tunnel locations were investigated, and both fixation techniques were tested in each tunnel. The native meniscus roots, devices fixed with a suture endobutton, and devices fixed with an interference screw were gripped with cryoclamps, and tibias were drilled and loaded into a custom jig. Samples were preloaded, preconditioned, loaded for 500 cycles (50-150 N), and tested in tension until failure. Results: For all 3 tunnels, suture fixation resulted in greater elongation (54.1%-150.7% greater; P < .05) during cyclic loading than interference screw fixation, which approximated the native roots. Both fixation techniques displayed ultimate tensile loads in the same range as native roots. However, stiffness of the suture fixation groups (36.5-41.6 N/mm) was only 28% to 37% of that of the interference screw fixation groups (98.7-131.6 N/mm), which had values approaching those of the native roots (anterior: 175.4 ± 24.2 N/mm; posterior: 157.6 ± 22.9 N/mm). Conclusion: Interference screw fixation was found to be superior to suture fixation with regard to elongation and stiffness, a finding that should be considered in the design and implantation of novel meniscus replacement devices. Clinical Relevance: With the emergence of various devices for total meniscus replacement, the establishment of fixation strategies is crucial for the generation of tensile hoop stresses and the efficacy of these approaches.

Negative outcomes of PLLA fiber-reinforced scaffolds in an ovine total meniscus replacement model

Our objective was to test the efficacy of collagen-hyaluronan scaffolds reinforced with poly(l-lactic acid) (PLLA) fibers in an ovine total meniscus replacement model. Scaffolds were implanted into 9 sheep (n = 1 at 8 weeks, n = 2 at 16 weeks, n = 3 at both 24, 32 weeks) following total medial meniscectomy. From 16 weeks on, explants were characterized by confined compression creep, histological, and biochemical analyses. Articular surfaces were observed macroscopically and damage was ranked histologically using the Mankin score. At sacrifice, three of the nine PLLA scaffolds had completely ruptured, and the intact scaffolds experienced progressive shape changes and severe narrowing in the body region at 16, 24, and 32 weeks. Aggregate compressive modulus and permeability did not improve with time. Histological and biochemical analyses showed significantly less extracellular matrix and less matrix organization compared to native tissue. Osteophytes, bone erosion, and cartilage damage were observed, increasing with time postimplantation. A buildup of lactic acid and/or the rapid loss of scaffold mechanical integrity due to PLLA degradation are probable causes for the joint abnormalities observed in this study. These results are in sharp contrast to those of our previous successful total meniscus replacement studies using polyarylate [p(DTD DD)] fiber-reinforced scaffolds. This suggests that PLLA fiber as produced in this study cannot be used as reinforcement for a meniscus replacement scaffold.

A Load-Sharing Tissue Engineered Meniscus Scaffold: One Year Outcome

Objectives: Arthroscopic partial meniscectomy is one of the most commonly performed orthopaedic procedures. Although the procedure provides good symptom relief, long term follow up suggests the procedure results in an early onset of degenerative knee arthritis in a significant percentage of patients. Currently, treatment options for lost meniscal tissue are extremely limited and those available do not provide a long term solution. Therefore, there exists a need for a functional meniscus replacement in order to prevent joint deterioration. The objective of this project was to test a cross-linked collagen-hyaluronan sponge reinforced with synthetic, resorbable poly(DTD DD) fibers for meniscal implantation in an ovine model. Methods: Meniscus scaffolds were fabricated from poly(DTD DD) fibers woven into a semi-lunar wedge shape with extended tails for rigid tibial fixation. A dispersion of hyaluronic acid and type I bovine collagen was injected into the woven fiber scaffold. The scaffold was then lyophilized, crosslinked, and irradiated. The time-zero mechanical properties of the scaffold were evaluated with ultimate tensile testing and compression creep testing, and for load sharing function with a novel hoop stress evaluation and joint pressure distribution using Tekscan monitoring. The scaffolds were evaluated in an in vivo ovine model. A total medial meniscectomy was performed in the right hind leg of 30 sheep. Twenty-four of these sheep received a tissue engineered scaffold. The scaffold was anchored to the tibial plateau at the anterior and posterior root locations with titanium interference screws and sutured to the medial capsule. The remaining 6 sheep did not receive an implant and served as controls. Eight experimental and two control sheep were sacrificed at 16, 32 and 52 weeks. Scaffolds and adjacent articular cartilage underwent comprehensive mechanical and histological evaluation. Results: Pre-implantation characterization: Ultimate tensile strength of the implant was 660 N. The compressive modulus was 0.15 MPa. Hoop stress evaluation demonstrated a linear correlation between joint axial load and tensile stress in the implant. Tekscan evaluation demonstrated the implant increased joint contact area and decreased peak contact stress. In vivo evaluation demonstrated, at all time points, all 24 implants were fully intact and well healed to the surrounding capsule and maintained the meniscus-like shape (Figure 1). Gross and histological evaluation of the articular cartilage adjacent to the implant demonstrated minimal degenerative change in experimental knees. Control knees demonstrated advanced cartilage degradation adjacent to the meniscal resection. Robust tissue ingrowth into the implants was histologically demonstrated with tissue deposition occurring in a pattern consistent with tensile stresses in the implant. The tensile strength of the scaffold explant was 255 N at 16 weeks and 237 N at 32 weeks and 210 N at 52 weeks. The compressive modulus was 0.29 MPa at 16 weeks, 0.34 MPa at 32 weeks, and 0.49 MPa at 52 weeks. Conclusion: The results of this study support the feasibility of a tissue engineered load sharing scaffold for treatment of significant meniscal damage. The scaffold has the potential to prevent degenerative changes that occur after meniscectomy. Longer term studies will be necessary to confirm the true chondroprotective capabilities of this scaffold.