Ohan S. Manoukian

Analysis of a New All-Inside Versus Inside-Out Technique for Repairing Radial Meniscal Tears

PURPOSE The purpose of this study was to compare gap formation, strength, and stiffness of repaired radial tears of the meniscus treated using a new all-inside technique versus a traditional inside-out suture technique. METHODS Radial tears were created in 36 fresh-frozen porcine menisci. Repairs were performed using a novel all-inside suture-based meniscal repair device or an inside-out technique. The repairs were tested for cyclic loading and load to failure. The displacement, response to cyclic loading (100, 300, and 500 cycles), and mode of failure were recorded, and the constructs stiffness was calculated. RESULTS The all-inside repairs using the novel device resulted in a significantly lower displacement (gap formation) after 100, 300, and 500 cycles (P = .002, P = .001, and P = .001, respectively). The ultimate load to failure was significantly greater for the all-inside repairs (111.61 N v 95.01 N; P = .03). The all-inside repairs showed greater stiffness (14.53 N/mm v 11.19 N/mm; P = .02). The all-inside repairs failed most often by suture breakage (suture failure). The inside-out repairs failed most commonly when the suture pulled through the tissue (tissue failure) (P < .001). CONCLUSIONS For repair of radial tears of the meniscus, the vertical suture configuration created by the all-inside technique resulted in lower displacement, higher load to failure, and greater stiffness compared with the horizontal inside-out technique. CLINICAL RELEVANCE In a porcine specimen meniscus repair model, the biomechanical properties of a vertical all-inside technique were superior to that of a horizontal inside-out technique. Future studies of biomechanical and clinical outcomes in human meniscal repairs with this device are warranted to explore whether this repair method is valuable to clinical practice and patient outcomes.

Peripheral Nerve Regeneration Strategies: Electrically Stimulating Polymer Based Nerve Growth Conduits.

Treatment of large peripheral nerve damages ranges from the use of an autologous nerve graft to a synthetic nerve growth conduit. Biological grafts, in spite of many merits, show several limitations in terms of availability and donor site morbidity, and outcomes are suboptimal due to fascicle mismatch, scarring, and fibrosis. Tissue engineered nerve graft substitutes utilize polymeric conduits in conjunction with cues both chemical and physical, cells alone and or in combination. The chemical and physical cues delivered through polymeric conduits play an important role and drive tissue regeneration. Electrical stimulation (ES) has been applied toward the repair and regeneration of various tissues such as muscle, tendon, nerve, and articular tissue both in laboratory and clinical settings. The underlying mechanisms that regulate cellular activities such as cell adhesion, proliferation, cell migration, protein production, and tissue regeneration following ES is not fully understood. Polymeric constructs that can carry the electrical stimulation along the length of the scaffold have been developed and characterized for possible nerve regeneration applications. We discuss the use of electrically conductive polymers and associated cell interaction, biocompatibility, tissue regeneration, and recent basic research for nerve regeneration. In conclusion, a multifunctional combinatorial device comprised of biomaterial, structural, functional, cellular, and molecular aspects may be the best way forward for effective peripheral nerve regeneration.

Biomechanical Evaluation of an All-Inside Suture-Based Device for Repairing Longitudinal Meniscal Tears

PURPOSE A device for all-inside suture-based meniscal repairs has been introduced (NovoStitch; Ceterix, Menlo Park, CA) that passes the suture vertically through the meniscus, thereby encircling the tear, and does not require an additional incision or extra-capsular anchors. Our aim was to compare this all-inside suture-based repair with an inside-out suture repair and an all-inside anchor-based repair (FasT-Fix 360°; Smith & Nephew, Andover, MA). METHODS Longitudinal tears were created in 36 fresh-frozen porcine menisci. Repairs were performed using an all-inside suture-based meniscal repair device, an all-inside anchor-based repair, and an inside-out suture repair. They were tested with cyclic loading and load-to-failure testing. The displacement, response to cyclic loading (100, 300, and 500 cycles), and mode of failure were recorded. The stiffness of the constructs was calculated as well. RESULTS The all-inside suture-based repairs and the inside-out repairs showed significantly higher loads to failure than the all-inside anchor-based repairs. The stiffness values for the 3 repairs were not different. There were no differences in initial displacement. After 100, 300, and 500 cycles, the inside-out repair had higher gap formation (displacement) than the other 2 groups. Suture failure was the predominant mode of failure across all repair techniques. CONCLUSIONS The all-inside suture-based repairs and inside-out repairs did not exhibit different load-to-failure values. In addition, the all-inside suture-based repairs and the all-inside anchor-based repairs did not exhibit different displacement values during cyclic loading. CLINICAL RELEVANCE When addressing a longitudinal meniscal tear, surgeons should consider biomechanical data of various repair devices and techniques in their decision-making process to maximize the mechanical strength and healing probability of the repair.

Electrospun Nanofiber Scaffolds and Their Hydrogel Composites for the Engineering and Regeneration of Soft Tissues

Electrospinning has emerged as a simple, elegant, and scalable technique that can be used to fabricate polymeric nanofibers. Pure polymers as well as blends and composites of both natural and synthetic ones have been successfully electrospun into nanofiber matrices for many biomedical applications. Tissue-engineered medical implants, such as polymeric nanofiber scaffolds, are potential alternatives to autografts and allografts, which are short in supply and carry risks of disease transmission. These scaffolds have been used to engineer various soft tissues, including connective tissues, such as skin, ligament, and tendon, as well as nonconnective ones, such as vascular, muscle, and neural tissue. Electrospun nanofiber matrices show morphological similarities to the natural extracellular matrix (ECM), characterized by ultrafine continuous fibers, high surface-to-volume ratios, high porosities, and variable pore-size distributions. The physiochemical properties of nanofiber matrices can be controlled by manipulating electrospinning parameters so that they meet the requirements of a specific application.Nanostructured implants show improved biological performance over bulk materials in aspects of cellular infiltration and in vivo integration, taking advantage of unique quantum, physical, and atomic properties. Furthermore, the topographies of such scaffolds has been shown to dictate cellular attachment, migration, proliferation, and differentiation, which are critical in engineering complex functional tissues with improved biocompatibility and functional performance. This chapter discusses the use of the electrospinning technique in the fabrication of polymer nanofiber scaffolds utilized for the regeneration of soft tissues. Selected scaffolds will be seeded with human mesenchymal stem cells (hMSCs), imaged using scanning electron and confocal microscopy, and then evaluated for their mechanical properties as well as their abilities to promote cell adhesion, proliferation , migration, and differentiation.

Osteochondral scaffold combined with aligned nanofibrous scaffolds for cartilage regeneration

Osteochondral defect repair poses a significant challenge in its reconstruction as the damage is presented in both articular cartilage and the underlying subchondral bone. Tissue engineering approaches have utilized various scaffolds in combination of stem cells and growth factors to regenerate the defect. Still a significant challenge remains in creating a scaffold structure that supports the proliferation and differentiation of bone marrow stromal cells (BMSCs) into chondrocytes and osteoblasts while providing the appropriate mechanical stability. The present manuscript reports the fabrication and characterization of a biphasic scaffold system derived from biodegradable polymers such as poly(lactic acid-glycolic acid) (PLGA) as a hard shell and polycaprolactone (PCL) a soft component. Collectively this biphasic scaffold was able to withstand physiological loads up to 10000 cycles in a cyclic compressive test. The scaffold surface was decorated with PCL aligned nanofibers contacting chondroitin sulfate and hyaluronic acid and nanofibers were cross-linked via carbodiimide linkages to retain these bioactive molecules over the culture period. The present study aims to show the potential of these bioactive scaffolds for the repair of osteochondral defects. Scaffolds were characterized by Fourier transform infra-red spectroscopy, optical microscopy and cyclic compressive testing. Primary rat bone marrow stem cells were seeded onto scaffolds and cell proliferation and differentiation was evaluated using RTPCR and immunohistochemistry. RT-PCR indicated that the scaffold was able to stimulate the different regions of osteochondral tissue: collagen type II and aggrecan expression in the cartilage region and BMP-2 in the bone region. Similarly protein secretion with induced alignment was confirmed with immunofluorescence imaging. This novel hybrid scaffold shows promising results in the regeneration of cartilage tissue as well as the underlying subchondral bone.

Posterior Capsular Plication Constrains the Glenohumeral Joint by Drawing the Humeral Head Closer to the Glenoid and Resisting Abduction

Background: Shoulder pain is a common problem, with 30% to 50% of the American population affected annually. While the majority of these shoulder problems improve, there is a high rate of recurrence, as 54% of patients experience persistent symptoms 3 years after onset. Purpose: Posterior shoulder tightness has been shown to alter glenohumeral (GH) kinematics. Clinically, posterior shoulder contractures result in a significant loss of internal rotation and abduction (ABD). In this study, the effect of a posterior capsular contracture on GH kinematics was investigated using an intact cadaveric shoulder without violating the joint capsule or the rotator cuff. Study Design: Controlled laboratory study. Methods: Glenohumeral motion, humeral load, and subacromial contact pressure were measured in 6 fresh-frozen left shoulders during passive ABD from 60° to 100° using an automated robotic upper extremity testing system. Baseline values were compared with the experimental condition in which the full thickness of posterior tissues was plicated without decompressing the joint capsule. Results: Posterior soft tissue plication resulted in increased compression between the humeral head and the glenoid (axial load) at 90° of ABD. Throughout ABD, the posterior contracture increased the anterior and superior moment on the humeral head, but it did not change the GH kinematics in this intact model. As a result, there was no increase in the subacromial contact pressure during ABD with posterior plication. Conclusion: In an intact cadaveric shoulder, posterior contracture does not alter GH motion or subacromial contact pressure during passive ABD. By tightening the soft tissue envelope posteriorly, there is an increase in compressive load on the articular cartilage and anterior/superior force on the humeral head. These findings suggest that subacromial impingement in the setting of a posterior soft tissue contracture may result from alterations in scapulothoracic motion, not changes in GH kinematics. Clinical Relevance: This investigation demonstrates that posterior capsular plication increases the axial load on the shoulder joint during ABD. While a significant difference from baseline was observed in the plicated condition, posterior capsular plication did not change GH motion or subacromial contact pressure significantly.

Biodegradable polymeric injectable implants for long-term delivery of contraceptive drugs: ARTICLE

Development of injectable, long-lasting, contraceptive drug delivery formulations and implants are highly desired to avoid unplanned pregnancies while improving patient compliance and reducing adverse side effects and treatment costs. The present study reports on the fabrication and characterization of two levonorgestrel (LNG) microsphere injectable formulations. Poly(ε-caprolactone) (PCL) with 12.5% and 24% (w/w) LNG were fabricated into microspheres, measuring 300±125 μm, via the oil-in-water (o/w) emulsion solvent evaporation technique. Formulations showed sustained drug release up to 120 days. FTIR, XRD, DSC, and TGA confirmed the absence of LNG chemical interaction with PCL as well as its molecular level distribution. The in vitro release of LNG was calculated to be Fickian diffusion controlled and properly characterized. The inclusion of multiple elevated release temperatures allowed for the application of the Arrhenius model to calculate drug release constants and representative sampling intervals, demonstrating the use of elevated temperatures for accelerated-time drug release studies.

Biomaterials for Tissue Engineering and Regenerative Medicine

Tissue engineering is a field of study that focuses on the integration of scaffolds, cells, and bioactive factors to produce functional biological tissues. Novel biomaterials provide the foundation for the development of tissue engineering and regenerative medicine. Through the use and improvement of these biocompatible materials, biomedical engineers and researchers have been able to develop treatments that address unmet clinical needs as well as improve earlier practices. These treatments address a wide range of disciplines from musculoskeletal applications to tissue regeneration. An advantage is that the Food and Drug Administration has approved several biomaterials, both natural and synthetic, as compliant for use in the human body. This prior approval enables researchers to improve the use of biomaterials in their approved applications, and advance the quality of treatment in a shorter period of time. Scientists, engineers, and clinicians all work in a collaborative effort to design treatments with biomaterials that closely resemble human tissues, and promote optimal repair or regeneration at the targeted site. This article will describe some of the most commonly used natural and synthetic biomaterials including their uses, advantages, disadvantages, and applications for various tissue engineering and regenerative medicine applications.

Hyperflexion and Femoral Interference Screw Insertion in ACL Reconstruction

Background: In anatomic anterior cruciate ligament (ACL) reconstructions produced with flexible reamers and no knee hyperflexion, it is unknown whether knee hyperflexion is necessary for femoral interference screw insertion. Purpose: To compare femoral screw-graft divergence in anatomic ACL reconstructions with endoscopic interference screws placed without knee hyperflexion and with the use of flexible versus rigid screwdrivers. Study Design: Controlled laboratory study. Methods: Ten matched pairs of cadaveric knees had bone-tendon-bone graft ACL reconstructions with anatomic femoral tunnels. The knees were flexed to 90°. Femoral interference screws (7 × 20 mm) were placed in pairs of knees: in 1 knee with a flexible screwdriver and in the opposite knee with a rigid screwdriver. Graft-screw divergence was imaged with computed tomography scans and tested with cyclic and static biomechanical tests. Results: The mean screw-graft divergence was 12.07° ± 4.04° with the rigid screwdriver and 10.68° ± 3.23° with the flexible screwdriver (P = .35). The cyclic tests with screws placed by a rigid screwdriver had a mean increase in displacement of 0.56 ± 0.20 mm. For screws placed with the flexible screwdriver, the mean increase in displacement was 0.58 ± 0.32 mm (P = .66). Yield load was 393.3 ± 95.1 N for screws placed by a rigid screwdriver and 408.2 ± 119.0 N for screws inserted with the flexible screwdriver (P = .78). Maximum load was 523.1 ± 88.7 N for screws placed by a rigid screwdriver and 467.1 ± 107.3 N for screws inserted with the flexible screwdriver (P = .09). Conclusion: With either a rigid or a flexible screwdriver, there were no significant effects on screw divergence or fixation strength. Clinical Relevance: Knees can be kept at 90° during endoscopic femoral interference screw insertion. The use of a traditional rigid or flexible screwdriver will not affect screw-graft divergence or fixation strength.

Nanomaterials/Nanocomposites for Osteochondral Tissue

For many years, the avascular nature of cartilage tissue has posed a clinical challenge for replacement, repair, and reconstruction of damaged cartilage within the human body. Injuries to cartilage and osteochondral tissues can be due to osteoarthritis, sports, aggressive cancers, and repetitive stresses and inflammation on wearing tissue. Due to its limited capacity for regeneration or repair, there is a need for suitable material systems which can recapitulate the function of the native osteochondral tissue physically, mechanically, histologically, and biologically. Tissue engineering (TE) approaches take advantage of principles of biomedical engineering, clinical medicine, and cell biology to formulate, functionalize, and apply biomaterial scaffolds to aid in the regeneration and repair of tissues. Nanomaterial science has introduced new methods for improving and fortifying TE scaffolds, and lies on the forefront of cutting-edge TE strategies. These nanomaterials enable unique properties directly correlated to their sub-micron dimensionality including structural and cellular advantages. Examples include electrospun nanofibers and emulsion nanoparticles which provide nanoscale features for biomaterials, more closely replicating the 3D extracellular matrix, providing better cell adhesion, integration, interaction, and signaling. This chapter aims to provide a detailed overview of osteochondral regeneration and repair using TE strategies with a focus on nanomaterials and nanocomposites.