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Effective early disease modifying options for osteoarthritis remain lacking. Tissue engineering approach to generate cartilage in vitro has emerged as a promising option for articular cartilage repair and regeneration. Signaling molecules and matrix modifying agents, derived from knowledge of cartilage development and homeostasis, have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage. Clinical translation of neocartilage faces challenges, such as phenotypic instability of the engineered cartilage, poor integration, inflammation, and catabolic factors in the arthritic environment; these can all contribute to failure of implanted neocartilage. A comprehensive understanding of signaling molecules involved in osteoarthritis pathogenesis and their actions on engineered cartilage will be crucial. Thus, while it is important to continue deriving inspiration from cartilage development and homeostasis, it has become increasingly necessary to incorporate knowledge from osteoarthritis pathogenesis into cartilage tissue engineering.

Introduction With the advances and improvement of computer-assisted surgery devices, computer-guided pedicle screws insertion has been applied to the lumbar, thoracic and cervical spine. The purpose of the present study was to perform a systematic review of all available prospective evidence regarding pedicle screw insertion techniques in the thoracic and lumbar human spine. Materials and methods We considered all prospective in vivo clinical studies in the English literature that assessed the results of different pedicle screw placement techniques (free-hand technique, fluoroscopy guided, computed tomography (CT)-based navigation, fluoro-based navigation). MEDLINE, OVID, and Springer databases were used for the literature search covering the period from January 1950 until May 2010. Results 26 prospective clinical studies were eventually included in the analysis. These studies included in total 1,105 patients in which 6,617 screws were inserted. In the studies using free-hand technique, the percentage of the screws fully contained in the pedicle ranged from 69 to 94%, with the aid of fluoroscopy from 28 to 85%, using CT navigation from 89 to 100% and using fluoroscopy-based navigation from 81 to 92%. The screws positioned with free-hand technique tended to perforate the cortex medially, whereas the screws placed with CT navigation guidance seemed to perforate more often laterally. Conclusions In conclusion, navigation does indeed exhibit higher accuracy and increased safety in pedicle screw placement than free-hand technique and use of fluoroscopy.

Significance The inadequate mechanical properties of engineered tissues have prevented related therapies from clinical translation. Collagen cross-links correlate with the mechanical integrity of tissues; however, addressing the weakness of neotissues through enhancing collagen cross-links has not received the attention it deserves. The present study demonstrates, both in vitro and in vivo, that improvements in the mechanical properties of native and engineered tissues can be attained using endogenous (hypoxia-mediated) and exogenous application of lysyl oxidase, which is the enzyme responsible for collagen cross-linking. By promoting an ∼16-fold increase in collagen cross-linking and, concomitantly, an approximately fivefold enhancement in the neotissue’s mechanical properties, this work creates new prospects for regenerative medicine. The methods developed here work across a spectrum of collagen-rich tissues and are clinically applicable. The inability to recapitulate native tissue biomechanics, especially tensile properties, hinders progress in regenerative medicine. To address this problem, strategies have focused on enhancing collagen production. However, manipulating collagen cross-links, ubiquitous throughout all tissues and conferring mechanical integrity, has been underinvestigated. A series of studies examined the effects of lysyl oxidase (LOX), the enzyme responsible for the formation of collagen cross-links. Hypoxia-induced endogenous LOX was applied in multiple musculoskeletal tissues (i.e., cartilage, meniscus, tendons, ligaments). Results of these studies showed that both native and engineered tissues are enhanced by invoking a mechanism of hypoxia-induced pyridinoline (PYR) cross-links via intermediaries like LOX. Hypoxia was shown to enhance PYR cross-linking 1.4- to 6.4-fold and, concomitantly, to increase the tensile properties of collagen-rich tissues 1.3- to 2.2-fold. Direct administration of exogenous LOX was applied in native cartilage and neocartilage generated using a scaffold-free, self-assembling process of primary chondrocytes. Exogenous LOX was found to enhance native tissue tensile properties 1.9-fold. LOX concentration- and time-dependent increases in PYR content (∼16-fold compared with controls) and tensile properties (approximately fivefold compared with controls) of neocartilage were also detected, resulting in properties on par with native tissue. Finally, in vivo subcutaneous implantation of LOX-treated neocartilage in nude mice promoted further maturation of the neotissue, enhancing tensile and PYR content approximately threefold and 14-fold, respectively, compared with in vitro controls. Collectively, these results provide the first report, to our knowledge, of endogenous (hypoxia-induced) and exogenous LOX applications for promoting collagen cross-linking and improving the tensile properties of a spectrum of native and engineered tissues both in vitro and in vivo.

Background Anterior cruciate ligament (ACL) rupture is a common orthopedic injury, occurring in roughly 68.6 per 100,000 persons annually, with the primary treatment option being ACL reconstruction. However, debate remains about the appropriate graft type for restoring the native biomechanical properties of the knee. Furthermore, plastic graft elongation may promote increased knee laxity and instability without rupture. This study aims to investigate the plastic properties of common ACL-R graft options. Methods Patellar tendon (PT), hamstring tendon (HT), and quadriceps tendon (QT) grafts were harvested from 11 cadaveric knees (6 male and 5 female) with a mean age of 71(range 55–81). All grafts were mechanically tested under uniaxial tension until failure to determine each graft’s elastic and plastic biomechanical properties. Results Mechanically, the QT graft was the weakest, exhibiting the lowest failure force and the lowest failure stress (QT < HT, p  = 0.032). The PT was the stiffest of the grafts, having a significantly higher stiffness (PT > QT, p  = 0.0002) and Young’s modulus (PT > QT, p  = 0.001; PT > HT, p  = 0.041). The HT graft had the highest plastic elongation at 4.01 ± 1.32 mm (HT > PT, p  = 0.002). The post-yield behavior of the HT tendon shows increased energy storage capabilities with the highest plastic energy storage (HT > QT, p  = 0.012) and the highest toughness (HT > QT, p  = 0.032). Conclusion Our study agrees with prior studies indicating that the failure load of all grafts is above the requirements for everyday activities. However, grafts may be susceptible to yielding before failure during daily activities. This may result in the eventual loss of functionality for the neo-ACL, resulting in increased knee laxity and instability.

Abundance and accessibility render skin-derived stem cells an attractive cell source for tissue engineering applications. Toward assessing their utility, the variability of constructs engineered from human dermis-isolated adult stem (hDIAS) cells was examined with respect to different anatomical locations (foreskin, breast, and abdominal skin), both in vitro and in a subcutaneous, athymic mouse model. All anatomical locations yielded hDIAS cells with multi-lineage differentiation potentials, though adipogenesis was not seen for foreskin-derived hDIAS cells. Using engineered cartilage as a model, tissue engineered constructs from hDIAS cells were compared. Construct morphology differed by location. The mechanical properties of human foreskin- and abdominal skin-derived constructs were similar at implantation, remaining comparable after 4 additional weeks of culture in vivo. Breast skin-derived constructs were not mechanically testable. For all groups, no signs of abnormality were observed in the host. Addition of aggregate redifferentiation culture prior to construct formation improved chondrogenic differentiation of foreskin-derived hDIAS cells, as evident by increases in glycosaminoglycan and collagen contents. More robust Alcian blue staining and homogeneous cell populations were also observed compared to controls. Human DIAS cells elicited no adverse host responses, reacted positively to chondrogenic regimens, and possessed multi-lineage differentiation potential with the caveat that efficacy may differ by anatomical origin of the skin. Taken together, these results suggest that hDIAS cells hold promise as a potential cell source for a number of tissue engineering applications.

Carpometacarpal (CMC) dislocations without associated fractures of the adjacent bones are extremely infrequent injuries. Dorsal or volar dislocations occur after high-energy injuries and may lead to early post-traumatic arthritis and carpal instability. The purpose of this study was to present a case of dorsal dislocation of both the fourth and fifth CMC joints that were treated with closed reduction and casting. A 31-year-old man developed severe acute pain, functional limitation, and deformity of the wrist after falling from a height. The clinical examination revealed intense localized tenderness, swelling, and palpable prominence over the fourth and fifth metacarpals. Standard anteroposterior and lateral views demonstrated dislocations of the examined CMC joints without any accompanied fracture. The injury was treated with anatomic closed reduction and cast immobilization for overall five weeks followed by early mobilization. Twelve weeks after injury, the patient had regained grip strength, and six months post-traumatically he satisfactorily returned to his previous hard labor-intensive activities without any functional deficits or chronic pain. Conclusively, CMC dislocations can be treated conservatively in case of early diagnosis and stable anatomic closed reduction.

Purpose Knee effusion is a common symptom in various knee disorders of both traumatic and non-traumatic aetiology. Although intra-articular aspiration is a widespread treatment approach, its beneficial effect has not been confirmed by a randomized controlled study. The purpose was to evaluate the effectiveness and safety of joint aspiration in acute knee effusion, in relation to traumatic or non-traumatic aetiology. Methods One hundred and sixty-seven consecutive patients with acute knee joint effusion were allocated in a randomized controlled fashion into two groups. In the first group, joint aspiration was performed, while in the second group, no aspiration was performed. Range of motion, pain relief, use of analgesics and oedema were evaluated post management. The Knee Society Score and the International Knee Documentation Committee Subjective Evaluation Form were also obtained. In addition, a subgroup analysis of our results in relation to the presence of trauma or not was performed. Results Aspiration exhibited a temporary improvement in all clinical parameters evaluated, especially in the post-traumatic effusion. However, this improvement lasted only for the first week, due to the early re-accumulation of the effusion. There was no difference between the different groups regarding the clinical outcome in neither trauma or non-trauma patients at the end of the follow-up period. Aspiration aided in earlier establishment of the diagnosis in the non-trauma cases of effusion. Conclusions Aspiration resulted in only temporary improvement of the outcome in the treatment of traumatic or not traumatic knee effusion. Aspiration is suggested in effusions of unknown origin in order to establish the diagnosis and for immediate clinical relief. However, aspiration should be performed with consideration in the presence of trauma. Level of evidence Therapeutic study, Level I.

Tissue-engineered musculoskeletal soft tissues typically lack the appropriate mechanical robustness of their native counterparts, hindering their clinical applicability. With structure and function being intimately linked, efforts to capture the anatomical shape and matrix organization of native tissues are imperative to engineer functionally robust and anisotropic tissues capable of withstanding the biomechanically complex in vivo joint environment. The present study sought to tailor the use of passive axial compressive loading to drive matrix synthesis and reorganization within self-assembled, shape-specific fibrocartilaginous constructs, with the goal of developing functionally anisotropic neotissues. Specifically, shape-specific fibrocartilaginous neotissues were subjected to 0, 0.01, 0.05, or 0.1 N axial loads early during tissue culture. Results found the 0.1-N load to significantly increase both collagen and glycosaminoglycan synthesis by 27% and 67%, respectively, and to concurrently reorganize the matrix by promoting greater matrix alignment, compaction, and collagen crosslinking compared with all other loading levels. These structural enhancements translated into improved functional properties, with the 0.1-N load significantly increasing both the relaxation modulus and Young's modulus by 96% and 255%, respectively, over controls. Finite element analysis further revealed the 0.1-N uniaxial load to induce multiaxial tensile and compressive strain gradients within the shape-specific neotissues, with maxima of 10.1%, 18.3%, and −21.8% in the XX-, YY-, and ZZ-directions, respectively. This indicates that strains created in different directions in response to a single axis load drove the observed anisotropic functional properties. Together, results of this study suggest that strain thresholds exist within each axis to promote matrix synthesis, alignment, and compaction within the shape-specific neotissues. Tailoring of passive axial loading, thus, presents as a simple, yet effective way to drive in vitro matrix development in shape-specific neotissues toward more closely achieving native structural and functional properties.

Purpose Implant loosening represents one of the major factors of total hip arthroplasty (THA) failure. The purpose of this study was to identify specific markers indicative of septic and aseptic loosening in patients that underwent THA. Methods Flow cytometry was performed in blood samples of 20 patients with loosening (10 septic/10 aseptic). Additional ten healthy individuals served as a control group. The expression of surface receptors and cytoplasmic molecules in patients that underwent THA was quantified. CD62L, CD18, CD11a, CD11b and CD11c expressions were evaluated and correlated with the presence of loosening. Also, a comparison between septic and aseptic THA loosening characteristics was performed. Results The mean fluorescence intensity (MFI) for CD18 was significantly decreased on all leukocytes subsets in both septic and aseptic loosening compared to control group ( p  < 0.005 in all occasions). Patients with aseptic loosening showed increased MFI for CD11b in granulocytes and for CD11c in monocytes and granulocytes compared to the control and aseptic group ( p  = 0.02 and p  = 0.005, respectively). In patients with septic loosening, an increase in MFI for CD11c was observed in monocytes only compared to control group ( p  = 0.03). The comparison between aseptic and septic loosening showed significantly lower CD18 MFI value in granulocytes for aseptic loosening ( p  = 0.008). Conclusions CD11 and CD18 MFI values appear to be indicative of loosening in THAs. Flow cytometry markers can be used to identify THA loosening, as well as to differentiate between septic and aseptic cases.

Introduction The purpose of this study was to evaluate the feasibility of transferring the pectoralis minor (PM) in its entirety and assess its relationship with the musculocutaneous nerves (MCN) and axillary nerves (AXN). Methods Sixteen fresh transthoracic cadaver specimens were used. After PM transfer, the following measures were obtained: (a) the distance between the coracoid process (CP) and the subscapularis insertion on the lesser tubercle during external, neutral, and internal rotation. (b) The distances between the CP and PM, PM and musculocutaneous nerve, and PM and the axillary nerve. All measurements were performed using a precision caliper by two independent and blind-to-each-other findings observers. Results The median distance between the CP and PM muscles was 24 ± 7.7 mm, while the width of the coracoid was 24 ± 5.2 mm. PM-MCN distance was 23.25 ± 21.9 mm, CP-MCN distance was 72.1 ± 32.4 mm, and PM-AXN distance was 4.9 ± 0.7 mm. The distance between the coracoid process and lesser tuberosity varied by rotation: 29.2 ± 5.5 mm in internal rotation, 41.1 ± 8.9 mm in neutral rotation, and 51.1 ± 10.7 mm in external rotation. The distance significantly increased between internal and neutral or external rotation (p <0.05), but no significant difference was observed between neutral and external rotation (p > 0.05). Conclusion The distance between the coracoid process and lesser tuberosity increased considerably only between internal and neutral or external rotation positions. Additionally, the importance of identifying the musculocutaneous and axillary nerves and their branches when transferring the pectoralis minor should be highlighted.