Browsing by Author "Scheu, Maximiliano"
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Item A rabbit model demonstrates the influence of cartilage thickness on intra-articular drug delivery and retention within cartilage(Orthopaedic Research Society. Published by Wiley Periodicals, Inc., 2015) Bajpayee, Ambika; Scheu, Maximiliano; Grodzinsky, Alan; Porter, RyanFor evaluation of new approaches to drug delivery into cartilage, the choice of an animal model is critically important. Since cartilage thickness varies with animal size, different levels of drug uptake, transport and retention should be expected. Simple intra-articular injection can require very high drug doses to achieve a concentration gradient high enough for drug diffusion into cartilage. New approaches involve nanoparticle delivery of functionalized drugs directly into cartilage; however, diffusion-binding kinetics proceeds as the square of cartilage thickness. In this study, we demonstrate the necessity of using larger animals for sustained intra-cartilage delivery and retention, exemplified by intra-articular injection of Avidin (drug-carrier) into rabbits and compared to rats in vivo. Penetration and retention of Avidin within cartilage is greatly enhanced by electrostatic interactions. Medial tibial cartilage was the thickest of rabbit cartilages, which generated the longest intra-cartilage half-life of Avidin (τ1/2 = 154 h). In contrast, Avidin half-life in thinner rat cartilage was 5-6 times shorter (τ1/2 ∼ 29 h). While a weak correlation (R(2) = 0.43) was found between Avidin half-lives and rabbit tissue GAG concentrations, this correlation improved dramatically (R(2) = 0.96) when normalized to the square of cartilage thickness, consistent with the importance of cartilage thickness to evaluation of drug delivery and retention.Item Anterior cruciate ligament regeneration using mesenchymal stem cells and collagen type I scaffold in a rabbit model(Springer, 2014) Figueroa, David; Espinosa, Maximiliano; Calvo, Rafael; Scheu, Maximiliano; Vaisman, Alex; Gallegos, Marcela; Conget, PaulettePurpose: The objective of this study was to determine whether using mesenchymal stem cells (MSC) seeded in a collagen type I scaffold would be sufficient to regenerate the torn anterior cruciate ligament (ACL). Methods: Anterior cruciate ligament transection was performed on both knees in 10 New Zealand rabbits and then repaired with as follows: suture alone (suture-treated group, n = 6), suture associated with collagen type I scaffold (collagen type I scaffold-treated group, n = 8) or suture associated with autologous MSC seeded on collagen type I scaffold (MSC/collagen type I scaffold-treated group, n = 6). At 12-week post-intervention, the animals were killed and the ACLs were characterised macroscopically and histologically. Data of the 3 groups were against normal ACL (normal group, n = 10). Results: Macroscopic observation found that in MSC/collagen type I scaffold group, 33 % of specimens showed a complete ACL regeneration, with a tissue similar to the normal ACL. Regeneration was not observed in the group treated with suture alone or associated with collagen type I scaffold without cells. In the latter, only a reparative attempt at the ends was observed. Histological analysis of the regenerated ACL showed a tissue with organised collagen and peripheric vessels. Conclusions: These results provide evidence that the use of MSC seeded in a collagen type I scaffold in the treatment of ACL injuries is associated with an enhancement of ligament regeneration. This MSC-based technique is a potentially attractive tool for improving the treatment of ACL ruptures.Item No association between positive intraoperative allograft cultures and infection rates after reconstructive knee ligament surgery(2018) Schmidt-Hebbel, Andres; Gomez, Carlos; Aviles, Carolina; Herbst, Elmar; Scheu, Maximiliano; Ferrer, Gonzalo; Espinoza, GonzaloBackground: Several reports of severe infections associated with allograft tissue in knee reconstructivesurgery have led many surgeons to consider routine intraoperative culture of allograft tissue before implantation. Thus, the purpose of this study was to determine the prevalence of positive soft tissue allograft cultures in reconstructive knee surgery, and evaluate its association with surgical site infection. Methods: Retrospective study of 202 patients who underwent knee reconstructive ligament surgeries, including revisions, between January 2013 and July 2017. Intraoperative culture results were obtained and the report of a surgical site infection during follow-up was recorded. Patients without cultures were excluded. A priori power analysis was performed. The association between positive culture results and development of surgical site infection was evaluated usingFisher's Exact test (P b 0.05). Results: A total of 300 allografts were implanted in 202 patients. Mean average follow-up was 32.9 ± 12.5 (range 13 to 57.9) months. Sixteen patients had positive intraoperative allograft cultures (7.9%). The most frequently isolated organism was Bacillus species (six cultures); none of these patients presented with clinical signs of infection. Nine patients developed surgical site infections and were treated with oral antibiotics, and one patient developed septic arthritis that required surgical debridement of the implanted graft; all of these patients had a negative soft tissue allograft culture. No significant association was found between a positive culture and surgical site infection (P= 0.43). Conclusion: There was no apparent association between positive intraoperative irradiated soft tissue allograft cultures and surgical site infection in reconstructive knee surgery.Item Specific, Sensitive, and Stable Reporting of Human Mesenchymal Stromal Cell Chondrogenesis(2019) De la Vega, Rodolfo E.; Scheu, Maximiliano; Brown, Lennart A.; Evans, Christopher H.; Ferreira, Elisabeth; Porter, Ryan M.Chondrogenesis is critical to the development and repair of not only articular cartilage but also bone. Preclinical studies suggest that defects in both tissues can be repaired using culture-expanded chondroprogenitor cells, such as mesenchymal stem/stromal cells (MSCs), but directing efficient chondrogenesis by candidate cell populations is an ongoing bottleneck to their clinical application. The goal of this study was to describe a method for the molecular reporting of chondrogenic activity by primary stem/progenitor cells that can complement more labor-intensive destructive measures. A chondrogenesis-responsive promoter was generated, consisting of four repeats of a SOX9-binding enhancer sequence from the first intron of COL2A1 positioned upstream of the core COL2A1 promoter. This promoter was inserted into a lentiviral expression plasmid containing reporter genes copepod green fluorescent protein (copGFP) and firefly luciferase (fLuc), and the resulting lentiviral vector (LV) was used to transduce human MSCs derived from intramedullary reamings. To determine the specificity and stability of reporter expression, MSCs were differentiated in pellet culture for up to 4 weeks. To assess the sensitivity of reporter detection in vivo, undifferentiated and predifferentiated MSC pellets were implanted into osteochondral defects made in immune-suppressed rats. Chondrogenic differentiation of LV-transduced MSCs in pellet culture led to a strong upregulation of both copGFP and fLuc. Robust reporter activity was achieved using LV doses that did not compromise MSC chondrogenesis. Specific reporter induction was sustained over several passages post-transduction. Reporter expression levels were dependent on both pellet culture duration and TGF-β1 dose. When predifferentiated pellets were implanted into rat osteochondral defects, reporter activity was initially diminished but recovered over the following 2 weeks, suggesting acute postsurgical inflammation suppressed reporter expression. This hypothesis was supported by potent cytokine inhibition of reporter levels and glycosaminoglycan deposition within additional pellets in vitro. When combined with lentiviral transgene integration, the COL2A1-based promoter allowed specific, sensitive, and stable reporting of MSC chondrogenic activity. This promoter can be used with the extensive selection of reporter vectors now available to study different chondroprogenitor cells with promise for cartilage and bone tissue engineering and regenerative medicine.Item Varus mechanism is associated with high incidence of popliteal artery lesions in multiligament knee injuries(2020) Scheu, Maximiliano; Espinoza, Gonzalo F.; Mellado, Carolina A.; Díaz, Pedro A.; Garín, Alan F.; O’Connell, Luis A.Purpose This study aims to identify multiple ligament knee injury patterns that possess a high-risk of vascular lesion. Methods We retrospectively compared torn ligament patterns and the presence of vascular lesions confirmed by magnetic resonance imaging and computed tomography angiography from 122 consecutive patients with diagnoses of multiple ligament knee injury made at the emergency department between January 2012 and December 2017. Patients were not eligible if they had an ipsilateral lower extremity lesion (dislocations or fractures at another level), initial evaluation at another hospital, or follow-up for less than 12 months. The primary outcomes were the comparison between the imaging findings of torn structures patterns and the presence of a vascular lesion. Results We identified 48 eligible patients (50 knees) with multiligamentary knee lesions, of whom eight had popliteal artery damage, yielding an incidence of 16%. Our clinical examination detected six of these patients that were classified, according to the Schenck system, as KD-IIIL (6 knees) and KD-IIIM(2 knees). The odds of having a popliteal artery injury is 4.69 to 1 with a KD-IIIL injury that with any other type of injury on that classification (95% CI 0.960–22.98). Conclusions This data suggests that varus forces causing enough energy to produce a KD-IIIL lesion possess a higher popliteal artery injury risk, making recommendable a thorough examination of the vascular integrity when diagnosing a KD-IIIL lesion.