Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic ...and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold's shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved.
Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the
cardiac ...microenvironment and our ability to replicate those parameters
are resulting in the development of increasingly sophisticated models of engineered cardiac tissues (ECT). This review examines some of the most relevant parameters that may be applied in culture leading to higher fidelity cardiac tissue models. These include the biochemical composition of culture media and cardiac lineage specification, co-culture conditions, electrical and mechanical stimulation, and the application of hydrogels, various biomaterials, and scaffolds. The review will also summarize some of the recent functional human tissue models that have been developed for
and
applications. Ultimately, the creation of sophisticated ECT that replicate native structure and function will be instrumental in advancing cell-based therapeutics and in providing advanced models for drug discovery and testing.
Integrins are a family of heterodimeric proteins expressed by cardiac fibroblasts and cardiomyocytes that provide critical adhesive and signaling functions through their interactions with the ...extracellular matrix (ECM) and the actin cytoskeleton. These adhesive processes are important for paracrine signaling, ECM homeostasis and for the intercellular interactions that impact cardiac cell biology and pathophysiological adaptation in disease. Despite considerable progress, our understanding of the interplay between cardiac cells, the ECM and integrins remains largely elusive. In this review, we examine the role of integrins in adhesive and signaling functions, and how these functions enable communication between cardiac fibroblasts, cardiomyocytes and the ECM. These processes strongly influence cardiac development and, later, the progression into cardiac disease. An improved understanding of this multi-dimensional system in cardiac tissues is needed to decipher the biological, spatiotemporal and mechanical cues that regulate cardiac health and the manifestation of cardiac disease. Greater insight into integrin function in cardiac tissues may also suggest new treatments for the prevention of heart failure.
Excessive cardiac interstitial fibrosis impairs normal cardiac function. We have shown that the α11β1 (α11) integrin mediates fibrotic responses to glycated collagen in rat myocardium by a pathway ...involving transforming growth factor-β. Little is known of the role of the α11 integrin in the developing mammalian heart. Therefore, we examined the impact of deletion of the α11 integrin in wild-type mice and in mice treated with streptozotocin (STZ) to elucidate the role of the α11 integrin in normal cardiac homeostasis and in the pathogenesis of diabetes-related fibrosis. As anticipated, cardiac fibrosis was reduced in α11 integrin knockout mice (α11(-/-); C57BL/6 background) treated with STZ compared with STZ-treated wild-type mice (P < 0.05). Unexpectedly, diastolic function was impaired in both vehicle and STZ-treated α11(-/-) mice, as shown by the decreased minimum rate of pressure change and prolonged time constant of relaxation in association with increased end-diastolic pressure (all P < 0.05 compared with wild-type mice). Accordingly, we examined the phenotype of untreated α11(-/-) mice, which demonstrated a reduced cardiomyocyte cross-sectional cell area and myofibril thickness (all P < 0.05 compared with wild-type mice) and impaired myofibril arrangement. Immunostaining for desmin and connexin 43 showed abnormal intermediate filament organization at intercalated disks and impaired gap-junction development. Overall, deletion of the α11 integrin attenuates cardiac fibrosis in the mammalian mouse heart and reduces ECM formation as a result of diabetes. Furthermore, α11 integrin deletion impairs cardiac function and alters cardiomyocyte morphology. These findings shed further light on the poorly understood interaction between the fibroblast-cardiomyocyte and the ECM.
Excessive cardiac interstitial fibrosis impairs normal cardiac function. We have shown that the a11 beta 1 (a11) integrin mediates fibrotic responses to glycated collagen in rat myocardium by a ...pathway involving transforming growth factor- beta . Little is known of the role of the a11 integrin in the developing mammalian heart. Therefore, we examined the impact of deletion of the a11 integrin in wild-type mice and in mice treated with streptozotocin (STZ) to elucidate the role of the a11 integrin in normal cardiac homeostasis and in the pathogenesis of diabetes-related fibrosis. As anticipated, cardiac fibrosis was reduced in a11 integrin knockout mice (a11 super( -/-); C57BL/6 background) treated with STZ compared with STZ-treated wild-type mice (P < 0.05). Unexpectedly, diastolic function was impaired in both vehicle and STZ-treated a11 super( -/-) mice, as shown by the decreased minimum rate of pressure change and prolonged time constant of relaxation in association with increased end-diastolic pressure (all P < 0.05 compared with wild-type mice). Accordingly, we examined the phenotype of untreated a11 super( -/-) mice, which demonstrated a reduced cardiomyocyte cross-sectional cell area and myofibril thickness (all P < 0.05 compared with wild-type mice) and impaired myofibril arrangement. Immunostaining for desmin and connexin 43 showed abnormal intermediate filament organization at intercalated disks and impaired gap-junction development. Overall, deletion of the a11 integrin attenuates cardiac fibrosis in the mammalian mouse heart and reduces ECM formation as a result of diabetes. Furthermore, a11 integrin deletion impairs cardiac function and alters cardiomyocyte morphology. These findings shed further light on the poorly understood interaction between the fibroblast-cardiomyocyte and the ECM.
Emerging Updates on the Posterior Cruciate Ligament LaPrade, Christopher M.; Civitarese, David M.; Rasmussen, Matthew T. ...
The American journal of sports medicine,
12/2015, Letnik:
43, Številka:
12
Journal Article
Recenzirano
The posterior cruciate ligament (PCL) is recognized as an essential stabilizer of the knee. However, the complexity of the ligament has generated controversy about its definitive role and the ...recommended treatment after injury. A proper understanding of the functional role of the PCL is necessary to minimize residual instability, osteoarthritic progression, and failure of additional concomitant ligament graft reconstructions or meniscal repairs after treatment. Recent anatomic and biomechanical studies have elucidated the surgically relevant quantitative anatomy and confirmed the codominant role of the anterolateral and posteromedial bundles of the PCL. Although nonoperative treatment has historically been the initial treatment of choice for isolated PCL injury, possibly biased by the historically poorer objective outcomes postoperatively compared with anterior cruciate ligament reconstructions, surgical intervention has been increasingly used for isolated and combined PCL injuries. Recent studies have more clearly elucidated the biomechanical and clinical effects after PCL tears and resultant treatments. This article presents a thorough review of updates on the clinically relevant anatomy, epidemiology, biomechanical function, diagnosis, and current treatments for the PCL, with an emphasis on the emerging clinical and biomechanical evidence regarding each of the treatment choices for PCL reconstruction surgery. It is recommended that future outcomes studies use PCL stress radiographs to determine objective outcomes and that evidence level 1 and 2 studies be performed to assess outcomes between transtibial and tibial inlay reconstructions and also between single- and double-bundle PCL reconstructions.
Background:
The clinical importance of the meniscal posterior root attachments has been recently reported by both biomechanical and clinical studies. Although several studies have been performed to ...evaluate surgical techniques, there have been few studies on the quantitative arthroscopically pertinent anatomy of the posterior meniscal root attachments.
Hypothesis:
The posterior root attachments of the medial and lateral menisci are consistent among specimens, and repeatable quantitative measurements using arthroscopically pertinent landmarks are achievable.
Study Design:
Descriptive laboratory study.
Methods:
Twelve nonpaired, fresh-frozen cadaveric knees were used. The positions of the posterior root attachments of the medial and lateral menisci were identified, and 3-dimensional measurements to arthroscopically pertinent landmarks were performed using a coordinate measuring system.
Results:
The direct distance (±standard error of the mean) between the medial tibial eminence apex and the medial meniscus posterior root attachment center was 11.5 (±0.9) mm. When split into directional components along the knee’s main axes, the medial meniscus posterior root attachment center was 9.6 (±0.8) mm posterior and 0.7 (±0.4) mm lateral along the bony surface from the medial tibial eminence apex. It was located 3.5 (±0.4) mm lateral from the medial articular cartilage inflection point and directly 8.2 (±0.7) mm from the nearest tibial attachment margin of the posterior cruciate ligament. The direct distance between the lateral tibial eminence apex and the lateral meniscus posterior root attachment center was 5.3 (±0.3) mm. When it was split into directional components using the knee’s main axes, the lateral meniscus posterior root attachment center was 4.2 (±0.4) mm medial and 1.5 (±0.7) mm posterior from the lateral tibial eminence apex. The lateral meniscus posterior root attachment center was located 4.3 (±0.5) mm medial from the nearest articular cartilage margin and directly 12.7 (±1.1) mm from the nearest margin of the tibial attachment of the posterior cruciate ligament.
Conclusion:
This quantitative study reproducibly identified the posterior root attachment centers of the medial and lateral menisci in relation to arthroscopically pertinent landmarks and guidelines.
Clinical Relevance:
These data can be directly applied to assist in anatomic meniscal root repairs.
Purpose To systematically review meniscal radial tear repair procedures and compare the techniques, outcomes, and complications. Methods Studies were identified through a systematic review of the ...literature using the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (1980-2014), Medline (1980-2014), and Embase. Inclusion criteria included a minimum follow-up of 24 months, English language, and publications from 1980 or later. Exclusion criteria were surgical techniques not reporting follow-up, biomechanical studies, cadaver/anatomic studies, and non-radial tear meniscal repair procedures. Meniscal radial repair, meniscal radial tear, meniscal radial tear repair, radial repair and radial tear were used as search terms. Results A total of 6 studies (55 patients) met the inclusion criteria. The mean duration of follow-up ranged from 24 to 71 months. Of the 6 studies, 5 reported radial tears to the lateral meniscus and 1 study reported cases of both medial and lateral meniscal radial tears. Two studies reported different inside-out repair techniques, 2 studies reported the use of an all-inside anchor-based repair system, 1 study reported an all-inside repair technique with absorbable sutures, and 1 study reported an inside-out repair with fibrin clots. Average postoperative Lysholm scores were reported in all 6 studies and ranged from 86.9 to 95.6. Average postoperative Tegner activity scores were reported in 4 studies and ranged from 1 to 6.7. The majority of studies concluded that their techniques produced satisfactory healing of the radial tear, without serious subsequent complications. Conclusions Radial repair techniques differed among studies; however, postoperative subjective outcomes revealed patient improvement with repairing radial tears. With the increasing concern of long-term osteoarthritis after meniscectomy, meniscal preservation with repair of radial tears results in improved short-term clinical outcomes; however, long-term outcomes remain unknown. Level of Evidence Level IV, systematic review of level IV studies.
Excessive cardiac interstitial fibrosis impairs normal cardiac function. We have shown that the a11β1 (a11) integrin mediates fibrotic responses to glycated collagen in rat myocardium by a pathway ...involving transforming growth factor-β. Little is known of the role of the a11 integrin in the developing mammalian heart. Therefore, we examined the impact of deletion of the a11 integrin in wild-type mice and in mice treated with streptozotocin (STZ) to elucidate the role of the a11 integrin in normal cardiac homeostasis and in the pathogenesis of diabetes-related fibrosis. As anticipated, cardiac fibrosis was reduced in a11 integrin knockout mice (a11^sup -/-^; C57BL/6 background) treated with STZ compared with STZ-treated wild-type mice (P < 0.05). Unexpectedly, diastolic function was impaired in both vehicle and STZ-treated a11^sup -/-^ mice, as shown by the decreased minimum rate of pressure change and prolonged time constant of relaxation in association with increased end-diastolic pressure (all P < 0.05 compared with wild-type mice). Accordingly, we examined the phenotype of untreated a11^sup -/-^ mice, which demonstrated a reduced cardiomyocyte cross-sectional cell area and myofibril thickness (all P < 0.05 compared with wild-type mice) and impaired myofibril arrangement. Immunostaining for desmin and connexin 43 showed abnormal intermediate filament organization at intercalated disks and impaired gap-junction development. Overall, deletion of the a11 integrin attenuates cardiac fibrosis in the mammalian mouse heart and reduces ECM formation as a result of diabetes. Furthermore, a11 integrin deletion impairs cardiac function and alters cardiomyocyte morphology. These findings shed further light on the poorly understood interaction between the fibroblast-cardiomyocyte and the ECM.
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