The Experts below are selected from a list of 7161 Experts worldwide ranked by ideXlab platform
Alan J Nixon - One of the best experts on this subject based on the ideXlab platform.
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label free analysis of physiological hyaluronan size distribution with a solid state nanopore sensor
Nature Communications, 2018Co-Authors: Felipe Rivas, Alan J Nixon, Osama K Zahid, Heidi L Reesink, Bridgette T Peal, Paul L Deangelis, Aleksander Skardal, Elaheh Rahbar, Adam R HallAbstract:Hyaluronan (or hyaluronic acid, HA) is a ubiquitous molecule that plays critical roles in numerous physiological functions in vivo, including tissue hydration, inflammation, and joint lubrication. Both the abundance and size distribution of HA in biological fluids are recognized as robust indicators of various pathologies and disease progressions. However, such analyses remain challenging because conventional methods are not sufficiently sensitive, have limited dynamic range, and/or are only semi-quantitative. Here we demonstrate label-free detection and molecular weight discrimination of HA with a solid-state nanopore sensor. We first employ synthetic HA polymers to validate the measurement approach and then use the platform to determine the size distribution of as little as 10 ng of HA extracted directly from synovial fluid in an Equine Model of osteoarthritis. Our results establish a quantitative method for assessment of a significant molecular biomarker that bridges a gap in the current state of the art.
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label free analysis of physiological hyaluronan size distribution with a solid state nanopore sensor
Nature Communications, 2018Co-Authors: Felipe Rivas, Alan J Nixon, Osama K Zahid, Heidi L Reesink, Bridgette T Peal, Paul L Deangelis, Aleksander Skardal, Elaheh Rahbar, Adam R HallAbstract:Hyaluronan (or hyaluronic acid, HA) is a ubiquitous molecule that plays critical roles in numerous physiological functions in vivo, including tissue hydration, inflammation, and joint lubrication. Both the abundance and size distribution of HA in biological fluids are recognized as robust indicators of various pathologies and disease progressions. However, such analyses remain challenging because conventional methods are not sufficiently sensitive, have limited dynamic range, and/or are only semi-quantitative. Here we demonstrate label-free detection and molecular weight discrimination of HA with a solid-state nanopore sensor. We first employ synthetic HA polymers to validate the measurement approach and then use the platform to determine the size distribution of as little as 10 ng of HA extracted directly from synovial fluid in an Equine Model of osteoarthritis. Our results establish a quantitative method for assessment of a significant molecular biomarker that bridges a gap in the current state of the art. Involved in various diseases, hyaluronic acid is an important indicator of pathophysiology. Here, the authors report on a solid-state nanopore for the detection of the molecular weight and abundance of hyaluronic acid and demonstrate the system by studying an Equine Model of osteoarthritis
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matrix induced autologous chondrocyte implantation maci using a cell seeded collagen membrane improves cartilage healing in the Equine Model
Journal of Bone and Joint Surgery American Volume, 2017Co-Authors: Alan J Nixon, Michael S Scimeca, N Moran, Laila Begum, Holly D Sparks, Sean P Mcdonough, Gloria MatthewsAbstract:Background:Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has i
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a chondrocyte infiltrated collagen type i iii membrane maci implant improves cartilage healing in the Equine patellofemoral joint Model
Osteoarthritis and Cartilage, 2015Co-Authors: Alan J Nixon, E Rickey, T Butler, Michael S Scimeca, N Moran, Gloria MatthewsAbstract:Summary Autologous chondrocyte implantation (ACI) has improved outcome in long-term studies of joint repair in man. However, ACI requires sutured periosteal flaps to secure the cells, which precludes minimally-invasive implantation, and introduces complications with arthrofibrosis and graft hypertrophy. This study evaluated ACI on a collagen type I/III scaffold (matrix-induced autologous chondrocyte implantation; MACI ® ) in critical sized defects in the Equine Model. Methods Chondrocytes were isolated from horses, expanded and seeded onto a collagen I/III membrane (ACI-Maix™) and implanted into one of two 15-mm defects in the femoral trochlear ridge of six horses. Control defects remained empty as ungrafted debrided defects. The animals were examined daily, scored by second look arthroscopy at 12 weeks, and necropsy examination 6 months after implantation. Reaction to the implant was determined by lameness, and synovial fluid constituents and synovial membrane histology. Cartilage healing was assessed by arthroscopic scores, gross assessment, repair tissue histology and immunohistochemistry, cartilage glycosaminoglycan (GAG) and DNA assay, and mechanical testing. Results MACI ® implanted defects had improved arthroscopic second-look, gross healing, and composite histologic scores, compared to spontaneously healing empty defects. Cartilage GAG and DNA content in the defects repaired by MACI implant were significantly improved compared to controls. Mechanical properties were improved but remained inferior to normal cartilage. There was minimal evidence of reaction to the implant in the synovial fluid, synovial membrane, subchondral bone, or cartilage. Conclusions The MACI ® implant appeared to improve cartilage healing in a critical sized defect in the Equine Model evaluated over 6 months.
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implantation of raav5 igf i transduced autologous chondrocytes improves cartilage repair in full thickness defects in the Equine Model
Molecular Therapy, 2015Co-Authors: Kyla F Ortved, Hussni O Mohammed, Laila Begum, Alan J NixonAbstract:Cartilage injury often precipitates osteoarthritis which has driven research to bolster repair in cartilage impact damage. Autologous chondrocytes transduced with rAAV5-IGF-I were evaluated in chondral defects in a well-established large animal Model. Cartilage was harvested from the talus of 24 horses; chondrocytes were isolated and stored frozen. Twenty million cells were cultured and transduced with 105 AAV vg/cell prior to implantation. Chondrocytes from eight horses were transduced with rAAV5-IGF-I, chondrocytes from eight horses with rAAV5-GFP, and chondrocytes from eight horses were not transduced. A 15 mm full-thickness chondral defect was created arthroscopically in the lateral trochlear ridge of the femur in both femoropatellar joints. Treated defects were filled with naive or gene-enhanced chondrocytes, in fibrin vehicle. Control defects in the opposite limb received fibrin alone. rAAV5-IGF-I transduced chondrocytes resulted in significantly better healing at 8 week arthroscopy and 8 month necropsy examination when compared to controls. At 8 months, defects implanted with cells expressing IGF-I had better histological scores compared to control defects and defects repaired with naive chondrocytes. This included increased chondrocyte predominance and collagen type II, both features of hyaline-like repair tissue. The Equine Model closely approximates human cartilage healing, indicating AAV-mediated genetic modification of chondrocytes may be clinically beneficial to humans.
Gloria Matthews - One of the best experts on this subject based on the ideXlab platform.
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matrix induced autologous chondrocyte implantation maci using a cell seeded collagen membrane improves cartilage healing in the Equine Model
Journal of Bone and Joint Surgery American Volume, 2017Co-Authors: Alan J Nixon, Michael S Scimeca, N Moran, Laila Begum, Holly D Sparks, Sean P Mcdonough, Gloria MatthewsAbstract:Background:Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has i
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mechanical characterization of matrix induced autologous chondrocyte implantation maci grafts in an Equine Model at 53 weeks
Journal of Biomechanics, 2015Co-Authors: Darvi J Griffi, Gloria Matthews, Holly D Sparks, Edward D Onnevie, Devi J Lachowsky, N Mora, Ala J Nixo, Itai Cohe, Lawrence J OnassaAbstract:Abstract There has been much interest in using autologous chondrocytes in combination with scaffold materials to aid in cartilage repair. In the present study, a total of 27 animals were used to compare the performance of matrix-assisted chondrocyte implantation (MACI®) using a collagen sponge as a chondrocyte delivery vehicle, the sponge membrane alone, and empty controls. A total of three distinct types of mechanical analyses were performed on repaired cartilage harvested from horses after 53 weeks of implantation: (1) compressive behavior of samples to measure aggregate modulus (HA) and hydraulic permeability ( k ) in confined compression; (2) local and global shear modulus using confocal strain mapping; and (3) boundary friction coefficient using a custom-built tribometer. Cartilage defects receiving MACI® implants had equilibrium modulus values that were 70% of normal cartilage, and were not statistically different than normal tissue. Defects filled with Maix™ membrane alone or left empty were only 46% and 51–63% of control, respectively. The shear modulus of tissue from all groups of cartilage defects were between 4 and 10 times lower than control tissue, and range from 0.2 to 0.4 MPa. The average values of boundary mode friction coefficients of control tissue from all groups ranged from 0.42 to 0.52. This study represents an extensive characterization of the mechanical performance of the MACI® grafts implant in a large animal Model at 53 weeks. Collectively, these data demonstrate a range of implant performance, revealing similar compressive and frictional properties to native tissue, with inferior shear properties.
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a chondrocyte infiltrated collagen type i iii membrane maci implant improves cartilage healing in the Equine patellofemoral joint Model
Osteoarthritis and Cartilage, 2015Co-Authors: Alan J Nixon, E Rickey, T Butler, Michael S Scimeca, N Moran, Gloria MatthewsAbstract:Summary Autologous chondrocyte implantation (ACI) has improved outcome in long-term studies of joint repair in man. However, ACI requires sutured periosteal flaps to secure the cells, which precludes minimally-invasive implantation, and introduces complications with arthrofibrosis and graft hypertrophy. This study evaluated ACI on a collagen type I/III scaffold (matrix-induced autologous chondrocyte implantation; MACI ® ) in critical sized defects in the Equine Model. Methods Chondrocytes were isolated from horses, expanded and seeded onto a collagen I/III membrane (ACI-Maix™) and implanted into one of two 15-mm defects in the femoral trochlear ridge of six horses. Control defects remained empty as ungrafted debrided defects. The animals were examined daily, scored by second look arthroscopy at 12 weeks, and necropsy examination 6 months after implantation. Reaction to the implant was determined by lameness, and synovial fluid constituents and synovial membrane histology. Cartilage healing was assessed by arthroscopic scores, gross assessment, repair tissue histology and immunohistochemistry, cartilage glycosaminoglycan (GAG) and DNA assay, and mechanical testing. Results MACI ® implanted defects had improved arthroscopic second-look, gross healing, and composite histologic scores, compared to spontaneously healing empty defects. Cartilage GAG and DNA content in the defects repaired by MACI implant were significantly improved compared to controls. Mechanical properties were improved but remained inferior to normal cartilage. There was minimal evidence of reaction to the implant in the synovial fluid, synovial membrane, subchondral bone, or cartilage. Conclusions The MACI ® implant appeared to improve cartilage healing in a critical sized defect in the Equine Model evaluated over 6 months.
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autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full and partial thickness cartilage defects in an Equine Model
Journal of Orthopaedic Research, 2011Co-Authors: Alan J Nixon, Laila Begum, Hussni O Mohammed, Barbara A Huibregtse, Michael Ocallaghan, Gloria MatthewsAbstract:Autologous chondrocyte implantation (ACI) has been used clinically for over 15 years and yet definitive evidence of chondrocyte persistence and direct impact on cartilage repair in full-thickness lesions is scant and no data are available on ACI in partial-thickness defects in any animal Model. This study assessed the effect of chondrocytes secured using periosteal overlay in partial- and full-thickness cartilage defects in the Equine Model. Paired cartilage defects 15 mm in diameter were made in the patellofemoral joint of 16 horse and repaired with ACI or periosteal flap alone. Response was assessed at 8 weeks by clinical, microradiographic, and histologic appearance, and by collagen type II immunohistochemistry, and proteoglycan and DNA quantification. ACI improved histologic scores in partial- and full-thickness cartilage defects, including defect filling, attachment to the underlying subchondral bone, and presence of residual chondrocyte accumulations. For partial-thickness defects chondrocyte predominance, collagen type II content, and toluidine stained matrix were enhanced, and attachment to the surrounding cartilage improved. DNA and PG content of grafted partial-thickness defects was improved by chondrocyte implantation. Periosteal patches alone did not induce cartilage repair. This study indicated implantation of chondrocytes to cartilage defects improved healing with a combination of persisting chondrocyte regions, enhanced collagen type II formation, and better overall cartilage healing scores. Use of ACI in the more challenging partial-thickness defects also improved histologic indices and biochemical content. The Equine Model of cartilage healing closely resembles cartilage repair in man, and results of this study confirm cell persistence and improved early cartilage healing events after ACI. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1121–1130, 2011
Laila Begum - One of the best experts on this subject based on the ideXlab platform.
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matrix induced autologous chondrocyte implantation maci using a cell seeded collagen membrane improves cartilage healing in the Equine Model
Journal of Bone and Joint Surgery American Volume, 2017Co-Authors: Alan J Nixon, Michael S Scimeca, N Moran, Laila Begum, Holly D Sparks, Sean P Mcdonough, Gloria MatthewsAbstract:Background:Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has i
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implantation of raav5 igf i transduced autologous chondrocytes improves cartilage repair in full thickness defects in the Equine Model
Molecular Therapy, 2015Co-Authors: Kyla F Ortved, Hussni O Mohammed, Laila Begum, Alan J NixonAbstract:Cartilage injury often precipitates osteoarthritis which has driven research to bolster repair in cartilage impact damage. Autologous chondrocytes transduced with rAAV5-IGF-I were evaluated in chondral defects in a well-established large animal Model. Cartilage was harvested from the talus of 24 horses; chondrocytes were isolated and stored frozen. Twenty million cells were cultured and transduced with 105 AAV vg/cell prior to implantation. Chondrocytes from eight horses were transduced with rAAV5-IGF-I, chondrocytes from eight horses with rAAV5-GFP, and chondrocytes from eight horses were not transduced. A 15 mm full-thickness chondral defect was created arthroscopically in the lateral trochlear ridge of the femur in both femoropatellar joints. Treated defects were filled with naive or gene-enhanced chondrocytes, in fibrin vehicle. Control defects in the opposite limb received fibrin alone. rAAV5-IGF-I transduced chondrocytes resulted in significantly better healing at 8 week arthroscopy and 8 month necropsy examination when compared to controls. At 8 months, defects implanted with cells expressing IGF-I had better histological scores compared to control defects and defects repaired with naive chondrocytes. This included increased chondrocyte predominance and collagen type II, both features of hyaline-like repair tissue. The Equine Model closely approximates human cartilage healing, indicating AAV-mediated genetic modification of chondrocytes may be clinically beneficial to humans.
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autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full and partial thickness cartilage defects in an Equine Model
Journal of Orthopaedic Research, 2011Co-Authors: Alan J Nixon, Laila Begum, Hussni O Mohammed, Barbara A Huibregtse, Michael Ocallaghan, Gloria MatthewsAbstract:Autologous chondrocyte implantation (ACI) has been used clinically for over 15 years and yet definitive evidence of chondrocyte persistence and direct impact on cartilage repair in full-thickness lesions is scant and no data are available on ACI in partial-thickness defects in any animal Model. This study assessed the effect of chondrocytes secured using periosteal overlay in partial- and full-thickness cartilage defects in the Equine Model. Paired cartilage defects 15 mm in diameter were made in the patellofemoral joint of 16 horse and repaired with ACI or periosteal flap alone. Response was assessed at 8 weeks by clinical, microradiographic, and histologic appearance, and by collagen type II immunohistochemistry, and proteoglycan and DNA quantification. ACI improved histologic scores in partial- and full-thickness cartilage defects, including defect filling, attachment to the underlying subchondral bone, and presence of residual chondrocyte accumulations. For partial-thickness defects chondrocyte predominance, collagen type II content, and toluidine stained matrix were enhanced, and attachment to the surrounding cartilage improved. DNA and PG content of grafted partial-thickness defects was improved by chondrocyte implantation. Periosteal patches alone did not induce cartilage repair. This study indicated implantation of chondrocytes to cartilage defects improved healing with a combination of persisting chondrocyte regions, enhanced collagen type II formation, and better overall cartilage healing scores. Use of ACI in the more challenging partial-thickness defects also improved histologic indices and biochemical content. The Equine Model of cartilage healing closely resembles cartilage repair in man, and results of this study confirm cell persistence and improved early cartilage healing events after ACI. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1121–1130, 2011
Holly D Sparks - One of the best experts on this subject based on the ideXlab platform.
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biomechanics of wound healing in an Equine limb Model effect of location and treatment with a peptide modified collagen chitosan hydrogel
ACS Biomaterials Science & Engineering, 2021Co-Authors: Holly D Sparks, Taisiya Sigaeva, Samar Tarraf, Serena Mandla, Hannah Pope, Olivia Hee, Elena S Di Martino, Jeff BiernaskieAbstract:The Equine distal limb wound healing Model, characterized by delayed re-epithelialization and a fibroproliferative response to wounding similar to that observed in humans, is a valuable tool for the study of biomaterials poised for translation into both the veterinary and human medical markets. In the current study, we developed a novel method of biaxial biomechanical testing to assess the functional outcomes of healed wounds in a modified Equine Model and discovered significant functional and structural differences in both unwounded and injured skin at different locations on the distal limb that must be considered when using this Model in future work. Namely, the medial skin was thicker and displayed earlier collagen engagement, medial wounds experienced a greater proportion of wound contraction during closure, and proximal wounds produced significantly more exuberant granulation tissue. Using this new knowledge of the Equine Model of aberrant wound healing, we then investigated the effect of a peptide-modified collagen-chitosan hydrogel on wound healing. Here, we found that a single treatment with the QHREDGS (glutamine-histidine-arginine-glutamic acid-aspartic acid-glycine-serine) peptide-modified hydrogel (Q-peptide hydrogel) resulted in a higher rate of wound closure and was able to modulate the biomechanical function toward a more compliant healed tissue without observable negative effects. Thus, we conclude that the use of a Q-peptide hydrogel provides a safe and effective means of improving the rate and quality of wound healing in a large animal Model.
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matrix induced autologous chondrocyte implantation maci using a cell seeded collagen membrane improves cartilage healing in the Equine Model
Journal of Bone and Joint Surgery American Volume, 2017Co-Authors: Alan J Nixon, Michael S Scimeca, N Moran, Laila Begum, Holly D Sparks, Sean P Mcdonough, Gloria MatthewsAbstract:Background:Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has i
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mechanical characterization of matrix induced autologous chondrocyte implantation maci grafts in an Equine Model at 53 weeks
Journal of Biomechanics, 2015Co-Authors: Darvi J Griffi, Gloria Matthews, Holly D Sparks, Edward D Onnevie, Devi J Lachowsky, N Mora, Ala J Nixo, Itai Cohe, Lawrence J OnassaAbstract:Abstract There has been much interest in using autologous chondrocytes in combination with scaffold materials to aid in cartilage repair. In the present study, a total of 27 animals were used to compare the performance of matrix-assisted chondrocyte implantation (MACI®) using a collagen sponge as a chondrocyte delivery vehicle, the sponge membrane alone, and empty controls. A total of three distinct types of mechanical analyses were performed on repaired cartilage harvested from horses after 53 weeks of implantation: (1) compressive behavior of samples to measure aggregate modulus (HA) and hydraulic permeability ( k ) in confined compression; (2) local and global shear modulus using confocal strain mapping; and (3) boundary friction coefficient using a custom-built tribometer. Cartilage defects receiving MACI® implants had equilibrium modulus values that were 70% of normal cartilage, and were not statistically different than normal tissue. Defects filled with Maix™ membrane alone or left empty were only 46% and 51–63% of control, respectively. The shear modulus of tissue from all groups of cartilage defects were between 4 and 10 times lower than control tissue, and range from 0.2 to 0.4 MPa. The average values of boundary mode friction coefficients of control tissue from all groups ranged from 0.42 to 0.52. This study represents an extensive characterization of the mechanical performance of the MACI® grafts implant in a large animal Model at 53 weeks. Collectively, these data demonstrate a range of implant performance, revealing similar compressive and frictional properties to native tissue, with inferior shear properties.
N Moran - One of the best experts on this subject based on the ideXlab platform.
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matrix induced autologous chondrocyte implantation maci using a cell seeded collagen membrane improves cartilage healing in the Equine Model
Journal of Bone and Joint Surgery American Volume, 2017Co-Authors: Alan J Nixon, Michael S Scimeca, N Moran, Laila Begum, Holly D Sparks, Sean P Mcdonough, Gloria MatthewsAbstract:Background:Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has i
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a chondrocyte infiltrated collagen type i iii membrane maci implant improves cartilage healing in the Equine patellofemoral joint Model
Osteoarthritis and Cartilage, 2015Co-Authors: Alan J Nixon, E Rickey, T Butler, Michael S Scimeca, N Moran, Gloria MatthewsAbstract:Summary Autologous chondrocyte implantation (ACI) has improved outcome in long-term studies of joint repair in man. However, ACI requires sutured periosteal flaps to secure the cells, which precludes minimally-invasive implantation, and introduces complications with arthrofibrosis and graft hypertrophy. This study evaluated ACI on a collagen type I/III scaffold (matrix-induced autologous chondrocyte implantation; MACI ® ) in critical sized defects in the Equine Model. Methods Chondrocytes were isolated from horses, expanded and seeded onto a collagen I/III membrane (ACI-Maix™) and implanted into one of two 15-mm defects in the femoral trochlear ridge of six horses. Control defects remained empty as ungrafted debrided defects. The animals were examined daily, scored by second look arthroscopy at 12 weeks, and necropsy examination 6 months after implantation. Reaction to the implant was determined by lameness, and synovial fluid constituents and synovial membrane histology. Cartilage healing was assessed by arthroscopic scores, gross assessment, repair tissue histology and immunohistochemistry, cartilage glycosaminoglycan (GAG) and DNA assay, and mechanical testing. Results MACI ® implanted defects had improved arthroscopic second-look, gross healing, and composite histologic scores, compared to spontaneously healing empty defects. Cartilage GAG and DNA content in the defects repaired by MACI implant were significantly improved compared to controls. Mechanical properties were improved but remained inferior to normal cartilage. There was minimal evidence of reaction to the implant in the synovial fluid, synovial membrane, subchondral bone, or cartilage. Conclusions The MACI ® implant appeared to improve cartilage healing in a critical sized defect in the Equine Model evaluated over 6 months.