Search

Your search keyword '"Mauck, Robert L."' showing total 428 results
Start Over Author "Mauck, Robert L." Search Limiters Full Text
428 results on '"Mauck, Robert L."'

9. Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

Author

Smith, Lachlan J, Silverman, Lara, Sakai, Daisuke, Le Maitre, Christine L, Mauck, Robert L, Malhotra, Neil R, Lotz, Jeffrey C, and Buckley, Conor T

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pain Research, Regenerative Medicine, Neurosciences, Back Pain, Chronic Pain, 5.2 Cellular and gene therapies, Musculoskeletal, biological therapies, biomaterials, preclinical models, stem cells
Abstract

Intervertebral disc degeneration is strongly associated with chronic low back pain, a leading cause of disability worldwide. Current back pain treatment approaches (both surgical and conservative) are limited to addressing symptoms, not necessarily the root cause. Not surprisingly therefore, long-term efficacy of most approaches is poor. Cell-based disc regeneration strategies have shown promise in preclinical studies, and represent a relatively low-risk, low-cost, and durable therapeutic approach suitable for a potentially large patient population, thus making them attractive from both clinical and commercial standpoints. Despite such promise, no such therapies have been broadly adopted clinically. In this perspective we highlight primary obstacles and provide recommendations to help accelerate successful clinical translation of cell-based disc regeneration therapies. The key areas addressed include: (a) Optimizing cell sources and delivery techniques; (b) Minimizing potential risks to patients; (c) Selecting physiologically and clinically relevant efficacy metrics; (d) Maximizing commercial potential; and (e) Recognizing the importance of multidisciplinary collaborations and engaging with clinicians from inception through to clinical trials.

Published
2018

30. Developmental morphogens direct human induced pluripotent stem cells toward an annulus fibrosus‐like cell phenotype.

Author

Peredo, Ana P., Tsinman, Tonia K., Bonnevie, Edward D., Jiang, Xi, Smith, Harvey E., Gullbrand, Sarah E., Dyment, Nathaniel A., and Mauck, Robert L.

Subjects
PLURIPOTENT stem cells, TRANSFORMING growth factors, PLATELET-derived growth factor, CONNECTIVE tissue growth factor, INDUCED pluripotent stem cells, TRANSFORMING growth factors-beta
Abstract

Introduction: Therapeutic interventions for intervertebral disc herniation remain scarce due to the inability of endogenous annulus fibrosus (AF) cells to respond to injury and drive tissue regeneration. Unlike other orthopedic tissues, such as cartilage, delivery of exogenous cells to the site of annular injury remains underdeveloped, largely due to a lack of an ideal cell source and the invasive nature of cell isolation. Human induced pluripotent stem cells (iPSCs) can be differentiated to specific cell fates using biochemical factors and are, therefore, an invaluable tool for cell therapy approaches. While differentiation protocols have been developed for cartilage and fibrous connective tissues (e.g., tendon), the signals that regulate the induction and differentiation of human iPSCs toward the AF fate remain unknown. Methods: iPSC‐derived sclerotome cells were treated with various combinations of developmental signals including transforming growth factor beta 3 (TGF‐β3), connective tissue growth factor (CTGF), platelet derived growth factor BB (PDGF‐BB), insulin‐like growth factor 1 (IGF‐1), or the Hedgehog pathway activator, Purmorphamine, and gene expression changes in major AF‐associated ECM genes were assessed. The top performing combination treatments were further validated by using three distinct iPSC lines and by assessing the production of upregulated ECM proteins of interest. To conduct a broader analysis of the transcriptomic shifts elicited by each factor combination, and to compare genetic profiles of treated cells to mature human AF cells, a 96.96 Fluidigm gene expression array was applied, and principal component analysis was employed to identify the transcriptional signatures of each cell population and treatment group in comparison to native AF cells. Results: TGF‐β3, in combination with PDGF‐BB, CTGF, or IGF‐1, induced an upregulation of key AF ECM genes in iPSC‐derived sclerotome cells. In particular, treatment with a combination of TGF‐β3 with PDGF‐BB for 14 days significantly increased gene expression of collagen II and aggrecan and increased protein deposition of collagen I and elastin compared to other treatment groups. Assessment of genes uniquely highly expressed by AF cells or SCL cells, respectively, revealed a shift toward the genetic profile of AF cells with the addition of TGF‐β3 and PDGF‐BB for 14 days. Discussion: These findings represent an initial approach to guide human induced pluripotent stem cells toward an AF‐like fate for cellular delivery strategies. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

36. Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects

Author

Galarraga, Jonathan H, Zlotnick, Hannah M, Locke, Ryan C, Gupta, Sachin, Fogarty, Natalie L, Masada, Kendall M, Stoeckl, Brendan D, Laforest, Lorielle, Castilho, Miguel, Malda, Jos, Levato, Riccardo, Carey, James L, Mauck, Robert L, Burdick, Jason A, Galarraga, Jonathan H, Zlotnick, Hannah M, Locke, Ryan C, Gupta, Sachin, Fogarty, Natalie L, Masada, Kendall M, Stoeckl, Brendan D, Laforest, Lorielle, Castilho, Miguel, Malda, Jos, Levato, Riccardo, Carey, James L, Mauck, Robert L, and Burdick, Jason A

Abstract

The surgical repair of articular cartilage remains an ongoing challenge in orthopedics. Tissue engineering is a promising approach to treat cartilage defects; however, scaffolds must (i) possess the requisite material properties to support neocartilage formation, (ii) exhibit sufficient mechanical integrity for handling during implantation, and (iii) be reliably fixed within cartilage defects during surgery. In this study, we demonstrate the reinforcement of soft norbornene-modified hyaluronic acid (NorHA) hydrogels via the melt electrowriting (MEW) of polycaprolactone to fabricate composite scaffolds that support encapsulated porcine mesenchymal stromal cell (pMSC, three donors) chondrogenesis and cartilage formation and exhibit mechanical properties suitable for handling during implantation. Thereafter, acellular MEW-NorHA composites or MEW-NorHA composites with encapsulated pMSCs and precultured for 28 days were implanted in full-thickness cartilage defects in porcine knees using either bioresorbable pins or fibrin glue to assess surgical fixation methods. Fixation of composites with either biodegradable pins or fibrin glue ensured implant retention in most cases (80%); however, defects treated with pinned composites exhibited more subchondral bone remodeling and inferior cartilage repair, as evidenced by micro-computed tomography (micro-CT) and safranin O/fast green staining, respectively, when compared to defects treated with glued composites. Interestingly, no differences in repair tissue were observed between acellular and cellularized implants. Additional work is required to assess the full potential of these scaffolds for cartilage repair. However, these results suggest that future approaches for cartilage repair with MEW-reinforced hydrogels should be carefully evaluated with regard to their fixation approach for construct retention and surrounding cartilage tissue damage.

Published
2023

37. Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects

Author

CS_Locomotion, Equine Musculoskeletal Biology, Locomotion - Equine Sciences, Galarraga, Jonathan H, Zlotnick, Hannah M, Locke, Ryan C, Gupta, Sachin, Fogarty, Natalie L, Masada, Kendall M, Stoeckl, Brendan D, Laforest, Lorielle, Castilho, Miguel, Malda, Jos, Levato, Riccardo, Carey, James L, Mauck, Robert L, Burdick, Jason A, CS_Locomotion, Equine Musculoskeletal Biology, Locomotion - Equine Sciences, Galarraga, Jonathan H, Zlotnick, Hannah M, Locke, Ryan C, Gupta, Sachin, Fogarty, Natalie L, Masada, Kendall M, Stoeckl, Brendan D, Laforest, Lorielle, Castilho, Miguel, Malda, Jos, Levato, Riccardo, Carey, James L, Mauck, Robert L, and Burdick, Jason A

Published
2023

38. Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects

Author

Galarraga, Jonathan H., Zlotnick, Hannah M., Locke, Ryan C., Gupta, Sachin, Fogarty, Natalie L., Masada, Kendall M., Stoeckl, Brendan D., Laforest, Lorielle, Castilho, Miguel, Malda, Jos, Levato, Riccardo, Carey, James L., Mauck, Robert L., Burdick, Jason A., Galarraga, Jonathan H., Zlotnick, Hannah M., Locke, Ryan C., Gupta, Sachin, Fogarty, Natalie L., Masada, Kendall M., Stoeckl, Brendan D., Laforest, Lorielle, Castilho, Miguel, Malda, Jos, Levato, Riccardo, Carey, James L., Mauck, Robert L., and Burdick, Jason A.

Abstract

The surgical repair of articular cartilage remains an ongoing challenge in orthopedics. Tissue engineering is a promising approach to treat cartilage defects; however, scaffolds must (i) possess the requisite material properties to support neocartilage formation, (ii) exhibit sufficient mechanical integrity for handling during implantation, and (iii) be reliably fixed within cartilage defects during surgery. In this study, we demonstrate the reinforcement of soft norbornene-modified hyaluronic acid (NorHA) hydrogels via the melt electrowriting (MEW) of polycaprolactone to fabricate composite scaffolds that support encapsulated porcine mesenchymal stromal cell (pMSC, three donors) chondrogenesis and cartilage formation and exhibit mechanical properties suitable for handling during implantation. Thereafter, acellular MEW-NorHA composites or MEW-NorHA composites with encapsulated pMSCs and precultured for 28 days were implanted in full-thickness cartilage defects in porcine knees using either bioresorbable pins or fibrin glue to assess surgical fixation methods. Fixation of composites with either biodegradable pins or fibrin glue ensured implant retention in most cases (80%); however, defects treated with pinned composites exhibited more subchondral bone remodeling and inferior cartilage repair, as evidenced by micro-computed tomography (micro-CT) and safranin O/fast green staining, respectively, when compared to defects treated with glued composites. Interestingly, no differences in repair tissue were observed between acellular and cellularized implants. Additional work is required to assess the full potential of these scaffolds for cartilage repair. However, these results suggest that future approaches for cartilage repair with MEW-reinforced hydrogels should be carefully evaluated with regard to their fixation approach for construct retention and surrounding cartilage tissue damage.

Published
2023

39. Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects

Author

Orthopaedie Onderzoek, Other research (not in main researchprogram), Regenerative Medicine and Stem Cells, Galarraga, Jonathan H., Zlotnick, Hannah M., Locke, Ryan C., Gupta, Sachin, Fogarty, Natalie L., Masada, Kendall M., Stoeckl, Brendan D., Laforest, Lorielle, Castilho, Miguel, Malda, Jos, Levato, Riccardo, Carey, James L., Mauck, Robert L., Burdick, Jason A., Orthopaedie Onderzoek, Other research (not in main researchprogram), Regenerative Medicine and Stem Cells, Galarraga, Jonathan H., Zlotnick, Hannah M., Locke, Ryan C., Gupta, Sachin, Fogarty, Natalie L., Masada, Kendall M., Stoeckl, Brendan D., Laforest, Lorielle, Castilho, Miguel, Malda, Jos, Levato, Riccardo, Carey, James L., Mauck, Robert L., and Burdick, Jason A.

Published
2023

40. Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz

Author

Jones, Dakota L., primary, Hallström, Grey F., additional, Jiang, Xi, additional, Locke, Ryan C., additional, Evans, Mary Kate, additional, Bonnevie, Edward D., additional, Srikumar, Anjana, additional, Leahy, Thomas P., additional, Nijsure, Madhura P., additional, Boerckel, Joel D., additional, Mauck, Robert L., additional, and Dyment, Nathaniel A., additional

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results