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3R inspired development and validation of osteochondral systems for joint repair and disease modelling Kyra Wing Yu Smith

Dissertations & Theses @ University of Pennsylvania Available online

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Format:
Book
Thesis/Dissertation
Author/Creator:
Smith, Kyra Wing Yu, author.
Contributor:
University of Pennsylvania. Bioengineering., degree granting institution.
Language:
English
Subjects (All):
Bioengineering.
Cellular biology.
Biomedical engineering.
Medicine.
0202.
0379.
0541.
0564.
Local Subjects:
Bioengineering.
Cellular biology.
Biomedical engineering.
Medicine.
0202.
0379.
0541.
0564.
Genre:
Academic theses
Physical Description:
1 online resource (230 pages)
Contained In:
Dissertations Abstracts International 87-12B
Place of Publication:
Ann Arbor : ProQuest Dissertations and Theses, 2026
Language Note:
English
Summary:
Musculoskeletal diseases are the leading cause of disability, and can affect any combination of tissues including bone, muscle, and connective tissue. Current research employs a myriad of in vitro and in vivo models to approach musculoskeletal disease research, but each model has its own benefits and shortcomings. Animal models can be difficult to finely control various factors and attempting to do so requires large sample sizes, therefore requiring great amounts of resources and funding. Similarly, not all animal models accurately represent human biology, and results may not be translationally relevant. To avoid this, many researchers are turning to in vitro models, but basic in vitro models have limited biological relevance, lacking both three-dimensional tissues as well as multiple tissue crosstalk. An in vitro model that easily recapitulates cross talk between different tissue types would allow researchers to more accurately develop in vitro disease models and control many factors prior to animal studies.In this work, I develop in vitro systems to model musculoskeletal tissues by supporting three-dimensional culture of multiple tissues and use this system to simulate disease and validate reparative strategies. I first use the bioreactor to probe success of an osteochondral scaffold prior to in vivo implantation, and to later prepare the osteochondral scaffold for in vivo validation. Next, I develop tissue constructs representative of the osteochondral junction and use the biphasic bioreactor to create an inflammatory environment mimetic of arthritis. This in vitro disease model allowed efficient studying cartilage-bone crosstalk in arthritis and located disease drivers as potential targets for therapeutics. The versatility of the proposed system, including compatibility with different materials and scales, will allow accommodation of numerous combinations of musculoskeletal tissues. These in vitro systems will help advance knowledge of disease development and treatment in musculoskeletal environments, as well as allow rapid testing of therapeutics and treatments
Notes:
Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
Advisors: Gottardi, Riccardo Committee members: Gullbrand, Sarah E.; Grayson, Warren L.; Mauck, Robert L.; Scanzello, Carla R.
Ph.D. University of Pennsylvania 2026
Vendor supplied data
Local Notes:
School code: 0175
ISBN:
9798247979494
Access Restriction:
Restricted for use by site license

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