Millions of American suffer from Osteoarthritis (OA) while available medicines only alleviate symptoms but do not actually treat this disease. Surgically, the golden method so far has been to use substitutive tissue grafts which can be obtained from the same patients (i.e. auto-grafts) or other donors (e.g. allo-grafts) or constructed by tissue-engineering approach. However, these replacement grafts often suffer from mechanical failures and long-term instability. Many of them fail to regenerate hyaline cartilages which are required for healthy load- bearing cartilage tissues. Joint-loading, directly applied on cartilage tissues during joint-motions, plays a significant role for such mechanical failures and regenerative capability of replacement cartilage grafts. While joint-force, beyond a certain range, damages the cartilages, the force with appropriate magnitudes can promote healing of injured tissues. Despite numerous evidences on the important role of joint-loading, studies and applications of mechanical stimulation for the treatment of OA are very limited in in vivo conditions and clinical settings. This limitation mainly stems from the lack of information about actual joint-force which is directly applied on replacement cartilage grafts during motion of joints in vivo. To obtain such information, it is thus needed to develop a special force sensor that can possess several desired functions and properties. First, the tools need to be ultrathin and can be seamlessly integrated with replacement cartilage grafts to avoid being detached and disturbing the joint?s complex mechanics during implantation. Second, the sensors should be bioresorbable to not interfere in tissue regeneration and avoid any invasive removal surgery, which would damage the directly- interfaced cartilages. And finally, the sensor can provide a continuous real-time monitoring of the force during joint motions in vivo. Here, we will study, for the first time, a device-cartilage interface between the piezoelectric PLLA pressure sensor and a replacement cartilage auto-graft, which together can monitor in vivo joint-loading and heal cartilage-defects. The sensor system will provide accurate and reliable information about joint-loading, which can be used to track OA-evolution/cause in relation with cartilage-force and ultimately, combined with physical therapy or other mechanical stimulations to induce an optimal joint-force for the best cartilage regeneration in vivo. The sensor will be then self-degraded, facilitating tissue ingrowth and avoiding any invasive removal surgery. Accordingly, our proposal has two specific aims.
Aim 1 is to assess functional lifetime, degradation profile and performance of the proposed biodegradable PLLA sensors for measuring simulated joint-loading in vitro.
Aim 2 is to assess the healing of cartilage defects, receiving autografts integrated with the PLLA sensors and demonstrate reliability of the sensors to wirelessly measure real-time joint- loading in vivo.

Public Health Relevance

In this proposal, we aim to develop and study an innovative sensor/cartilage interface which can repair cartilage defects and wirelessly monitor in vivo joint-loading. The interface will be extremely valuable to studying the cause of osteoarthritis (OA) in different patient populations and facilitating the use of mechanical stimulation (e.g. through physical exercise, distraction methods, off-loading knee braces etc.) for promoting cartilage-healing in OA patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR078744-01
Application #
10167108
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Zheng, Xincheng
Project Start
2021-03-01
Project End
2023-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
1
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
614209054
City
Storrs-Mansfield
State
CT
Country
United States
Zip Code
06269