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Bioengineering
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Precision Medicine and Emerging Technologies for Osteoarthritis
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Precision Medicine and Emerging Technologies for Osteoarthritis

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Biomedical Engineering and Biomaterials".

Deadline for manuscript submissions: closed (25 December 2023) | Viewed by 7021

Special Issue Editor

Dr. Chathuraka T. Jayasuriya

E-Mail Website
Guest Editor
Department of Orthopaedics, Warren Alpert Medical School of Brown University and the Rhode Island Hospital, Providence, RI 02903, USA
Interests: regenerative medicine; tissue engineering; molecular & cell biology; stem & progenitor cells

Special Issue Information

Dear Colleagues,

Osteoarthritis (OA) is a complex disease with no concurrent cure. However, technologies are actively being developed to improve our understanding of OA and its risk factors to help us to more effectively treat and/or prevent its development. This Special Issue of Bioengineering highlights some of these advances in technology and medicine. Covered areas of interest include (but are not limited to) technologies designed to:

  • Better understand OA disease pathology;
  • Detect early stages of its development;
  • Prevent cartilage hypertrophy;
  • Prevent cartilage catabolism;
  • Effectively deliver drugs/precision medicine into cartilage;
  • Joint tissue crosstalk.

Dr. Chathuraka T. Jayasuriya
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Bioengineering is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • osteoarthritis
  • cartilage
  • chondrocyte
  • drug delivery
  • chondrogenesis

Published Papers (5 papers)

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Research

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16 pages, 6650 KiB  
Article
Improved Cartilage Protection with Low Molecular Weight Hyaluronic Acid Hydrogel
by Riley B. Brackin, Gail E. McColgan, Saitheja A. Pucha, Michael A. Kowalski, Hicham Drissi, Thanh N. Doan and Jay M. Patel
Bioengineering 2023, 10(9), 1013; https://doi.org/10.3390/bioengineering10091013 - 27 Aug 2023
Viewed by 1417
Abstract
Traumatic joint injuries are common, leading to progressive tissue degeneration and the development of osteoarthritis. The post-traumatic joint experiences a pro-inflammatory milieu, initiating a subtle but deteriorative process in cartilage tissue. To prevent or even reverse this process, our group previously developed a [...] Read more.
Traumatic joint injuries are common, leading to progressive tissue degeneration and the development of osteoarthritis. The post-traumatic joint experiences a pro-inflammatory milieu, initiating a subtle but deteriorative process in cartilage tissue. To prevent or even reverse this process, our group previously developed a tissue-penetrating methacrylated hyaluronic acid (MeHA) hydrogel system, crosslinked within cartilage to restore and/or protect the tissue. In the current study, we further optimized this approach by investigating the impact of biomaterial molecular weight (MW; 20, 75, 100 kDa) on its integration within and reinforcement of cartilage, as well as its ability to protect tissue degradation in a catabolic state. Indeed, the low MW MeHA integrated and reinforced cartilage tissue better than the high MW counterparts. Furthermore, in a 2 week IL-1β explant culture model, the 20 kDa MeHA demonstrated the most protection from biphasic mechanical loss, best retention of proteoglycans (Safranin O staining), and least aggrecan breakdown (NITEGE). Thus, the lower MW MeHA gels integrated better into the tissue and provided the greatest protection of the cartilage matrix. Future work will test this formulation in a preclinical model, with the goal of translating this therapeutic approach for cartilage preservation. Full article
(This article belongs to the Special Issue Precision Medicine and Emerging Technologies for Osteoarthritis)
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17 pages, 5953 KiB  
Article
Early Degenerative Changes in a Spontaneous Osteoarthritis Model Assessed by Nanoindentation
by Sarah Davis, Jurgita Zekonyte, Aikaterina Karali, Marta Roldo and Gordon Blunn
Bioengineering 2023, 10(9), 995; https://doi.org/10.3390/bioengineering10090995 - 23 Aug 2023
Cited by 1 | Viewed by 851
Abstract
Understanding early mechanical changes in articular cartilage (AC) and subchondral bone (SB) is crucial for improved treatment of osteoarthritis (OA). The aim of this study was to develop a method for nanoindentation of fresh, unfixed osteochondral tissue to assess the early changes in [...] Read more.
Understanding early mechanical changes in articular cartilage (AC) and subchondral bone (SB) is crucial for improved treatment of osteoarthritis (OA). The aim of this study was to develop a method for nanoindentation of fresh, unfixed osteochondral tissue to assess the early changes in the mechanical properties of AC and SB. Nanoindentation was performed throughout the depth of AC and SB in the proximal tibia of Dunkin Hartley guinea pigs at 2 months, 3 months, and 2 years of age. The contralateral tibias were either histologically graded for OA or analyzed using immunohistochemistry. The results showed an increase in the reduced modulus (Er) in the deep zone of AC during early-stage OA (6.0 ± 1.75 MPa) compared to values at 2 months (4.04 ± 1.25 MPa) (*** p < 0.001). In severe OA (2-year) specimens, there was a significant reduction in Er throughout the superficial and middle AC zones, which correlated to increased ADAMTS 4 and 5 staining, and proteoglycan loss in these regions. In the subchondral bone, a 35.0% reduction in stiffness was observed between 2-month and 3-month specimens (*** p < 0.001). The severe OA age group had significantly increased SB stiffness of 36.2% and 109.6% compared to 2-month and 3-month-old specimens respectively (*** p < 0.001). In conclusion, this study provides useful information about the changes in the mechanical properties of both AC and SB during both early- and late-stage OA and indicates that an initial reduction in stiffness of the SB and an increase in stiffness in the deep zone of AC may precede early-stage cartilage degeneration. Full article
(This article belongs to the Special Issue Precision Medicine and Emerging Technologies for Osteoarthritis)
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14 pages, 1361 KiB  
Article
Long-Term Bilateral Neuromuscular Function and Knee Osteoarthritis after Anterior Cruciate Ligament Reconstruction
by Payam Zandiyeh, Lauren R. Parola, Meggin Q. Costa, Madalyn J. Hague, Janine Molino, Braden C. Fleming and Jillian E. Beveridge
Bioengineering 2023, 10(7), 812; https://doi.org/10.3390/bioengineering10070812 - 06 Jul 2023
Cited by 1 | Viewed by 1303
Abstract
Neuromuscular function is thought to contribute to posttraumatic osteoarthritis (PTOA) risk in anterior cruciate ligament (ACL)-reconstructed (ACLR) patients, but sensitive and easy-to-use tools are needed to discern whether complex muscle activation strategies are beneficial or maladaptive. Using an electromyography (EMG) signal analysis technique [...] Read more.
Neuromuscular function is thought to contribute to posttraumatic osteoarthritis (PTOA) risk in anterior cruciate ligament (ACL)-reconstructed (ACLR) patients, but sensitive and easy-to-use tools are needed to discern whether complex muscle activation strategies are beneficial or maladaptive. Using an electromyography (EMG) signal analysis technique coupled with a machine learning approach, we sought to: (1) identify whether ACLR muscle activity patterns differed from those of healthy controls, and (2) explore which combination of patient outcome measures (thigh muscle girth, knee laxity, hop distance, and activity level) predicted the extent of osteoarthritic changes via magnetic resonance imaging (MRI) in ACLR patients. Eleven ACLR patients 10–15 years post-surgery and 12 healthy controls performed a hop activity while lower limb muscle EMG was recorded bilaterally. Osteoarthritis was evaluated based on MRI. ACLR muscle activity patterns were bilaterally symmetrical and differed from those of healthy controls, suggesting the presence of a global adaptation strategy. Smaller ipsilateral thigh muscle girth was the strongest predictor of inferior MRI scores. The ability of our EMG analysis approach to detect meaningful neuromuscular differences that could ultimately be related to thigh muscle girth provides the foundation to further investigate a direct link between muscle activation patterns and PTOA risk. Full article
(This article belongs to the Special Issue Precision Medicine and Emerging Technologies for Osteoarthritis)
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20 pages, 7040 KiB  
Article
Responding to ACL Injury and its Treatments: Comparative Gene Expression between Articular Cartilage and Synovium
by Jonah I. Donnenfield, Benedikt L. Proffen, Braden C. Fleming and Martha M. Murray
Bioengineering 2023, 10(5), 527; https://doi.org/10.3390/bioengineering10050527 - 26 Apr 2023
Viewed by 1286
Abstract
The relationship between cartilage and synovium is a rapidly growing area of osteoarthritis research. However, to the best of our knowledge, the relationships in gene expression between these two tissues have not been explored in mid-stage disease development. The current study compared the [...] Read more.
The relationship between cartilage and synovium is a rapidly growing area of osteoarthritis research. However, to the best of our knowledge, the relationships in gene expression between these two tissues have not been explored in mid-stage disease development. The current study compared the transcriptomes of these two tissues in a large animal model one year following posttraumatic osteoarthritis induction and multiple surgical treatment modalities. Thirty-six Yucatan minipigs underwent transection of the anterior cruciate ligament. Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair augmented with an extracellular matrix (ECM) scaffold, followed by RNA sequencing of the articular cartilage and synovium at 52 weeks after harvest. Twelve intact contralateral knees served as controls. Across all treatment modalities, the primary difference in the transcriptomes was that the articular cartilage had greater upregulation of genes related to immune activation compared to the synovium—once baseline differences between cartilage and synovium were adjusted for. Oppositely, synovium featured greater upregulation of genes related to Wnt signaling compared to articular cartilage. After adjusting for expression differences between cartilage and synovium seen following ligament reconstruction, ligament repair with an ECM scaffold upregulated pathways related to ion homeostasis, tissue remodeling, and collagen catabolism in cartilage relative to synovium. These findings implicate inflammatory pathways within cartilage in the mid-stage development of posttraumatic osteoarthritis, independent of surgical treatment. Moreover, use of an ECM scaffold may exert a chondroprotective effect over gold-standard reconstruction through preferentially activating ion homeostatic and tissue remodeling pathways within cartilage. Full article
(This article belongs to the Special Issue Precision Medicine and Emerging Technologies for Osteoarthritis)
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Review

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17 pages, 1322 KiB  
Review
Suppressing Chondrocyte Hypertrophy to Build Better Cartilage
by Christian Shigley, Jay Trivedi, Ozair Meghani, Brett D. Owens and Chathuraka T. Jayasuriya
Bioengineering 2023, 10(6), 741; https://doi.org/10.3390/bioengineering10060741 - 20 Jun 2023
Cited by 1 | Viewed by 1558
Abstract
Current clinical strategies for restoring cartilage defects do not adequately consider taking the necessary steps to prevent the formation of hypertrophic tissue at injury sites. Chondrocyte hypertrophy inevitably causes both macroscopic and microscopic level changes in cartilage, resulting in adverse long-term outcomes following [...] Read more.
Current clinical strategies for restoring cartilage defects do not adequately consider taking the necessary steps to prevent the formation of hypertrophic tissue at injury sites. Chondrocyte hypertrophy inevitably causes both macroscopic and microscopic level changes in cartilage, resulting in adverse long-term outcomes following attempted restoration. Repairing/restoring articular cartilage while minimizing the risk of hypertrophic neo tissue formation represents an unmet clinical challenge. Previous investigations have extensively identified and characterized the biological mechanisms that regulate cartilage hypertrophy with preclinical studies now beginning to leverage this knowledge to help build better cartilage. In this comprehensive article, we will provide a summary of these biological mechanisms and systematically review the most cutting-edge strategies for circumventing this pathological hallmark of osteoarthritis. Full article
(This article belongs to the Special Issue Precision Medicine and Emerging Technologies for Osteoarthritis)
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