scholarly journals Harnessing Biomechanics to Develop Cartilage Regeneration Strategies

2015 ◽  
Vol 137 (2) ◽  
Author(s):  
Kyriacos A. Athanasiou ◽  
Donald J. Responte ◽  
Wendy E. Brown ◽  
Jerry C. Hu
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Biochemical Characterization ◽  
Articular Chondrocytes ◽  
Lysyl Oxidase ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Main Function ◽  
Mechanical Stimuli

As this review was prepared specifically for the American Society of Mechanical Engineers H.R. Lissner Medal, it primarily discusses work toward cartilage regeneration performed in Dr. Kyriacos A. Athanasiou's laboratory over the past 25 years. The prevalence and severity of degeneration of articular cartilage, a tissue whose main function is largely biomechanical, have motivated the development of cartilage tissue engineering approaches informed by biomechanics. This article provides a review of important steps toward regeneration of articular cartilage with suitable biomechanical properties. As a first step, biomechanical and biochemical characterization studies at the tissue level were used to provide design criteria for engineering neotissues. Extending this work to the single cell and subcellular levels has helped to develop biochemical and mechanical stimuli for tissue engineering studies. This strong mechanobiological foundation guided studies on regenerating hyaline articular cartilage, the knee meniscus, and temporomandibular joint (TMJ) fibrocartilage. Initial tissue engineering efforts centered on developing biodegradable scaffolds for cartilage regeneration. After many years of studying scaffold-based cartilage engineering, scaffoldless approaches were developed to address deficiencies of scaffold-based systems, resulting in the self-assembling process. This process was further improved by employing exogenous stimuli, such as hydrostatic pressure, growth factors, and matrix-modifying and catabolic agents, both singly and in synergistic combination to enhance neocartilage functional properties. Due to the high cell needs for tissue engineering and the limited supply of native articular chondrocytes, costochondral cells are emerging as a suitable cell source. Looking forward, additional cell sources are investigated to render these technologies more translatable. For example, dermis isolated adult stem (DIAS) cells show potential as a source of chondrogenic cells. The challenging problem of enhanced integration of engineered cartilage with native cartilage is approached with both familiar and novel methods, such as lysyl oxidase (LOX). These diverse tissue engineering strategies all aim to build upon thorough biomechanical characterizations to produce functional neotissue that ultimately will help combat the pressing problem of cartilage degeneration. As our prior research is reviewed, we look to establish new pathways to comprehensively and effectively address the complex problems of musculoskeletal cartilage regeneration.

scholarly journals The Application of Bioreactors for Cartilage Tissue Engineering: Advances, Limitations, and Future Perspectives

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Liwei Fu ◽  
Pinxue Li ◽  
Hao Li ◽  
Cangjian Gao ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Culture ◽  
Articular Cartilage ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Future Perspectives ◽  
Mechanical Environment ◽  
Biomechanical Stimuli ◽  
Articular Cartilage Regeneration

Tissue engineering (TE) has brought new hope for articular cartilage regeneration, as TE can provide structural and functional substitutes for native tissues. The basic elements of TE involve scaffolds, seeded cells, and biochemical and biomechanical stimuli. However, there are some limitations of TE; what most important is that static cell culture on scaffolds cannot simulate the physiological environment required for the development of natural cartilage. Recently, bioreactors have been used to simulate the physical and mechanical environment during the development of articular cartilage. This review aims to provide an overview of the concepts, categories, and applications of bioreactors for cartilage TE with emphasis on the design of various bioreactor systems.

scholarly journals Bioprinting of a Zonal-Specific Cell Density Scaffold: A Biomimetic Approach for Cartilage Tissue Engineering

2021 ◽  
Vol 11 (17) ◽  
pp. 7821
Author(s):  
Angeliki Dimaraki ◽  
Pedro J. Díaz-Payno ◽  
Michelle Minneboo ◽  
Mahdiyeh Nouri-Goushki ◽  
Maryam Hosseini ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Cell Density ◽  
Articular Chondrocytes ◽  
Cartilage Tissue Engineering ◽  
Smooth Transition ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Specific Cell ◽  
Cell Densities

The treatment of articular cartilage defects remains a significant clinical challenge. This is partially due to current tissue engineering strategies failing to recapitulate native organization. Articular cartilage is a graded tissue with three layers exhibiting different cell densities: the superficial zone having the highest density and the deep zone having the lowest density. However, the introduction of cell gradients for cartilage tissue engineering, which could promote a more biomimetic environment, has not been widely explored. Here, we aimed to bioprint a scaffold with different zonal cell densities to mimic the organization of articular cartilage. The scaffold was bioprinted using an alginate-based bioink containing human articular chondrocytes. The scaffold design included three cell densities, one per zone: 20 × 106 (superficial), 10 × 106 (middle), and 5 × 106 (deep) cells/mL. The scaffold was cultured in a chondrogenic medium for 25 days and analyzed by live/dead assay and histology. The live/dead analysis showed the ability to generate a zonal cell density with high viability. Histological analysis revealed a smooth transition between the zones in terms of cell distribution and a higher sulphated glycosaminoglycan deposition in the highest cell density zone. These findings pave the way toward bioprinting complex zonal cartilage scaffolds as single units, thereby advancing the translation of cartilage tissue engineering into clinical practice.

scholarly journals Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering

2020 ◽  
Vol 21 (3) ◽  
pp. 1004 ◽  
Author(s):  
Veronica Zubillaga ◽  
Ana Alonso-Varona ◽  
Susana C. M. Fernandes ◽  
Asier M. Salaberria ◽  
Teodoro Palomares
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Collagen Type ◽  
Porous Scaffold ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Type I ◽  
Low Oxygen ◽  
Porous Chitosan

Articular cartilage degeneration is one of the most common causes of pain and disability in middle-aged and older people. Tissue engineering (TE) has shown great therapeutic promise for this condition. The design of cartilage regeneration constructs must take into account the specific characteristics of the cartilaginous matrix, as well as the avascular nature of cartilage and its cells’ peculiar arrangement in isogenic groups. Keeping these factors in mind, we have designed a 3D porous scaffold based on genipin-crosslinked chitosan/chitin nanocrystals for spheroid chondral differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) induced in hypoxic conditions. First, we demonstrated that, under low oxygen conditions, the chondrospheroids obtained express cartilage-specific markers including collagen type II (COL2A1) and aggrecan, lacking expression of osteogenic differentiation marker collagen type I (COL1A2). These results were associated with an increased expression of hypoxia-inducible factor 1α, which positively directs COL2A1 and aggrecan expression. Finally, we determined the most suitable chondrogenic differentiation pattern when hASC spheroids were seeded in the 3D porous scaffold under hypoxia and obtained a chondral extracellular matrix with a high sulphated glycosaminoglycan content, which is characteristic of articular cartilage. These findings highlight the potential use of such templates in cartilage tissue engineering.

scholarly journals Articular cartilage tissue engineering with stem cells implanted onto nanoscaffolds and platelet-rich plasma

2017 ◽  
Vol 3 (3) ◽  
pp. 322
Author(s):  
Hadeer A. Abbassy ◽  
Laila M. Montaser ◽  
Sherin M. Fawzy
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Articular Cartilage ◽  
Soft Tissues ◽  
Platelet Rich Plasma ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Great Promise

<p class="abstract">Musculoskeletal medicine targets both cartilage regeneration and healing of soft tissues. Articular cartilage repair and regeneration is primarily considered to be due to its poor regenerative properties. Cartilage defects due to joint injury, aging, or osteoarthritis have low self-repair ability thus they are most often irreversible as well as being a major cause of joint pain and chronic disability. Unfortunately, current methods do not seamlessly restore hyaline cartilage and may lead to the formation of fibro- or continue hypertrophic cartilage. Deficiency of efficient modalities of therapy has invited research to combine stem cells, scaffold materials and environmental factors through tissue engineering. Articular cartilage tissue engineering aims to repair, regenerate, and hence improve the function of injured or diseased cartilage. This holds great potential and has evoked intense interest in improving cartilage therapy. Platelet-rich plasma (PRP) and/or stem cells may be influential for tissue repair as well as cartilage regenerative processes.  A great promise to advance current cartilage therapies toward achieving a consistently successful modality has been held for addressing cartilage afflictions. The use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology may be the best way to reach this objective via tissue engineering. A current and emergent approach in the field of cartilage tissue engineering is explained in this review for specific application. In the future, the development of new strategies using stem cells seeded in scaffolds and the culture medium supplemented with growth factors could improve the quality of the newly formed cartilage<span lang="EN-IN">.</span></p>

scholarly journals Applications of Biocompatible Scaffold Materials in Stem Cell-Based Cartilage Tissue Engineering

2021 ◽  
Vol 9 ◽  
Author(s):  
Xia Zhao ◽  
Daniel A. Hu ◽  
Di Wu ◽  
Fang He ◽  
Hao Wang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Articular Chondrocytes ◽  
Critical Role ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
3D Bioprinting ◽  
Repair Capacity ◽  
Scaffold Materials

Cartilage, especially articular cartilage, is a unique connective tissue consisting of chondrocytes and cartilage matrix that covers the surface of joints. It plays a critical role in maintaining joint durability and mobility by providing nearly frictionless articulation for mechanical load transmission between joints. Damage to the articular cartilage frequently results from sport-related injuries, systemic diseases, degeneration, trauma, or tumors. Failure to treat impaired cartilage may lead to osteoarthritis, affecting more than 25% of the adult population globally. Articular cartilage has a very low intrinsic self-repair capacity due to the limited proliferative ability of adult chondrocytes, lack of vascularization and innervation, slow matrix turnover, and low supply of progenitor cells. Furthermore, articular chondrocytes are encapsulated in low-nutrient, low-oxygen environment. While cartilage restoration techniques such as osteochondral transplantation, autologous chondrocyte implantation (ACI), and microfracture have been used to repair certain cartilage defects, the clinical outcomes are often mixed and undesirable. Cartilage tissue engineering (CTE) may hold promise to facilitate cartilage repair. Ideally, the prerequisites for successful CTE should include the use of effective chondrogenic factors, an ample supply of chondrogenic progenitors, and the employment of cell-friendly, biocompatible scaffold materials. Significant progress has been made on the above three fronts in past decade, which has been further facilitated by the advent of 3D bio-printing. In this review, we briefly discuss potential sources of chondrogenic progenitors. We then primarily focus on currently available chondrocyte-friendly scaffold materials, along with 3D bioprinting techniques, for their potential roles in effective CTE. It is hoped that this review will serve as a primer to bring cartilage biologists, synthetic chemists, biomechanical engineers, and 3D-bioprinting technologists together to expedite CTE process for eventual clinical applications.

scholarly journals Relevant Local Fatwā on The Issues of Using Human Tissues in Articular Cartilage Tissue Engineering Experimentation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Muhammad Aa’zamuddin AR ◽  
Nur Syamimi MA ◽  
Abdurezak AH ◽  
Azhim A ◽  
Munirah S
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Biological Samples ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Joint Disease ◽  
Cartilage Tissue ◽  
Medical Procedure ◽  
Human Donor ◽  
Articular Cartilage Regeneration

In articular cartilage tissue engineering (ACTE) experimentation, the researchers have utilised cells and tissues sampled from the human donor for research purposes. The cells and tissues may be harvested from the living donor’s discarded tissues through a medical procedure, e.g. the total knee replacement surgery. The small pieces of a tissue sample taken from the human donor are essential to study the articular cartilage regeneration for treating joint disease, i.e. osteoarthritis. However, the procedure has raised some ethical and fiqh (Islamic jurisprudence) concerns. The study was done by utilising the secondary analysis of local Muslim jurists’ opinions (fatwā) related to the sampling of human biological samples. This paper explores the scenarios of using cell sources taken from the living human donor through the existing fatwā of local Muslim jurists (fuqahā`). The scenarios include: (1) taking samples from the living donor, and (2) discarding human tissue, as practised in ACTE experimentation. The current fatwā has shown that honouring every part of a human body is considered essential in Islam. ACTE researchers may utilise the biological samples from living donors as alternatives in studying articular cartilage regeneration. The donation of human biological samples for research purposes in ACTE experimentation, obtained from a medical procedure, may be permissible, should the stipulated terms and conditions were observed, and the procedure does not cause any additional harm to the donor.

The role of mechanical regulation in cartilage tissue engineering

2021 ◽  
Vol 16 ◽  
Author(s):  
Shujiang Zhang ◽  
Yongchang Yao
Keyword(s):  
Tissue Engineering ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Mechanical Stimuli ◽  
And Function ◽  
Engineered Cartilage ◽  
Potential Use

: Due to the lack of vascular distribution and the slow metabolism, cartilage tissue cannot repair itself, which remains a huge challenge for cartilage regeneration. Tissue engineering using stem cells appears to be a promising method for cartilage repair. Tissue engineers demonstrated that mechanical stimulation can enhance the quality of engineered cartilage, making it more similar to natural cartilage in structure and function. In this review, we summarize recent studies on the role of mechanical stimuli in chondrogenesis, focusing on the applications of extrinsic mechanical loading and the studies on mechanical properties of biomaterials in cartilage tissue engineering. This review will provide fresh insights into the potential use of mechanical stimuli for clinical use.

scholarly journals Identifying the Potential of Qur’anic Recitation on the Proliferation of Chondrocytes Derived from Rabbit Articular Cartilage: Work in Progress

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Rosyafirah Hashim ◽  
Munirah Sha’ban ◽  
Sarah Rahmat ◽  
Zainul Ibrahim Zainuddin
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Profile Analysis ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
The Times ◽  
And Control ◽  
Rabbit Articular Cartilage

Introduction: In Islamic practice, the use of Qur’anic recitation in treatment can be traced back to the times of Prophet Muhammad (PBUH). This preliminary study aims to identify the potential of Qur’anic recitation of Surah Al-Fatihah on the proliferation of chondrocytes derived from rabbit articular cartilage. Cartilage tissue engineering offers an alternative way to facilitate cartilage regeneration in-vitro. Materials and Methods: The cellular model was established using a serially cultured and expanded chondrocytes in-vitro. The model was assigned into three groups. The first group was exposed to the Surah Al-Fatihah, recited 17 times based on the five times daily prayer unit (Raka’ah) obligated upon Muslims. The second group was exposed to an Arabic poem recitation. The third group was not exposed to any sound and served as the control. All groups were subjected to the growth profile analysis. The analysis was conducted at different passages starting from passage 0 to passage 3. Results: The results showed that the cells proliferation based on the growth kinetic analysis is higher for the cells exposed with Qur’anic recitation as compared to the Arabic poem and control groups. Conclusions: The proliferation process of the rabbit articular cartilage might be influenced with the use of Qur’anic recitation and as well as Arabic poem recitation. Exposure to the Western poem recitation and mute sound will be added for future study. It is hoped that this study could shed some light on the potential use of the Qur’anic recitation to facilitate cartilage regeneration in tissue engineering studies.

scholarly journals Approximate Optimization Study of Light Curing Waterborne Polyurethane Materials for the Construction of 3D Printed Cytocompatible Cartilage Scaffolds

Materials ◽  
2021 ◽  
Vol 14 (22) ◽  
pp. 6804
Author(s):  
Yi-Wen Chen ◽  
Ming-You Shie ◽  
Wen-Ching Chang ◽  
Yu-Fang Shen
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Joint Replacement ◽  
Cell Attachment ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Friction Reduction ◽  
Cartilage Tissue ◽  
Light Curing

Articular cartilage, which is a white transparent tissue with 1–2 mm thickness, is located in the interface between the two hard bones. The main functions of articular cartilage are stress transmission, absorption, and friction reduction. The cartilage cannot be repaired and regenerated once it has been damaged, and it needs to be replaced by artificial joints. Many approaches, such as artificial joint replacement, hyaluronic acid injection, microfracture surgery and cartilage tissue engineering have been applied in clinical treatment. Basically, some of these approaches are foreign material implantation for joint replacement to reach the goal of pain reduction and mechanism support. This study demonstrated another frontier in the research of cartilage reconstruction by applying regeneration medicine additive manufacturing (3D Printing) and stem cell technology. Light curing materials have been modified and tested to be printable and cytocompatible for stem cells in this research. Design of experiments (DOE) is adapted in this investigation to search for the optimal manufacturing parameter for biocompatible scaffold fabrication and stem cell attachment and growth. Based on the results, an optimal working process of biocompatible and printable scaffolds for cartilage regeneration is reported. We expect this study will facilitate the development of cartilage tissue engineering.

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