Translational Application of 3D Bioprinting for Cartilage Tissue Engineering

Cartilage is an avascular tissue with extremely limited self-regeneration capabilities. At present, there are no existing treatments that effectively stop the deterioration of cartilage or reverse its effects; current treatments merely relieve its symptoms and surgical intervention is required when the condition aggravates. Thus, cartilage damage remains an ongoing challenge in orthopaedics with an urgent need for improved treatment options. In recent years, major advances have been made in the development of three-dimensional (3D) bioprinted constructs for cartilage repair applications. 3D bioprinting is an evolutionary additive manufacturing technique that enables the precisely controlled deposition of a combination of biomaterials, cells, and bioactive molecules, collectively known as bioink, layer-by-layer to produce constructs that simulate the structure and function of native cartilage tissue. This review provides an insight into the current developments in 3D bioprinting for cartilage tissue engineering. The bioink and construct properties required for successful application in cartilage repair applications are highlighted. Furthermore, the potential for translation of 3D bioprinted constructs to the clinic is discussed. Overall, 3D bioprinting demonstrates great potential as a novel technique for the fabrication of tissue engineered constructs for cartilage regeneration, with distinct advantages over conventional techniques.

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3D Bioprinted Implants for Cartilage Repair in Intervertebral Discs and Knee Menisci

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.754113 ◽

2021 ◽

Vol 9 ◽

Author(s):

Kalindu Perera ◽

Ryan Ivone ◽

Evelina Natekin ◽

Cheryl. A. Wilga ◽

Jie Shen ◽

...

Keyword(s):

Tissue Engineering ◽

Cartilage Repair ◽

Donor Site ◽

Cartilage Tissue Engineering ◽

The United States ◽

Intervertebral Discs ◽

The Body ◽

Cartilage Tissue ◽

Cartilage Defects ◽

3D Bioprinting

Cartilage defects pose a significant clinical challenge as they can lead to joint pain, swelling and stiffness, which reduces mobility and function thereby significantly affecting the quality of life of patients. More than 250,000 cartilage repair surgeries are performed in the United States every year. The current gold standard is the treatment of focal cartilage defects and bone damage with nonflexible metal or plastic prosthetics. However, these prosthetics are often made from hard and stiff materials that limits mobility and flexibility, and results in leaching of metal particles into the body, degeneration of adjacent soft bone tissues and possible failure of the implant with time. As a result, the patients may require revision surgeries to replace the worn implants or adjacent vertebrae. More recently, autograft – and allograft-based repair strategies have been studied, however these too are limited by donor site morbidity and the limited availability of tissues for surgery. There has been increasing interest in the past two decades in the area of cartilage tissue engineering where methods like 3D bioprinting may be implemented to generate functional constructs using a combination of cells, growth factors (GF) and biocompatible materials. 3D bioprinting allows for the modulation of mechanical properties of the developed constructs to maintain the required flexibility following implantation while also providing the stiffness needed to support body weight. In this review, we will provide a comprehensive overview of current advances in 3D bioprinting for cartilage tissue engineering for knee menisci and intervertebral disc repair. We will also discuss promising medical-grade materials and techniques that can be used for printing, and the future outlook of this emerging field.

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Regeneration of Articular Cartilage Using Injectable Hybrid Polymer Hydrogel Incorporated With Nanoparticles

International Journal of Advanced Research in Science, Communication and Technology ◽

10.48175/ijarsct-1406 ◽

2021 ◽

pp. 394-397

Author(s):

T. Ruhina ◽

N. Mahdhia Begum ◽

S. Padmavathi ◽

I. Sahanajith ◽

K. Karthick Babu

Keyword(s):

Articular Cartilage ◽

Cartilage Repair ◽

Cartilage Damage ◽

Cartilage Tissue Engineering ◽

Treatment Strategies ◽

Bioactive Molecules ◽

Cartilage Tissue ◽

Human Beings ◽

Injectable Hydrogels ◽

Injectable Hydrogel

Cartilage damage is still a threat to human beings, yet there is currently no treatment available to fully restore the function of cartilage. Recently, due to their unique structures and properties, injectable hydrogels have been widely studied and have exhibited high potential for applications in therapeutic areas, especially in cartilage repair. In this review, briefly introduce the properties of cartilage, some articular cartilage injuries, and now available treatment strategies. Afterwards,the functional and fundamental requirements of injectable hydrogels in cartilage tissue engineering, as well as the main advantages of injectable hydrogels as a therapy for cartilage damage, including strong plasticity and excellent biocompatibility. Moreover, we comprehensively summarize the polymers, cells, and bioactive molecules regularly used in the fabrication of injectable hydrogel, with two kinds of gelation, i.e., physical and chemical crosslinking, which ensure the excellence design of injectable hydrogels for cartilage repair. We also include the novel hybrid injectable hydrogel incorporated with nanoparticles. Finally, we conclude with the advances of this clinical application and the challenges of injectable hydrogels used in cartilage.

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Advances and Prospects in Stem Cells for Cartilage Regeneration

Stem Cells International ◽

10.1155/2017/4130607 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 25

Author(s):

Mingjie Wang ◽

Zhiguo Yuan ◽

Ning Ma ◽

Chunxiang Hao ◽

Weimin Guo ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Regenerative Medicine ◽

Cartilage Repair ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Emerging Trends ◽

Systematic Understanding

The histological features of cartilage call attention to the fact that cartilage has a little capacity to repair itself owing to the lack of a blood supply, nerves, or lymphangion. Stem cells have emerged as a promising option in the field of cartilage tissue engineering and regenerative medicine and could lead to cartilage repair. Much research has examined cartilage regeneration utilizing stem cells. However, both the potential and the limitations of this procedure remain controversial. This review presents a summary of emerging trends with regard to using stem cells in cartilage tissue engineering and regenerative medicine. In particular, it focuses on the characterization of cartilage stem cells, the chondrogenic differentiation of stem cells, and the various strategies and approaches involving stem cells that have been used in cartilage repair and clinical studies. Based on the research into chondrocyte and stem cell technologies, this review discusses the damage and repair of cartilage and the clinical application of stem cells, with a view to increasing our systematic understanding of the application of stem cells in cartilage regeneration; additionally, several advanced strategies for cartilage repair are discussed.

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Digital Light Processing Bioprinted Human Chondrocyte-Laden Poly (γ-Glutamic Acid)/Hyaluronic Acid Bio-Ink towards Cartilage Tissue Engineering

Biomedicines ◽

10.3390/biomedicines9070714 ◽

2021 ◽

Vol 9 (7) ◽

pp. 714

Author(s):

Alvin Kai-Xing Lee ◽

Yen-Hong Lin ◽

Chun-Hao Tsai ◽

Wan-Ting Chang ◽

Tsung-Li Lin ◽

...

Keyword(s):

United States ◽

Tissue Engineering ◽

Hyaluronic Acid ◽

Glutamic Acid ◽

Cellular Proliferation ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

The United States ◽

Cartilage Injury ◽

Cartilage Tissue

Cartilage injury is the main cause of disability in the United States, and it has been projected that cartilage injury caused by osteoarthritis will affect 30% of the entire United States population by the year 2030. In this study, we modified hyaluronic acid (HA) with γ-poly(glutamic) acid (γ-PGA), both of which are common biomaterials used in cartilage engineering, in an attempt to evaluate them for their potential in promoting cartilage regeneration. As seen from the results, γ-PGA-GMA and HA, with glycidyl methacrylate (GMA) as the photo-crosslinker, could be successfully fabricated while retaining the structural characteristics of γ-PGA and HA. In addition, the storage moduli and loss moduli of the hydrogels were consistent throughout the curing durations. However, it was noted that the modification enhanced the mechanical properties, the swelling equilibrium rate, and cellular proliferation, and significantly improved secretion of cartilage regeneration-related proteins such as glycosaminoglycan (GAG) and type II collagen (Col II). The cartilage tissue proof with Alcian blue further demonstrated that the modification of γ-PGA with HA exhibited suitability for cartilage tissue regeneration and displayed potential for future cartilage tissue engineering applications. This study built on the previous works involving HA and further showed that there are unlimited ways to modify various biomaterials in order to further bring cartilage tissue engineering to the next level.

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TRENDS AND CHALLENGES OF CARTILAGE TISSUE ENGINEERING

Biomedical Engineering Applications Basis and Communications ◽

10.4015/s1016237209001209 ◽

2009 ◽

Vol 21 (03) ◽

pp. 149-155 ◽

Cited By ~ 2

Author(s):

Hsu-Wei Fang

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Growth Factors ◽

Bone Cells ◽

Cartilage Tissue Engineering ◽

Bioactive Molecules ◽

In Vivo Studies ◽

Cartilage Tissue

Cartilage injuries may be caused by trauma, biomechanical imbalance, or degenerative changes of joint. Unfortunately, cartilage has limited capability to spontaneous repair once damaged and may lead to progressive damage and degeneration. Cartilage tissue-engineering techniques have emerged as the potential clinical strategies. An ideal tissue-engineering approach to cartilage repair should offer good integration into both the host cartilage and the subchondral bone. Cells, scaffolds, and growth factors make up the tissue engineering triad. One of the major challenges for cartilage tissue engineering is cell source and cell numbers. Due to the limitations of proliferation for mature chondrocytes, current studies have alternated to use stem cells as a potential source. In the recent years, a lot of novel biomaterials has been continuously developed and investigated in various in vitro and in vivo studies for cartilage tissue engineering. Moreover, stimulatory factors such as bioactive molecules have been explored to induce or enhance cartilage formation. Growth factors and other additives could be added into culture media in vitro, transferred into cells, or incorporated into scaffolds for in vivo delivery to promote cellular differentiation and tissue regeneration.Based on the current development of cartilage tissue engineering, there exist challenges to overcome. How to manipulate the interactions between cells, scaffold, and signals to achieve the moderation of implanted composite differentiate into moderate stem cells to differentiate into hyaline cartilage to perform the optimum physiological and biomechanical functions without negative side effects remains the target to pursue.

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Advanced Hydrogels for Cartilage Tissue Engineering: Recent Progress and Future Directions

Polymers ◽

10.3390/polym13234199 ◽

2021 ◽

Vol 13 (23) ◽

pp. 4199

Author(s):

Mahshid Hafezi ◽

Saied Nouri Khorasani ◽

Mohadeseh Zare ◽

Rasoul Esmaeely Neisiany ◽

Pooya Davoodi

Keyword(s):

Tissue Engineering ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Biomechanical Properties ◽

Tissue Growth ◽

Cartilage Tissue ◽

Self Healing ◽

Advantages And Disadvantages ◽

Wide Range

Cartilage is a tension- and load-bearing tissue and has a limited capacity for intrinsic self-healing. While microfracture and arthroplasty are the conventional methods for cartilage repair, these methods are unable to completely heal the damaged tissue. The need to overcome the restrictions of these therapies for cartilage regeneration has expanded the field of cartilage tissue engineering (CTE), in which novel engineering and biological approaches are introduced to accelerate the development of new biomimetic cartilage to replace the injured tissue. Until now, a wide range of hydrogels and cell sources have been employed for CTE to either recapitulate microenvironmental cues during a new tissue growth or to compel the recovery of cartilaginous structures via manipulating biochemical and biomechanical properties of the original tissue. Towards modifying current cartilage treatments, advanced hydrogels have been designed and synthesized in recent years to improve network crosslinking and self-recovery of implanted scaffolds after damage in vivo. This review focused on the recent advances in CTE, especially self-healing hydrogels. The article firstly presents the cartilage tissue, its defects, and treatments. Subsequently, introduces CTE and summarizes the polymeric hydrogels and their advances. Furthermore, characterizations, the advantages, and disadvantages of advanced hydrogels such as multi-materials, IPNs, nanomaterials, and supramolecular are discussed. Afterward, the self-healing hydrogels in CTE, mechanisms, and the physical and chemical methods for the synthesis of such hydrogels for improving the reformation of CTE are introduced. The article then briefly describes the fabrication methods in CTE. Finally, this review presents a conclusion of prevalent challenges and future outlooks for self-healing hydrogels in CTE applications.

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Hydrogels for the Application of Articular Cartilage Tissue Engineering: A Review of Hydrogels

Advances in Materials Science and Engineering ◽

10.1155/2018/4368910 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Er-Yuan Chuang ◽

Chih-Wei Chiang ◽

Pei-Chun Wong ◽

Chih-Hwa Chen

Keyword(s):

Tissue Engineering ◽

Articular Cartilage ◽

Cartilage Damage ◽

Medical Science ◽

Cartilage Tissue Engineering ◽

Polymeric Materials ◽

Tissue Growth ◽

Cartilage Tissue ◽

Cellular Interaction ◽

Polymeric Hydrogels

The treatment of articular cartilage damage is a major task in the medical science of orthopedics. Hydrogels possess the ability to form multifunctional cartilage grafts since they possess polymeric swellability upon immersion in an aqueous phase. Polymeric hydrogels are capable of physiological swelling and greasing, and they possess the mechanical behavior required for use as articular cartilage substitutes. The chondrogenic phenotype of these materials may be enhanced by embedding living cells. Artificial hydrogels fabricated from biologically derived and synthesized polymeric materials are also used as tissue-engineering scaffolds; with their controlled degradation profiles, the release of stimulatory growth factors can be achieved. In order to make use of these hydrogels, cartilage implants were formulated in the laboratory to demonstrate the bionic mechanical behaviors of physiological cartilage. This paper discusses developments concerning the use of polymeric hydrogels for substituting injured cartilage tissue and assisting tissue growth. These gels are designed with consideration of their polymeric classification, mechanical strength, manner of biodegradation, limitations of the payload, cellular interaction, amount of cells in the 3D hydrogel, sustained release for the model drug, and the different approaches for incorporation into adjacent organs. This article also summarizes the different advantages, disadvantages, and the future prospects of hydrogels.

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