Critical Review on the Physical and Mechanical Factors Involved in Tissue Engineering of Cartilage

Gaut, Carrie; Sugaya, Kimio

doi:10.2217/rme.15.31

Cited by 48 publications

(43 citation statements)

References 120 publications

(119 reference statements)

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“…For example, established clinical applications in cartilage repair make use of chondrocytes, which are encapsulated in fibrin within a polyglycol acid carrier fleece or are applied as spheroids, both posing only minimal initial mechanical stability. The load‐bearing features of the transplant develop in vivo promoted by environmental factors such as mechanical force, oxygen tension, and synovial fluid constituents . Mimicking those conditions during in vitro culture supports the generation of a mechanically robust cartilage models and is also mandatory for constructs composed of biodegradable materials to maintain stability, as the chondrocyte actively drive matrix turnover and tissue remodeling …”

Section: Discussionmentioning

confidence: 99%

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Lam¹,

et al. 2019

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To create artificial cartilage in vitro, mimicking the function of native extracellular matrix (ECM) and morphological cartilage‐like shape is essential. The interplay of cell patterning and matrix concentration has high impact on the phenotype and viability of the printed cells. To advance the capabilities of cartilage bioprinting, we investigated different ECMs to create an in vitro chondrocyte niche. Therefore, we used methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (HAMA) in a stereolithographic bioprinting approach. Both materials have been shown to support cartilage ECM formation and recovery of chondrocyte phenotype. We used these materials as bioinks to create cartilage models with varying chondrocyte densities. The models maintained shape, viability, and homogenous cell distribution over 14 days in culture. Chondrogenic differentiation was demonstrated by cartilage‐typical proteoglycan and type II collagen deposition and gene expression (COL2A1, ACAN) after 14 days of culture. The differentiation pattern was influenced by cell density. A high cell density print (25 × 106 cells/mL) led to enhanced cartilage‐typical zonal segmentation compared to cultures with lower cell density (5 × 106 cells/mL). Compared to HAMA, GelMA resulted in a higher expression of COL1A1, typical for a more premature chondrocyte phenotype. Both bioinks are feasible for printing in vitro cartilage with varying differentiation patterns and ECM organization depending on starting cell density and chosen bioink. The presented technique could find application in the creation of cartilage models and in the treatment of articular cartilage defects using autologous material and adjusting the bioprinted constructs size and shape to the patient. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2649–2657, 2019.

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Section: Discussionmentioning

confidence: 99%

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Lam¹,

et al. 2019

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“…Such signaling cues can be biochemical (e.g., growth factors, TGF‐β superfamily, fibroblast growth factor (FGF)‐2, or small molecules such as kartogenin), environmental (e.g., low oxygen concentrations compared to atmospheric air, hypoxia, to recapitulate the in vivo oxygen tensions of articular cartilage (1% O 2 in the deep zone to 6% O 2 in the superficial zone) as well as of most MSC niches (1–5% O 2 ) or physical factors (e.g., mechanical/electrical stimulation) . In fact, low oxygen tension culture conditions (generally between 3% and 5% O 2 ) have been employed to enhance MSC chondrogenesis in porous CTE scaffolds . Bioreactor technology has been successfully employed for the expansion of MSC and/or for chondrogenic priming, prior to tissue substitute fabrication.…”

Section: Introductionmentioning

confidence: 99%

Extruded Bioreactor Perfusion Culture Supports the Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells in 3D Porous Poly(ɛ‐Caprolactone) Scaffolds

Silva

Moura

Borrecho

et al. 2019

Biotechnology Journal

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Novel bioengineering strategies for the ex vivo fabrication of native-like tissue-engineered cartilage are crucial for the translation of these approaches to clinically manage highly prevalent and debilitating joint diseases. Bioreactors that provide different biophysical stimuli have been used in tissue engineering approaches aimed at enhancing the quality of the cartilage tissue generated. However, such systems are often highly complex, expensive, and not very versatile. In the current study, a novel, cost-effective, and customizable perfusion bioreactor totally fabricated by additive manufacturing (AM) is proposed for the study of the effect of fluid flow on the chondrogenic differentiation of human bone-marrow mesenchymal stem/stromal cells (hBMSCs) in 3D porous poly(ɛ-caprolactone) (PCL) scaffolds. hBMSCs are first seeded and grown on PCL scaffolds and hBMSC-PCL constructs are then transferred to 3D-extruded bioreactors for continuous perfusion culture under chondrogenic inductive conditions. Perfused constructs show similar cell metabolic activity and significantly higher sulfated glycosaminoglycan production (≈1.8-fold) in comparison to their non-perfused counterparts. Importantly, perfusion bioreactor culture significantly promoted the expression of chondrogenic marker genes while downregulating hypertrophy. This work highlights the potential of customizable AM platforms for the development of novel personalized repair strategies and more reliable in vitro models with a wide range of applications.

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“…The scaffolds prepared by the unidirectional freeze-thaw method have improved mechanical properties compared to those obtained by conventional freeze-thaw method. 45 Most importantly, no matter in the state of dry or swollen, the oriented scaffold could always possess anisotropic mechanical characteristics, which has been biomimetic the mechanical feature of cartilage in compression and will meet the demanding mechanical environment of the native tissue. As shown in Figure 3A, the weight losses of both scaffolds increased as the time goes on in PBS at 37 °C.…”

Section: Characterization Of Scaffoldsmentioning

confidence: 99%

A Biomimetic Poly(vinyl alcohol)–Carrageenan Composite Scaffold with Oriented Microarchitecture

Zhang¹,

Ye²,

Cui

et al. 2016

ACS Biomater. Sci. Eng.

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In general, the design of the scaffold should imitate certain advantageous properties of native extracellular matrix (ECM) in order to operate as a temporary ECM for cells. From this aspect, a biomimetic scaffold was prepared by using poly (vinyl alcohol) (PVA) and carrageenan (CAR), in which axially oriented pore structure can be formed through a facile unidirectional freeze-thaw method. We examined the feasibility of this oriented scaffold, which has better physico-chemical properties compared to non-oriented scaffold fabricated by conventional method. The microenvironment of this oriented scaffold could imitate biochemical and physical cues of natural cartilage ECM for guiding spatial organization and proliferation of cells in vitro, indicating its potential in cartilage repair strategy. Furthermore, the biocompatibility of the scaffold in vivo was demonstrated in a subcutaneous rat model, which revealed uniform infiltration and survival of newly formed tissue into oriented scaffold after 4 weeks, with only a minimal inflammatory response being observed over the course of the experiments. These results together indicated that the present biomimetic scaffold with oriented microarchitecture could be a promising candidate for cartilage tissue engineering.

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Critical Review on the Physical and Mechanical Factors Involved in Tissue Engineering of Cartilage

Cited by 48 publications

References 120 publications

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Extruded Bioreactor Perfusion Culture Supports the Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells in 3D Porous Poly(ɛ‐Caprolactone) Scaffolds

A Biomimetic Poly(vinyl alcohol)–Carrageenan Composite Scaffold with Oriented Microarchitecture

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