Integrating melt electrowriting and inkjet bioprinting for engineering structurally organized articular cartilage

Dufour, Alexandre; Gallostra, X. Barceló; O’Keeffe, Clodagh; Eichholz, Kian F.; Euw, Stanislas Von; Garcia, Orquidea; Kelly, Daniel J.

doi:10.1016/j.biomaterials.2022.121405

Cited by 51 publications

(36 citation statements)

References 70 publications

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“…Cells were then bioprinted into each chamber to grow into spheroids. After in vitro culture, spheroids integrate into the polymer, forming a unique hybrid graft [ 42 ].…”

Section: Bioassembly Methodsmentioning

confidence: 99%

“…A mixture of cells and hydrogel were loaded to the ‘cleaned and sterilized’ ink cartridge and deposited dropwise [ 41 ]. For better control and performance, various custom-made inkjet bioprinters have been reported, with most using thermal ( Figure 1 F) or piezoelectric ( Figure 1 G) actuator-driven droplet techniques [ 42 ]. The volume of droplets generated by a thermal actuator can be altered by varying the temperature gradient or by increasing the frequency of the pressure pulses.…”

Section: Spherical Building Blocks Manufacturementioning

confidence: 99%

“…Void spaces, immature cartilage tissue, and cell death were observed ( E4 , histology). (Figures adapted from [ 17 , 42 , 77 , 80 , 92 , 93 ]).…”

Section: Figurementioning

confidence: 99%

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Articular Cartilage Regeneration through Bioassembling Spherical Micro-Cartilage Building Blocks

Grottkau¹,

Hui²,

Pang³

2022

Cells

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Articular cartilage lesions are prevalent and affect one out of seven American adults and many young patients. Cartilage is not capable of regeneration on its own. Existing therapeutic approaches for articular cartilage lesions have limitations. Cartilage tissue engineering is a promising approach for regenerating articular neocartilage. Bioassembly is an emerging technology that uses microtissues or micro-precursor tissues as building blocks to construct a macro-tissue. We summarize and highlight the application of bioassembly technology in regenerating articular cartilage. We discuss the advantages of bioassembly and present two types of building blocks: multiple cellular scaffold-free spheroids and cell-laden polymer or hydrogel microspheres. We present techniques for generating building blocks and bioassembly methods, including bioprinting and non-bioprinting techniques. Using a data set of 5069 articles from the last 28 years of literature, we analyzed seven categories of related research, and the year trends are presented. The limitations and future directions of this technology are also discussed.

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“…Cells were then bioprinted into each chamber to grow into spheroids. After in vitro culture, spheroids integrate into the polymer, forming a unique hybrid graft [ 42 ].…”

Section: Bioassembly Methodsmentioning

confidence: 99%

Section: Spherical Building Blocks Manufacturementioning

confidence: 99%

See 1 more Smart Citation

Articular Cartilage Regeneration through Bioassembling Spherical Micro-Cartilage Building Blocks

Grottkau¹,

Hui²,

Pang³

2022

Cells

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“…In 2021, Meng et al used MEW to produce high precision PLLA scaffolds and studied the in vitro potential for bone tissue engineering [ 33 ]. Recently, Dufour et al published their approach of combining bioprinting and MEW to engineer structurally organized articular cartilage constructs [ 34 ]. In another study, the effect of MEW fibre orientation on cellular organization in the context of anterior cruciate ligament engineering was studied [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanical and Biological Evaluation of Melt-Electrowritten Polycaprolactone Scaffolds for Acetabular Labrum Restoration

Santschi

Huber

Bujalka

et al. 2022

Cells

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Repair or reconstruction of a degenerated or injured acetabular labrum is essential to the stability and health of the hip joint. Current methods for restoration fail to reproduce the structure and mechanical properties of the labrum. In this study, we characterized the structure and tensile mechanical properties of melt-electrowritten polycaprolactone scaffolds of varying architectures and assessed the labrum cell compatibility of selected graft candidates. Cell compatibility was assessed using immunofluorescence of the actin skeleton. First, labrum explants were co-cultured with scaffold specimen to investigate the scaffold compatibility with primary cells. Second, effects of pore size on pre-cultured seeded labrum cells were studied. Third, cell compatibility under dynamic stretching was examined. Grid-like structures showed favorable tensile properties with decreasing fibre spacing. Young’s moduli ranging from 2.33 ± 0.34 to 13.36 ± 2.59 MPa were measured across all structures. Primary labrum cells were able to migrate from co-cultured labrum tissue specimens into the scaffold and grow in vitro. Incorporation of small-diameter-fibre and interfibre spacing improved cell distribution and cell spreading, whereas mechanical properties were only marginally affected. Wave-patterned constructs reproduced the non-linear elastic behaviour of native labrum tissue and, therefore, allowed for physiological cyclic tensile strain but showed decreased cell compatibility under dynamic loading. In conclusion, melt-electrowritten polycaprolactone scaffolds are promising candidates for labral grafts; however, further development is required to improve both the mechanical and biological compatibility.

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“…In the context of cartilage tissue engineering, recapitulation of the physiological stratification found in native articular cartilage (AC) is rarely reported. Although the use of instructive scaffolds that provide boundary conditions to the developing tissue have gone some of the way in addressing the challenge of generating a stratified AC [9,[38][39][40], complete recapitulation of the zonal organisation within engineered cartilage tissues remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Temporal enzymatic treatment to enhance the remodelling of multiple cartilage microtissues into a structurally organised tissue

Burdis

Gallostra

Kelly

2022

Preprint

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Scaffold-free tissue engineering strategies aim to recapitulate key aspects of normal developmental processes as a means of generating highly biomimetic grafts. Cartilage and fibrocartilaginous tissues have successfully been engineered by bringing together large numbers of cells, cellular aggregates or microtissues and allowing them to self-assemble or self-organize into a functional graft. Despite the promise of such approaches, considerable challenges still remain, such as engineering scaled-up tissues with predefined geometries, ensuring robust fusion between adjacent cellular aggregates or microtissues, and directing the (re)modelling of such biological building blocks into a unified scaled-up graft with hierarchical matrix organisation mimetic of the native tissue. In this study, we first demonstrate the benefits of engineering cartilage via the fusion of multiple cartilage microtissues compared to conventional scaffold-free approaches where (millions of) individual cells are allowed to aggregate and generate a cartilaginous graft. Key advantages include the engineering of a tissue with a richer extracellular matrix, a more hyaline-like cartilage phenotype and a final graft which better matched the intended geometry. A major drawback associated with this approach is that individual microtissues did not completely (re)model and remnants of their initial architectures where still evident throughout the macrotissue. In an attempt to address this limitation, the enzyme chondroitinase ABC (cABC) was employed to accelerate structural (re)modelling of the engineered tissue. Temporal enzymatic treatment supported robust fusion between adjacent microtissues, enhanced microtissue (re)modelling and supported the development of a more biomimetic tissue with a zonally organised collagen architecture. Additionally, we observed that cABC treatment modulated matrix composition (rebalancing the collagen:glycosaminoglycans ratio), tissue phenotype, and to a lesser extent, tissue mechanics. Ultimately, this work demonstrates that microtissue self-organisation is an effective method for engineering scaled-up cartilage grafts with a pre-defined geometry and near-native levels of ECM accumulation. Importantly we have demonstrated that key limitations associated with tissue engineering using multiple cellular aggregates, microtissues or organoids can be alleviated by temporal enzymatic treatment during graft development.

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Integrating melt electrowriting and inkjet bioprinting for engineering structurally organized articular cartilage

Cited by 51 publications

References 70 publications

Articular Cartilage Regeneration through Bioassembling Spherical Micro-Cartilage Building Blocks

Articular Cartilage Regeneration through Bioassembling Spherical Micro-Cartilage Building Blocks

Mechanical and Biological Evaluation of Melt-Electrowritten Polycaprolactone Scaffolds for Acetabular Labrum Restoration

Temporal enzymatic treatment to enhance the remodelling of multiple cartilage microtissues into a structurally organised tissue

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