Tissue engineering scaled-up, anatomically shaped osteochondral constructs for joint resurfacing

The ability to print defined patterns of cells and extracellular-matrix components in three dimensions has enabled the engineering of simple biological tissues, however bioprinting functional solid organs is beyond the capabilities of current biofabrication technologies. An alternative approach would be to bioprint the developmental precursor to an adult organ, using this engineered rudiment as a template for subsequent organogenesis in vivo. Here we demonstrate that developmentally inspired hypertrophic cartilage templates can be engineered in vitro using stem cells within a supporting gamma-irradiated alginate bioink incorporating Arg-Gly-Asp (RGD) adhesion peptides.Furthermore, these soft tissue templates can be reinforced with a network of printed polycaprolactone fibres, resulting in a ~350 fold increase in construct compressive modulus providing the necessary stiffness to implant such immature cartilaginous rudiments into load bearing locations. As a proofof-principal, multiple-tool biofabrication was used to engineer a mechanically reinforced cartilaginous template mimicking the geometry of a vertebral body, which in vivo supported the development of a vascularized bone organ containing trabecular-like endochondral bone with a supporting marrow structure. Such developmental engineering approaches could be applied to the biofabrication of other solid organs by bioprinting pre-cursors that have the capacity to mature into their adult counterparts over time in vivo.3

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“…Statistical analysis was performed as previously described [47] . Briefly tukey's test for multiple comparisons was used to compare conditions.…”

Section: Discussionmentioning

confidence: 99%

3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering

Daly

Cunniffe

Sathy

et al. 2016

Adv Healthcare Materials

224

179

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“…A 3D molding technique was developed to fabricate tissue-engineered large-scale osteochondral constructs (typical size over 2 cm) of alginate hydrogel with anatomical shapes [280]. The fabrication process involved 3D medical imaging of femoral condyle and tibial plateau, modeling, two-part reverse mold design/fabrication, and MSC/chondrocyte-laden alginate/agarose hydrogel construct molding.…”

Section: Advanced Manufacturing Techniques For Engineering Osteochmentioning

confidence: 99%

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

et al. 2017

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Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue engineered artificial matrices that can replace the damaged regions and promote tissue regeneration. Hydrogels are emerging as a promising class of biomaterials for both soft and hard tissue regeneration. Many critical properties of hydrogels, such as mechanical stiffness, elasticity, water content, bioactivity, and degradation, can be rationally designed and conveniently tuned by proper selection of the material and chemistry. Particularly, advances in the development of cell-laden hydrogels have opened up new possibilities for cell therapy. In this article, we describe the problems encountered in this field and review recent progress in designing cell-hydrogel hybrid constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel type, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation matrices with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing technologies (e.g. molding, bioprinting, and assembly) for fabrication of hydrogel-based osteochondral and cartilage constructs with complex compositions and microarchitectures to mimic their native counterparts.

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“…BMSCs are an attractive option, but their propensity for osteogenesis limits their use for meniscal tissue engineering (Makris, Hadidi, & Athanasiou, 2011;Van der Bracht, Verdonk, Verbruggen, Elewaut, & Verdonk, 2007). We have demonstrated that infrapatellar fat pad-derived stem cells (FPSCs) represent an attractive alternative to BMSCs for engineering of cartilaginous tissues (Buckley et al, 2010;Carroll, Buckley, & Kelly, 2014;Luo, O'Reilly, Thorpe, Buckley, & Kelly, 2016;Mesallati, Sheehy, Vinardell, Buckley, & Kelly, 2015;Vinardell, Sheehy, Buckley, & Kelly, 2012). In terms of instructive cues, a number of growth factors (GFs), hormones, and other small molecules are known to influence the development and regeneration of meniscal tissue.…”

mentioning

confidence: 99%

Meniscus ECM‐functionalised hydrogels containing infrapatellar fat pad‐derived stem cells for bioprinting of regionally defined meniscal tissue

Romanazzo

Vedicherla

Moran

et al. 2017

J Tissue Eng Regen Med

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Injuries to the meniscus of the knee commonly lead to osteoarthritis. Current therapies for meniscus regeneration, including meniscectomies and scaffold implantation, fail to achieve complete functional regeneration of the tissue. This has led to increased interest in cell and gene therapies and tissue engineering approaches to meniscus regeneration. The implantation of a biomimetic implant, incorporating cells, growth factors, and extracellular matrix (ECM)-derived proteins, represents a promising approach to functional meniscus regeneration. The objective of this study was to develop a range of ECM-functionalised bioinks suitable for 3D bioprinting of meniscal tissue. To this end, alginate hydrogels were functionalised with ECM derived from the inner and outer regions of the meniscus and loaded with infrapatellar fat pad-derived stem cells. In the absence of exogenously supplied growth factors, inner meniscus ECM promoted chondrogenesis of fat pad-derived stem cells, whereas outer meniscus ECM promoted a more elongated cell morphology and the development of a more fibroblastic phenotype. With exogenous growth factors supplementation, a more fibrogenic phenotype was observed in outer ECM-functionalised hydrogels supplemented with connective tissue growth factor, whereas inner ECM-functionalised hydrogels supplemented with TGFβ3 supported the highest levels of Sox-9 and type II collagen gene expression and sulfated glycosaminoglycans (sGAG) deposition. The final phase of the study demonstrated the printability of these ECM-functionalised hydrogels, demonstrating that their codeposition with polycaprolactone microfibres dramatically improved the mechanical properties of the 3D bioprinted constructs with no noticeable loss in cell viability. These bioprinted constructs represent an exciting new approach to tissue engineering of functional meniscal grafts.

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Tissue engineering scaled-up, anatomically shaped osteochondral constructs for joint resurfacing

Cited by 39 publications

References 49 publications

3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering

3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

Meniscus ECM‐functionalised hydrogels containing infrapatellar fat pad‐derived stem cells for bioprinting of regionally defined meniscal tissue

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