Gene Delivery of TGF-β3 and BMP2 in an MSC-Laden Alginate Hydrogel for Articular Cartilage and Endochondral Bone Tissue Engineering

Gonzalez-Fernandez, Tomas; Tierney, Erica G.; Cunniffe, Gráinne M.; O’Brien, Fergal J.; Kelly, Daniel J.

doi:10.1089/ten.tea.2015.0576

Cited by 120 publications

(98 citation statements)

References 58 publications

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“…For example, a gene delivery platform of TGF- β 3 and BMP- 2 in alginate hydrogels has been developed for cartilage and osteochondral tissue [268]. The results indicated that sustained overexpression of the transgenes were achieved with nano-hydroxyapatite (nHAp) plasmid DNA (pDNA) encoding.…”

Section: Effects Of Growth Factors and Delivery Methods On Chondromentioning

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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Section: Effects Of Growth Factors and Delivery Methods On Chondromentioning

confidence: 99%

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

et al. 2017

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“…CaP based biomaterials, including α and β-TCP, hydroxyapatite (HA) and calcium sulphate, have been extensively used in orthopaedics as a bone substitute material 26,53,54 . Nanoparticles in a size range of 20-200 nm has been shown to be optimal for intracellular delivery, with bare CaP nanoparticles often undergoing significant levels of agglomeration leading to development of a much larger particle size over time [55][56][57][58] . Thus, currently CaP nanoparticles are largely used with modifications to increase their stability and to control their size in order to improve their capacity to cross the cell membrane 57 .…”

Section: Discussionmentioning

confidence: 99%

RALA complexed α-TCP nanoparticle delivery to mesenchymal stem cells induces bone formation in tissue engineered constructs in vitro and in vivo

et al. 2017

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A range of bone regeneration strategies, from growth factor delivery and/or mesenchymal stem cell (MSC) transplantation to endochondral tissue engineering, have been developed in recent years. Despite their tremendous promise, the clinical translation and future use of many of these strategies is being hampered by concerns such as off target effects associated with growth factor delivery. Therefore the overall objective of this study was to investigate the influence of alpha-tricalcium phosphate (α-TCP) nanoparticle delivery into MSCs using a RALA cell penetrating peptide on osteogenesis in vitro and both intramembranous and endochondral bone formation in vivo. RALA conjugated α-TCP nanoparticle delivery to MSCs resulted in an increased expression of bone morphogenetic protein-2 (BMP-2) and an upregulation in a number of key osteogenic genes. When α-TCP stimulated MSCs were encapsulated into alginate hydrogels, enhanced mineralization of the engineered construct was observed over a 28 day culture period. Furthermore, the in vivo bone forming potential of RALA conjugated α-TCP nanoparticle delivery to MSCs was found to be comparable to growth factor delivery. Recognizing the potential and limitations associated with endochondral bone tissue engineering strategies, we then sought to explore how α-TCP nanoparticle delivery to MSCs influences early mineralization of engineered cartilage templates in vitro and their subsequent ossification in vivo. Despite accelerating mineralization of engineered cartilage templates in vitro, RALA conjugated α-TCP nanoparticle delivery did not enhance endochondral bone formation in vivo. Therefore the potential of RALA conjugated α-TCP nanoparticle delivery appears to be as an alternative to growth factor delivery as a single stage strategy for promoting bone generation.3

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“…[4] Alternative cell types, including bone marrow (MSCs) and adipose derived stem cells (ASCs), also have been the subject of extensive research for cartilage tissue engineering. [5] …”

Section: Introductionmentioning

confidence: 99%

Composite Cellularized Structures Created from an Interpenetrating Polymer Network Hydrogel Reinforced by a 3D Woven Scaffold

Moffat

Goon

Moutos

et al. 2018

Macromolecular Bioscience

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Biomaterial scaffolds play multiple roles in cartilage tissue engineering, including controlling architecture of newly formed tissue while facilitating growth of embedded cells and simultaneously providing functional properties to withstand the mechanical environment within the native joint. In particular, hydrogels-with high water content and desirable transport properties-while highly conducive to chondrogenesis, often lack functional mechanical properties. In this regard, interpenetrating polymer network (IPN) hydrogels can provide mechanical toughness greatly exceeding that of individual components; however, many IPN materials are not biocompatible for cell encapsulation. In this study, an agarose and poly(ethylene) glycol IPN hydrogel is seeded with human mesenchymal stem cells (MSCs). Results show high viability of MSCs within the IPN hydrogel, with improved mechanical properties compared to constructs comprised of individual components. These properties are further strengthened by integrating the hydrogel with a 3D woven structure. The resulting fiber-reinforced hydrogels display functional macroscopic mechanical properties mimicking those of native articular cartilage, while providing a local microenvironment that supports cellular viability and function. These findings suggest that a fiber-reinforced IPN hydrogel can support stem cell chondrogenesis while allowing for significantly enhanced, complex mechanical properties at multiple scales as compared to individual hydrogel or fiber components.

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Gene Delivery of TGF-β3 and BMP2 in an MSC-Laden Alginate Hydrogel for Articular Cartilage and Endochondral Bone Tissue Engineering

Cited by 120 publications

References 58 publications

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

RALA complexed α-TCP nanoparticle delivery to mesenchymal stem cells induces bone formation in tissue engineered constructs in vitro and in vivo

Composite Cellularized Structures Created from an Interpenetrating Polymer Network Hydrogel Reinforced by a 3D Woven Scaffold

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