Scaffold channel size influences stem cell differentiation pathway in 3-D printed silica hybrid scaffolds for cartilage regeneration

S, Li; Tallia, Francesca; Aa, Mohammed; Stevens, Molly M.; Jones, Julian R.

doi:10.1039/c9bm01829h

Cited by 42 publications

(43 citation statements)

References 50 publications

(68 reference statements)

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“…For this study, a w/w ratio of 25:75 (inorganic:organic) was utilised. The ink was 3D printed using robocasting to produce scaffolds with strut diameters of 140–200 µm, vertical channel size of 200–250 µm [ 25 ] and modal interconnect size of 130 ± 10 µm [ 24 ]. The localised strain mechanics were considered for implants of two sizes: cubic “Mech” implants of 5.5 mm edge length typically used for materials testing ( n = 2, Figure 1 a) and cylindrical “Imp” implants of dimensions similar to the intended tissue engineering application for use in animal models during device development: 5 mm diameter and 1.2 mm height ( n = 4, Figure 1 b).…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we implemented laboratory micro-CT and DVC to develop a mechanical testing methodology to evaluate 3D performance of low-stiffness degradable scaffolds for articular cartilage regeneration. We chose 3D-printed inorganic sol-gel hybrids for this study due to their ability to take cyclic load, their fully degradable nature, their tailorable mechanical properties, which are similar to that of the articular cartilage tissue [ 24 ] and evidence that, when printed with pore channel sizes of 200–250 µm, human mesenchymal stem cells were sent down a chondrogenic lineage and stimulated to produce articular-like cartilage matrix in vitro [ 25 ]. These sol-gel hybrids therefore make an ideal implant choice to test the capabilities of DVC for regenerative medicine applications.…”

Section: Introductionmentioning

confidence: 99%

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Quantifying 3D Strain in Scaffold Implants for Regenerative Medicine

et al. 2020

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Regenerative medicine solutions require thoughtful design to elicit the intended biological response. This includes the biomechanical stimulus to generate an appropriate strain in the scaffold and surrounding tissue to drive cell lineage to the desired tissue. To provide appropriate strain on a local level, new generations of scaffolds often involve anisotropic spatially graded mechanical properties that cannot be characterised with traditional materials testing equipment. Volumetric examination is possible with three-dimensional (3D) imaging, in situ loading and digital volume correlation (DVC). Micro-CT and DVC were utilised in this study on two sizes of 3D-printed inorganic/organic hybrid scaffolds (n = 2 and n = 4) with a repeating homogenous structure intended for cartilage regeneration. Deformation was observed with a spatial resolution of under 200 µm whilst maintaining displacement random errors of 0.97 µm, strain systematic errors of 0.17% and strain random errors of 0.031%. Digital image correlation (DIC) provided an analysis of the external surfaces whilst DVC enabled localised strain concentrations to be examined throughout the full 3D volume. Strain values derived using DVC correlated well against manually calculated ground-truth measurements (R2 = 0.98, n = 8). The technique ensures the full 3D micro-mechanical environment experienced by cells is intimately considered, enabling future studies to further examine scaffold designs for regenerative medicine.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantifying 3D Strain in Scaffold Implants for Regenerative Medicine

et al. 2020

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“…This was carried out following six weeks of implantation within an ovine model, a typical study length and model choice for articular cartilage device research [ 23 ]. The 3D printed hybrid scaffold implant was specifically chosen as the implanted regenerative medicine device because of its ability to take cyclic load, tailorable mechanical properties which in this instance were similar to that of the articular cartilage tissue [ 24 ], the fully-degradable nature over a period of months and evidence that, when printed with pore channel sizes of 200–250 µm, human mesenchymal stem cells were sent down a chondrogenic lineage and stimulated to produce articular-like cartilage matrix in vitro [ 25 ]. Analysis was carried out using in situ micro-CT mechanical testing and DVC on an explanted tissue-biomaterial sample (n = 1) including newly formed tissue.…”

Section: Introductionmentioning

confidence: 99%

Exploratory Full-Field Mechanical Analysis across the Osteochondral Tissue—Biomaterial Interface in an Ovine Model

et al. 2020

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Osteochondral injuries are increasingly prevalent, yet success in articular cartilage regeneration remains elusive, necessitating the development of new surgical interventions and novel medical devices. As part of device development, animal models are an important milestone in illustrating functionality of novel implants. Inspection of the tissue-biomaterial system is vital to understand and predict load-sharing capacity, fixation mechanics and micromotion, none of which are directly captured by traditional post-mortem techniques. This study aims to characterize the localised mechanics of an ex vivo ovine osteochondral tissue–biomaterial system extracted following six weeks in vivo testing, utilising laboratory micro-computed tomography, in situ loading and digital volume correlation. Herein, the full-field displacement and strain distributions were visualised across the interface of the system components, including newly formed tissue. The results from this exploratory study suggest that implant micromotion in respect to the surrounding tissue could be visualised in 3D across multiple loading steps. The methodology provides a non-destructive means to assess device performance holistically, informing device design to improve osteochondral regeneration strategies.

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“…Likewise, more sophisticated models of the electromechanobiology of cells and tissues need to be found to eventually predict the deformation or displacement of cells in their native environment [ 67 ]. Such models could then explain, for example, why and how a certain channel size in printed scaffolds influences the cell shape [ 68 ]. Eventually, an optimal channel width should be determined to promote chondrogenesis, which goes along with spherical cell shape.…”

Section: Resultsmentioning

confidence: 99%

Numerical Simulations as Means for Tailoring Electrically Conductive Hydrogels towards Cartilage Tissue Engineering by Electrical Stimulation

et al. 2020

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Cartilage regeneration is a clinical challenge. In recent years, hydrogels have emerged as implantable scaffolds in cartilage tissue engineering. Similarly, electrical stimulation has been employed to improve matrix synthesis of cartilage cells, and thus to foster engineering and regeneration of cartilage tissue. The combination of hydrogels and electrical stimulation may pave the way for new clinical treatment of cartilage lesions. To find the optimal electric properties of hydrogels, theoretical considerations and corresponding numerical simulations are needed to identify well-suited initial parameters for experimental studies. We present the theoretical analysis of a hydrogel in a frequently used electrical stimulation device for cartilage regeneration and tissue engineering. By means of equivalent circuits, finite element analysis, and uncertainty quantification, we elucidate the influence of the geometric and dielectric properties of cell-seeded hydrogels on the capacitive-coupling electrical field stimulation. Moreover, we discuss the possibility of cellular organisation inside the hydrogel due to forces generated by the external electric field. The introduced methodology is easily reusable by other researchers and allows to directly develop novel electrical stimulation study designs. Thus, this study paves the way for the design of future experimental studies using electrically conductive hydrogels and electrical stimulation for tissue engineering.

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Scaffold channel size influences stem cell differentiation pathway in 3-D printed silica hybrid scaffolds for cartilage regeneration

Abstract: We report that 3-D printed scaffold channel size can direct bone marrow derived stem cell differentiation, e.g. ∼200–250 μm channels promote hyaline-like cartilage matrix production.

Cited by 42 publications

References 50 publications

Quantifying 3D Strain in Scaffold Implants for Regenerative Medicine

Quantifying 3D Strain in Scaffold Implants for Regenerative Medicine

Exploratory Full-Field Mechanical Analysis across the Osteochondral Tissue—Biomaterial Interface in an Ovine Model

Numerical Simulations as Means for Tailoring Electrically Conductive Hydrogels towards Cartilage Tissue Engineering by Electrical Stimulation

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