Individual response variations in scaffold-guided bone regeneration are determined by independent strain- and injury-induced mechanisms

Reznikov, Natalie; Boughton, Oliver; Ghouse, Shaaz; Weston, Anne; Collinson, Lucy M.; Blunn, Gordon; Jeffers, Jonathan R.T.; Cobb, Justin P.; Stevens, Molly M.

doi:10.1016/j.biomaterials.2018.11.026

Cited by 68 publications

(69 citation statements)

References 56 publications

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“…The implant modulus depends on pore size and strut thickness, whilst the amount of bone ingrowth depends on implant modulus and loading conditions. The reliance of bone ingrowth on the modulus of a porous material has been demonstrated, 8,24 and from this study it is apparent that modulus mismatch between the implant and the surrounding bone may lead to regions of the porous structure without bone tissue. The novelty of our study is that we predict bone ingrowth and relate this to the fatigue performance of substantially porous implants.…”

Section: Discussionmentioning

confidence: 63%

Partial Bone Formation in Additive Manufactured Porous Implants Reduces Predicted Stress and Danger of Fatigue Failure

et al. 2019

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New porous implant designs made possible by additive manufacturing allow for increased osseointegration, potentially improving implant performance and longevity for patients that require massive bone implants. The aim of this study was to evaluate how implantation and the strain distribution in the implant affect the pattern of bone ingrowth and how changes in tissue density within the pores alter the stresses in implants. The hypothesis was that porous metal implants are susceptible to fatigue failure, and that this reduces as osteointegration occurs. A phenomenological, finite element analysis (FEA) bone remodelling model was used to predict partial bone formation for two porous (pore sizes of 700 μm and 1500 μm), laser sintered Ti6Al4V implants in an ovine condylar defect model, and was compared and verified against in vivo, histology results. The FEA models predicted partial bone formation within the porous implants, but over-estimated the amount of bone-surface area compared to histology results. The stress and strain in the implant and adjacent tissues were assessed before, during bone remodelling, and at equilibrium. Results showed that partial bone formation improves the stress distribution locally by reducing stress concentrations for both pore sizes, by at least 20%. This improves the long-term fatigue resistance for the larger pore implant, as excessively high stress is reduced to safer levels (86% of fatigue strength) as bone forms. The stress distribution only changed slightly in regions without bone growth. As the extent of bone formation into extensively porous bone implants depends on the level of stress shielding, the design of the implant and stiffness have significant influence on bone integration and need to be considered carefully to ensure the safety of implants with substantial porous regions. To our knowledge this is the first time that the effect of bone formation on stress distribution within a porous implant has been described and characterised.

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Section: Discussionmentioning

confidence: 63%

Partial Bone Formation in Additive Manufactured Porous Implants Reduces Predicted Stress and Danger of Fatigue Failure

et al. 2019

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“…28 The defined structure, as a kind of mechanical cue, can influence cell behaviors and control some of their key features at the molecular and cellular levels. 7,12 When fabricating bone substitute scaffolds, we need to consider the impact of physical cues such as internal porosity, 7 pore structure, surface roughness, compressive moduli, 29 and the alignment of ECM and bone cells. 30 Various methods have been applied to prepare 3D porous biomaterial scaffolds as bone substitutes.…”

Section: Fabrication Of Three-dimensional Biomaterials Scaffolds For Bmentioning

confidence: 99%

Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

2020

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Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an innate capacity to heal from damage. However, massive bone defects due to traumatic injury, tumor resection, or congenital diseases pose a great challenge to reconstructive surgery. Scaffold-based tissue engineering (TE) is a promising strategy for bone regenerative medicine, because biomaterial scaffolds show advanced mechanical properties and a good degradation profile, as well as the feasibility of controlled release of growth and differentiation factors or immobilizing them on the material surface. Additionally, the defined structure of biomaterial scaffolds, as a kind of mechanical cue, can influence cell behaviors, modulate local microenvironment and control key features at the molecular and cellular levels. Recently, nano/micro-assisted regenerative medicine becomes a promising application of TE for the reconstruction of bone defects. For this reason, it is necessary for us to have in-depth knowledge of the development of novel nano/micro-based biomaterial scaffolds. Thus, we herein review the hierarchical structure of bone, and the potential application of nano/micro technologies to guide the design of novel biomaterial structures for bone repair and regeneration.

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“…The developing field of bone engineering aims to take advantage of the innate repair capacity of this tissue (O'Brien, 2011), but the variability in the outcome of the products is one of the main limitations for their clinical translation. For example, the individual heterogeneous response in newly formed bone tissue formation leads to drastic changes in the scaffold design (Reznikov et al, 2019). In vitro models can explore the impact of individual response in tissue engineering products, but they require a bone cell source representing the phenotype variability.…”

Section: Introductionmentioning

confidence: 99%

Primary Human Osteoblasts Cultured in a 3D Microenvironment Create a Unique Representative Model of Their Differentiation Into Osteocytes

Nasello

Alamán‐Díez

Schiavi

et al. 2020

Front. Bioeng. Biotechnol.

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Microengineered systems provide an in vitro strategy to explore the variability of individual patient response to tissue engineering products, since they prefer the use of primary cell sources representing the phenotype variability. Traditional in vitro systems already showed that primary human osteoblasts embedded in a 3D fibrous collagen matrix differentiate into osteocytes under specific conditions. Here, we hypothesized that translating this environment to the organ-on-a-chip scale creates a minimal functional unit to recapitulate osteoblast maturation toward osteocytes and matrix mineralization. Primary human osteoblasts were seeded in a type I collagen hydrogel, to establish the role of lower (2.5 × 10 5 cells/ml) and higher (1 × 10 6 cells/ml) cell density on their differentiation into osteocytes. A custom semi-automatic image analysis software was used to extract quantitative data on cellular morphology from brightfield images. The results are showing that cells cultured at a high density increase dendrite length over time, stop proliferating, exhibit dendritic morphology, upregulate alkaline phosphatase (ALP) activity, and express the osteocyte marker dental matrix protein 1 (DMP1). On the contrary, cells cultured at lower density proliferate over time, do not upregulate ALP and express the osteoblast marker bone sialoprotein 2 (BSP2) at all timepoints. Our work reveals that microengineered systems create unique conditions to capture the major aspects of osteoblast differentiation into osteocytes with a limited number of cells. We propose that the microengineered approach is a functional strategy to create a patient-specific bone tissue model and investigate the individual osteogenic potential of the patient bone cells.

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Individual response variations in scaffold-guided bone regeneration are determined by independent strain- and injury-induced mechanisms

Cited by 68 publications

References 56 publications

Partial Bone Formation in Additive Manufactured Porous Implants Reduces Predicted Stress and Danger of Fatigue Failure

Partial Bone Formation in Additive Manufactured Porous Implants Reduces Predicted Stress and Danger of Fatigue Failure

Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

Primary Human Osteoblasts Cultured in a 3D Microenvironment Create a Unique Representative Model of Their Differentiation Into Osteocytes

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