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      The effect of nodal connectivity and strut density within stochastic titanium scaffolds on osteogenesis

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          Abstract

          Modern orthopaedic implants use lattice structures that act as 3D scaffolds to enhance bone growth into and around implants. Stochastic scaffolds are of particular interest as they mimic the architecture of trabecular bone and can combine isotropic properties and adjustable structure. The existing research mainly concentrates on controlling the mechanical and biological performance of periodic lattices by adjusting pore size and shape. Still, less is known on how we can control the performance of stochastic lattices through their design parameters: nodal connectivity, strut density and strut thickness. To elucidate this, four lattice structures were evaluated with varied strut densities and connectivity, hence different local geometry and mechanical properties: low apparent modulus, high apparent modulus, and two with near-identical modulus. Pre-osteoblast murine cells were seeded on scaffolds and cultured in vitro for 28 days. Cell adhesion, proliferation and differentiation were evaluated. Additionally, the expression levels of key osteogenic biomarkers were used to assess the effect of each design parameter on the quality of newly formed tissue. The main finding was that increasing connectivity increased the rate of osteoblast maturation, tissue formation and mineralisation. In detail, doubling the connectivity, over fixed strut density, increased collagen type-I by 140%, increased osteopontin by 130% and osteocalcin by 110%. This was attributed to the increased number of acute angles formed by the numerous connected struts, which facilitated the organization of cells and accelerated the cell cycle. Overall, increasing connectivity and adjusting strut density is a novel technique to design stochastic structures which combine a broad range of biomimetic properties and rapid ossification.

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          Porosity of 3D biomaterial scaffolds and osteogenesis.

          Porosity and pore size of biomaterial scaffolds play a critical role in bone formation in vitro and in vivo. This review explores the state of knowledge regarding the relationship between porosity and pore size of biomaterials used for bone regeneration. The effect of these morphological features on osteogenesis in vitro and in vivo, as well as relationships to mechanical properties of the scaffolds, are addressed. In vitro, lower porosity stimulates osteogenesis by suppressing cell proliferation and forcing cell aggregation. In contrast, in vivo, higher porosity and pore size result in greater bone ingrowth, a conclusion that is supported by the absence of reports that show enhanced osteogenic outcomes for scaffolds with low void volumes. However, this trend results in diminished mechanical properties, thereby setting an upper functional limit for pore size and porosity. Thus, a balance must be reached depending on the repair, rate of remodeling and rate of degradation of the scaffold material. Based on early studies, the minimum requirement for pore size is considered to be approximately 100 microm due to cell size, migration requirements and transport. However, pore sizes >300 microm are recommended, due to enhanced new bone formation and the formation of capillaries. Because of vascularization, pore size has been shown to affect the progression of osteogenesis. Small pores favored hypoxic conditions and induced osteochondral formation before osteogenesis, while large pores, that are well-vascularized, lead to direct osteogenesis (without preceding cartilage formation). Gradients in pore sizes are recommended for future studies focused on the formation of multiple tissues and tissue interfaces. New fabrication techniques, such as solid-free form fabrication, can potentially be used to generate scaffolds with morphological and mechanical properties more selectively designed to meet the specificity of bone-repair needs.
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            Local force and geometry sensing regulate cell functions.

            The shapes of eukaryotic cells and ultimately the organisms that they form are defined by cycles of mechanosensing, mechanotransduction and mechanoresponse. Local sensing of force or geometry is transduced into biochemical signals that result in cell responses even for complex mechanical parameters such as substrate rigidity and cell-level form. These responses regulate cell growth, differentiation, shape changes and cell death. Recent tissue scaffolds that have been engineered at the micro- and nanoscale level now enable better dissection of the mechanosensing, transduction and response mechanisms.
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              Osteoinduction, osteoconduction and osseointegration.

              Osteoinduction is the process by which osteogenesis is induced. It is a phenomenon regularly seen in any type of bone healing process. Osteoinduction implies the recruitment of immature cells and the stimulation of these cells to develop into preosteoblasts. In a bone healing situation such as a fracture, the majority of bone healing is dependent on osteoinduction. Osteoconduction means that bone grows on a surface. This phenomenon is regularly seen in the case of bone implants. Implant materials of low biocompatibility such as copper, silver and bone cement shows little or no osteoconduction. Osseointegration is the stable anchorage of an implant achieved by direct bone-to-implant contact. In craniofacial implantology, this mode of anchorage is the only one for which high success rates have been reported. Osseointegration is possible in other parts of the body, but its importance for the anchorage of major arthroplasties is under debate. Ingrowth of bone in a porous-coated prosthesis may or may not represent osseointegration.
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                Author and article information

                Contributors
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                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                29 November 2023
                2023
                : 11
                : 1305936
                Affiliations
                [1] 1 Department of Mechanical Engineering , Imperial College London , London, United Kingdom
                [2] 2 Centre for Bio Inspired Technology , Department of Electrical and Electronic Engineering , Imperial College London , London, United Kingdom
                [3] 3 Department of Surgery and Cancer , Imperial College London , London, United Kingdom
                [4] 4 Department of Infectious Disease , Imperial College London , London, United Kingdom
                Author notes

                Edited by: Saeed Khademzadeh, Research Institutes of Sweden (RISE), Sweden

                Reviewed by: Paola Ginestra, University of Brescia, Italy

                Dejian Li, Fudan University Pudong Medical Center, China

                Jacobo Paredes, University of California, Berkeley, United States

                *Correspondence: Stylianos Kechagias, s.kechagias20@ 123456imperial.ac.uk ; Jonathan R. T. Jeffers, j.jeffers@ 123456imperial.ac.uk
                [ † ]

                These authors have contributed equally to this work and share third authorship

                Article
                1305936
                10.3389/fbioe.2023.1305936
                10721980
                38107615
                b2314a39-3888-48d4-ac0e-eca58ebb7f87
                Copyright © 2023 Kechagias, Theodoridis, Broomfield, Malpartida-Cardenas, Reid, Georgiou, van Arkel and Jeffers.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 October 2023
                : 20 November 2023
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Institute for Health Research (NIHR300013) and Engineering and Physical Sciences Research Council (EP/R042721/1 and EP/S022546/1).
                Categories
                Bioengineering and Biotechnology
                Original Research
                Custom metadata
                Biofabrication

                additive manufacturing,orthopaedic implants,bone scaffolds,trabecular bone,3d cell culture,osteoblast differentiation

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