Traditionally, bioactive glasses have been used to fill and restore bone defects. More recently, this category of biomaterials has become an emerging research field for bone tissue engineering applications. Here, we review and discuss current knowledge on porous bone tissue engineering scaffolds on the basis of melt-derived bioactive silicate glass compositions and relevant composite structures. Starting with an excerpt on the history of bioactive glasses, as well as on fundamental requirements for bone tissue engineering scaffolds, a detailed overview on recent developments of bioactive glass and glass-ceramic scaffolds will be given, including a summary of common fabrication methods and a discussion on the microstructural-mechanical properties of scaffolds in relation to human bone (structure-property and structure-function relationship). In addition, ion release effects of bioactive glasses concerning osteogenic and angiogenic responses are addressed. Finally, areas of future research are highlighted in this review.

https://pure.tue.nl/ws/files/3034662/Metis245608.pdf

Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering

The field of tissue engineering continues to advance with the discovery of new biomaterials, growth factors and scaffold fabrication techniques. However, for the ultimate success of a tissue engineered construct the issue of nutrient transport to the scaffold interior needs to be addressed. Often, the requirements for adequate nutrient supply are at odds with other scaffold design parameters such as mechanical properties as well as scaffold fabrication techniques, leading to incongruities in finding optimal solutions. The goal of this review article is to provide an overview of the various engineering design factors that promote movement of nutrients, waste and other biomolecules in scaffolds for musculoskeletal tissue engineering applications. The importance of diffusion in scaffolds and how it is influenced by porosity, permeability, architecture, and nutrient mixing has been emphasized. Methods for measuring porosity and permeability have also been outlined. The different types of biomaterials used, scaffold fabrication techniques implemented and the pore sizes/porosities obtained over the past 5 years have also been addressed.

Diffusion in musculoskeletal tissue engineering scaffolds: design issues related to porosity, permeability, architecture, and nutrient mixing.

Bone marrow mesenchymal stem cells (MSCs) are multipotent cells, which among other cell lineages, give rise to adipocytes and osteoblasts. Within the bone marrow, the differentiation of MSCs into adipocytes or osteoblasts is competitively balanced; mechanisms that promote one cell fate actively suppress mechanisms that induce the alternative lineage. This occurs through the cross talk between complex signaling pathways including those derived from bone morphogenic proteins (BMPs), winglesstype MMTV integration site (Wnt) proteins, hedgehogs, delta/jagged proteins, fibroblastic growth factors (FGF), insulin, insulin-like growth factors (IGF), and transcriptional regulators of adipocyte and osteoblast differentiation including peroxisome proliferator-activated receptor-γ (PPARγ) and runt-related transcription factor 2 (Runx2). Here, we discuss the molecular regulation of bone marrow adipogenesis with emphasis on signals that interact with osteoblastogenic pathways and highlight the possible therapeutic implications of these interactions.

Adipocyte differentiation of bone marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jps.22257

A review of three‐dimensional in vitro tissue models for drug discovery and transport studies

Tissue engineering is an interdisciplinary field that combines the knowledge and technology of cells, engineering materials, and suitable biochemical factor to create artificial organs and tissues, or to regenerate damage tissues (Langer & Vacanti, 1993). It involves cell seeding on a scaffold followed by culturing in vitro prior to implantation in vivo. The ideal scaffolds provide a framework and initial support for the cells to attach, proliferate and differentiate, and form an extracellular matrix (ECM) (Agrawal & Ray, 2001). It should be noted that scaffold surface topography and chemistry (wettability, softness and stiffness, roughness); microstructure (porosity, pore size, pore shape, interconnectivity, specific surface area) (O'Brien & Gibson, 2005b) and mechanical properties (Engler & Discher, 2006; Peyton & Putnam, 2005) have been shown to significantly influence cell behaviors such as adhesion, growth and differentiation, and to affect the bioactivity of scaffolds used for in vivo regeneration applications of various tissues, such as cartilage, skin and peripheral nerves. For tissue engineering purposes, understanding cell behavior and responses on extracellular scaffolds within physiological relevant 3D construct can aid the design of optimal bioactive tissue engineering scaffolds. Controlling cell behavior and remodeling by modulating the local engineered extracellular environment process is also a critical step in the development of the next generation of bioactive tissue engineering scaffolds. The present chapter will discuss cell responses to surface chemistry and various architecture parameters; current approaches and technologies to optimize tissue engineering scaffolds and challenges in studying the cell interaction with scaffolds.

/pdf/cell-responses-to-surface-and-architecture-of-tissue-2fhut5qpgj.pdf

Cell Responses to Surface and Architecture of Tissue Engineering Scaffolds

The classic paradigm for in vitro tissue engineering of bone involves the isolation and culture of donor osteoblasts or osteoprogenitor cells within three-dimensional (3D) scaffold biomaterials under conditions that support tissue growth and mineralized osteoid formation. Our studies focus on the development and utilization of new dynamic culture technologies to provide adequate nutrient flux within 3D scaffolds to support ongoing tissue formation. In this study, we have developed a basic one-dimensional (1D) model to characterize the efficiency of passive nutrient diffusion and transport flux to bone cells within 3D scaffolds under static and dynamic culture conditions. Internal fluid perfusion within modeled scaffolds increased rapidly with increasing pore volume and pore diameter to a maximum of approximately 1% of external fluid flow. In contrast, internal perfusion decreased significantly with increasing pore channel tortuosity. Calculations of associated nutrient flux indicate that static 3D culture and some inappropriately designed dynamic culture environments lead to regions of insufficient nutrient concentration to maintain cell viability, and can result in steep nutrient concentration gradients within the modeled constructs. These quantitative studies provide a basis for development of new dynamic culture methodologies to overcome the limitations of passive nutrient diffusion in 3D cell-scaffold composite systems proposed for in vitro tissue engineering of bone.

/pdf/tissue-engineered-bone-measurement-of-nutrient-transport-in-4at5w2yzyh.pdf

Tissue engineered bone: Measurement of nutrient transport in three‐dimensional matrices

Fibroblast Growth Factor 2 Induced Proliferation in Osteoblasts and Bone Marrow Stromal Cells: A Whole Cell Model

The PR2OVE-IT (Peer Reviewed Research Offering Validation of Effective and Innovative Teaching) website (www.pr2ove-it.org) is a database that summarizes the available research on educational interventions designed to enhance student learning, retention, and professional success. It is intended to be a tool for translating education research on interventions into practical classroom use by engineering faculty who are not engaged in educational research. The website is divided into two major categories for searching and viewing information about articles: interventions (instructional practices) and outcomes (the main result(s) of the study). The website provides three additional major categories for more refined searching: subject/content area (content or context of the learning environment), study characteristics (basic information about each study), and evaluation (method by which the intervention was assessed). This paper presents the results of an analysis of the 367 articles that were in the database on March 17, 2006.

Melissa A. Dupree

Papers

Tissue engineered bone: Measurement of nutrient transport in three‐dimensional matrices

Fibroblast Growth Factor 2 Induced Proliferation in Osteoblasts and Bone Marrow Stromal Cells: A Whole Cell Model

An Analysis of the Engineering Education Research Base on Interventions