Long Bone Defect Models for Tissue Engineering Applications: Criteria for Choice

Abstract

The replacement and repair of bone lost due to trauma, cancer, or congenital defects is a major clinical challenge. Skeletal tissue engineering is a potentially powerful strategy in modern regenerative medicine, and research in this field has increased greatly in recent years. Tissue engineering strategies seek to translate research findings in the fields of materials science, stem cell biology, and biomineralization into clinical applications, demanding the use of appropriate in vivo models to investigate bone regeneration of the long bone. However, identification of the optimal in vivo segmental bone defect model from the literature is difficult due to the use of different animal species (large and small mammals), different bones (weight-bearing and nonweight bearing), and multiple protocols, including the use of various scaffolds, cells, and bioactives. The aim of this review is to summarize the available animal models for evaluating long bone regeneration in vivo. We highlight the differences not only in species and sites but also in defect size, means of defect creation, duration of study, and fixation method. A critical evaluation of the most clinically relevant models is addressed to guide the researcher in his/her choice of the most appropriate model to use in future hypothesis-driven investigations.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…The first determinant depends on the availability of an animal model that mimics a human disease involving bone repair so that the data generated can be used to predict the drug efficacy and safety in patients. Examples of animal models with good predictability of clinical outcomes include models of postmenopausal osteoporosis [87][88][89][90][91][92], models of glucocorticoid induced bone loss [93][94][95][96], models of cancer metastasis to bone [97], disuse models [98,99], fracture healing models [100][101][102][103] and several others. The second determinant of successful experimentation relates to translational biomarkers of novel therapy efficacy and safety that can be accurately predicted and monitored in patients.…”

Bone tissue engineering by using a combination of polymer/Bioglass composites with human adipose-derived stem cells

“…Traditionally, small defects are covered using autologous bone taken from iliac crest or ribs but large bony defects require autografts or allografts whose application is limited in terms of material availability and successful tissue in-growth (Eppley et al 2005). Furthermore, allografts carry the risk of disease transmission and host immune response (Horner et al 2010; Saha et al 2011;Yang et al 2006). In contrast, xenografts are in plentiful supply but they carry even greater risks of immune rejection and in situ degeneration as well as disease transmission.…”

The effect of mechanical loading on osteogenesis of human dental pulp stromal cells in a novel in vitro model

“…Current clinical therapies to alveolar bone loss are limited in using artificial bone substitutes and autogenic and allogenic bone grafts (Canter et al 2007;Felix Lanao et al 2012;Zietek et al 2008). However, a number of limitations of using these conventional methods have led to the search for alternative approaches such as stem cell therapy and tissue engineering to tackle this clinical challenge (Green et al 2004;Gu et al 1997;Horner et al 2010;Horner et al 2008;Yang et al 2004;Yang et al 2003b). …”