**1. Introduction**

In vivo animal models are frequently used in orthopedic and trauma research. Due to ethical issues, researchers are focused to replace animal models by establishing novel in vitro systems. However, small tissue fragments are often used in in vitro systems thereby losing tissue's architecture at some times. Although it is possible to use in vitro organ and tissue cultures that allow preservation and

differentiation, the control of dynamic cell properties and simulation of cell interactions remain difficult. In orthopedic and trauma research, the major disadvantages involve the placing of physiological loading and the cellular and molecular orchestration compared to the in vivo system. Hence, animal models are essential not only to evaluate pathological bone but also to study tissue response, biocompatibility and mechanical properties, especially when it comes to implant materials [1].

While small animals (mice and rats) are most commonly used due to lower costs (e.g., purchase, breeding, and housing), easy handling and the feasibility to enlarge the animal number, large animals (sheep and dogs) show several advantages including bone size, body weight, and bone quality when compared to humans. Murine animal models are commonly used to evaluate pathophysiology and novel treatment strategies [2]. For example, mice are highly adaptable to pathological conditions by experimental manipulation. Moreover, molecular tools, antibodies, and the well-characterized mouse strains (including knock-out or transgenic models) make the use of these animals more advantageous [3, 4]. There has been a long debate on whether rodents are appropriate to study osteophysiology due to the lack of true skeletal maturity (e.g., lack of Haversian remodeling and closure of epiphyseal growth plate) [2]. Larger animals, such as sheep and dogs, show several advantages over small models, including their life span and extended phases of skeletally matured bone, but seasonal bone loss and plexiform cortical bone especially occur in sheep. Thus, there is no animal model that entirely fulfills all requirements making it necessary to follow a particular research question and to confirm results obtained in research on small animal models in large animals before entering the clinics.

In this chapter, we will mainly focus on four animal models including mouse, rat, sheep, and dog. Since there are several bone pathologies, which need in vivo research models, we will particularly focus on osteoporosis and osteoarthritis as one of the major bone pathologies that are also associated with implant and scaffold research. Moreover, we will provide an overview about implant research in orthopedics and trauma surgery with specialization on bioresorbable implant technology.
