Animal models of impaired long bone healing and tissue engineering‐ and cell‐based in vivo interventions

Abstract

Bone healing after injury typically follows a systematic process and occurs spontaneously under appropriate physiological conditions. However, impaired long bone healing is still quite common and may require surgical intervention. Various complications can result in different forms of impaired bone healing including nonunion, critical‐size defects, or stress fractures. While a nonunion may occur due to impaired biological signaling and/or mechanical instability, a critical‐size defect exhibits extensive bone loss that will not spontaneously heal. Comparatively, a stress fracture occurs from repetitive forces and results in a non‐healing crack or break in the bone. Clinical standards of treatment vary between these bone defects due to their pathological differences. The use of appropriate animal models for modeling healing defects is critical to improve current treatment methods and develop novel rescue therapies. This review provides an overview of these clinical bone healing impairments and current animal models available to study the defects in vivo. The techniques used to create these models are compared, along with the outcomes, to clarify limitations and future objectives. Finally, rescue techniques focused on tissue engineering and cell‐based therapies currently applied in animal models are specifically discussed to analyze their ability to initiate healing at the defect site, providing information regarding potential future therapies. In summary, this review focuses on the current animal models of nonunion, critical‐size defects, and stress fractures, as well as interventions that have been tested in vivo to provide an overview of the clinical potential and future directions for improving bone healing.

Osseointegration of Tantalum Trabecular Metal in Titanium Dental Implants: Histological and Micro-CT Study

“…Long-term follow-up studies in humans would also be crucial for validating findings from animal models. This could lead to a more comprehensive understanding of bone-implant interactions and ultimately improve the outcomes and lifespan of implant procedures in humans [54].…”

Murine Progeria Model Exhibits Delayed Fracture Healing with Dysregulated Local Immune Response

“…While a variety of preclinical models have been developed, many are associated with limitations as they typically model only a specific cause of delayed healing. The most prevalent models of delayed union in rodents are physically induced via segmental defects, modified fixation stiffness, or additional soft tissue, vascular, or periosteal injury [5,[10][11][12]. These models are useful for screening potential therapeutics that address significant trauma scenarios and investigate how mechanical factors such as weight-bearing and fixation properties influence regeneration.…”

Scaphoid Bone Nonunions: Clinical and Functional Outcomes of Collagen/PGA Scaffolds and Cell-Based Therapy

“…If left untreated, nonunion would lead to further arthritis, most probably within five years after injury, , and this may be a potential condition that disables patients in their early adulthood. Different orthobiologic methods, including tissue engineering, have been proposed for nonunion treatment. − Impregnating live cells in artificial or biological matrices/sponges/scaffolds is considered a promising bone regeneration approach, as it allows osteo-competent cells to grow in the scaffold and generate a new tissue, eventually leading to the integration, regeneration, and healing of bone tissue . Mesenchymal stem cells (MSCs) are cells with fibroblast-like phenotypes capable of self-renewing and differentiating toward various mesenchymal lineages such as fat, bone, tendon, muscle, and cartilage cells due to both their trophic and regenerative properties. , …”