Assessment of bone repair in animal models with suppressed osteoclast function by pretreatment of bisphosphonates

Bone lesions are an important public health problem, with high socioeconomic costs. Bone tissue repair is coordinated by an inflammatory dynamic process mediated by osteoprogenitor cells of the periosteum and endosteum, responsible for the formation of a new bone matrix. Studies using antioxidant products from plants for bone lesion treatment have been growing worldwide. We developed a systematic review to compile the results of works with animal models investigating the anti-inflammatory activity of plant extracts in the treatment of bone lesions and analyze the methodological quality of the studies on this subject. Studies were selected in the PubMed/MEDLINE, Scopus, and Web of Science databases according to the PRISMA statement. The research filters were constructed using three parameters: animal model, bone repair, and plant extracts. 31 full-text articles were recovered from 10 countries. Phytochemical prospecting was reported in 15 studies (48.39%). The most common secondary metabolites were flavonoids, cited in 32.26% studies (n=10). Essential criteria to in vivo animal studies were frequently underreported, suggesting publication bias. The animals treated with plant extracts presented positive results in the osteoblastic proliferation, and consequently, this treatment accelerated osteogenic differentiation and bone callus formation, as well as bone fracture repair. Possibly, these results are associated with antioxidant, regenerative, and anti-inflammatory power of the extracts. The absence or incomplete characterization of the animal models, treatment protocols, and phytochemical and toxicity analyses impairs the internal validity of the evidence, making it difficult to determine the effectiveness and safety of plant-derived products in bone repair.

Download Full-text

A tissue engineering approach to bone repair in large animal models and in clinical practice

Biomaterials ◽

10.1016/j.biomaterials.2007.06.023 ◽

2007 ◽

Vol 28 (29) ◽

pp. 4240-4250 ◽

Cited By ~ 362

Author(s):

Ranieri Cancedda ◽

Paolo Giannoni ◽

Maddalena Mastrogiacomo

Keyword(s):

Tissue Engineering ◽

Clinical Practice ◽

Animal Models ◽

Bone Repair ◽

Large Animal ◽

Engineering Approach ◽

Large Animal Models ◽

Tissue Engineering Approach

Download Full-text

Application of AMOR in Craniofacial Rabbit Bone Bioengineering

BioMed Research International ◽

10.1155/2015/628769 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Marcelo Freire ◽

Jeong-Ho Choi ◽

Anthony Nguyen ◽

Young Deok Chee ◽

Joong-Ki Kook ◽

...

Keyword(s):

Animal Models ◽

Bone Regeneration ◽

Bone Repair ◽

De Novo ◽

Absorbable Collagen Sponge ◽

Tissue Repair And Regeneration ◽

Novel Strategy ◽

Rat Calvarial Defect ◽

Ultimate Objective

Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable ofin vivocapturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks,de novobone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significantin vivobone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans, preclinical studies will be necessary to demonstrate the feasibility of AMOR in progressively larger animal models.

Download Full-text

Stem cell therapy for bone repair: a systematic review and meta-analysis of preclinical studies with large animal models

British Journal of Clinical Pharmacology ◽

10.1111/bcp.12382 ◽

2014 ◽

Vol 78 (4) ◽

pp. 718-726 ◽

Cited By ~ 23

Author(s):

Yun Liao ◽

Xiao-Long Zhang ◽

Ling Li ◽

Fu-Ming Shen ◽

Ming-Kang Zhong

Keyword(s):

Systematic Review ◽

Stem Cell ◽

Animal Models ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Bone Repair ◽

Meta Analysis ◽

Large Animal ◽

Preclinical Studies ◽

Large Animal Models

Download Full-text

Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.626315 ◽

2021 ◽

Vol 9 ◽

Author(s):

Piers Wilkinson ◽

Ilya Y. Bozo ◽

Thomas Braxton ◽

Peter Just ◽

Elena Jones ◽

...

Keyword(s):

Gene Therapy ◽

Animal Models ◽

Bone Repair ◽

Safety Data ◽

Clinical Translation ◽

Model Systems ◽

Large Animal ◽

Repair Gene ◽

Public Health Burden ◽

Large Animal Models

Bone defects and improper healing of fractures are an increasing public health burden, and there is an unmet clinical need in their successful repair. Gene therapy has been proposed as a possible approach to improve or augment bone healing with the potential to provide true functional regeneration. While large numbers of studies have been performed in vitro or in vivo in small animal models that support the use of gene therapy for bone repair, these systems do not recapitulate several key features of a critical or complex fracture environment. Larger animal models are therefore a key step on the path to clinical translation of the technology. Herein, the current state of orthopedic gene therapy research in preclinical large animal models was investigated based on performed large animal studies. A summary and an outlook regarding current clinical studies in this sector are provided. It was found that the results found in the current research literature were generally positive but highly methodologically inconsistent, rendering a comparison difficult. Additionally, factors vital for translation have not been thoroughly addressed in these model systems, and the risk of bias was high in all reviewed publications. These limitations directly impact clinical translation of gene therapeutic approaches due to lack of comparability, inability to demonstrate non-inferiority or equivalence compared with current clinical standards, and lack of safety data. This review therefore aims to provide a current overview of ongoing preclinical and clinical work, potential bottlenecks in preclinical studies and for translation, and recommendations to overcome these to enable future deployment of this promising technology to the clinical setting.

Download Full-text