A preclinical large-animal model for the assessment of critical-size load-bearing bone defect reconstruction

Sparks, David S.; Saifzadeh, Siamak; Savi, Flávia Medeiros; Dlaska, Constantin Edmond; Berner, Arne; Henkel, Janin; Reichert, Johannes C.; Wullschleger, Martin; Ren, Jiongyu; Cipitria, Amaia; McGovern, Jacqui A.; Steck, Roland; Wagels, Michael; Woodruff, Maria A.; Schuetz, Michael; Hutmacher, Dietmar W.

doi:10.1038/s41596-019-0271-2

Cited by 94 publications

(106 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specific aspects related to the selection of animal species, on the other hand, include anatomical and/or skeletal similarity, osseous macro-and microstructure, bone turnover and weight/loading patterns. In this sense, skeletally mature animals of large size and weight (e.g., pigs, dogs, sheep or goats) generally mimic the human physiological condition better than small animals [90,92,98]. Nonetheless, the use of small animals (i.e., rats or rabbits) is acceptable for the preliminary biomechanical assessment and initial validation of load-bearing models but should be followed by more clinically relevant animal models [92,99].…”

Section: Selection Of the Animal Speciesmentioning

confidence: 99%

“…In this sense, skeletally mature animals of large size and weight (e.g., pigs, dogs, sheep or goats) generally mimic the human physiological condition better than small animals [90,92,98]. Nonetheless, the use of small animals (i.e., rats or rabbits) is acceptable for the preliminary biomechanical assessment and initial validation of load-bearing models but should be followed by more clinically relevant animal models [92,99]. Detailed comparisons between pig, dog, sheep and goat models have been extensively described in the literature [92,94,98,100].…”

Section: Selection Of the Animal Speciesmentioning

confidence: 99%

“…Nonetheless, the use of small animals (i.e., rats or rabbits) is acceptable for the preliminary biomechanical assessment and initial validation of load-bearing models but should be followed by more clinically relevant animal models [92,99]. Detailed comparisons between pig, dog, sheep and goat models have been extensively described in the literature [92,94,98,100].…”

Section: Selection Of the Animal Speciesmentioning

confidence: 99%

“…Together, these techniques can provide a comprehensive assessment of the regenerated bone and its effectiveness in mitigating bone loss [100]. Nonetheless, the functional capability and structural integrity of both the newly formed and surrounding bone cannot be assessed solely through the previously mentioned techniques [144], for which ex-vivo mechanical testing of the freshly explanted bone samples is essential and arguably the most important outcome measurement [92,98].…”

Section: Outcome Measurementsmentioning

confidence: 99%

“…A wide variety of animals has been used during the past decades for the preclinical evaluation of highly loaded bone defects, ranging from small animals such as mice, rats and rabbits, to large animals, namely sheep, dogs, pigs and cows [ 89 , 90 , 91 ]. In general, we argue that the selection of an animal model for preclinically evaluating BSMs should follow the key principles explained in the sections below [ 7 , 92 , 93 ] ( Figure 2 ): 1. Selection of the animal species: the selected animal species should resemble the human physiological and pathophysiological response as closely as possible; 2.…”

Section: Animal Models For Critical Load-bearing Bone Defectsmentioning

confidence: 99%

See 4 more Smart Citations

Pre-Clinical Evaluation of Biological Bone Substitute Materials for Application in Highly Loaded Skeletal Sites

2020

View full text Add to dashboard Cite

The development of bone substitute materials (BSMs) intended for load-bearing bone defects is highly complicated, as biological and mechanical requirements are often contradictory. In recent years, biological BSMs have been developed which allow for a more efficient integration of the material with the surrounding osseous environment and, hence, a higher mechanical stability of the treated defect. However, while these materials are promising, they are still far from ideal. Consequently, extensive preclinical experimentation is still required. The current review provides a comprehensive overview of biomechanical considerations relevant for the design of biological BSMs. Further, the preclinical evaluation of biological BSMs intended for application in highly loaded skeletal sites is discussed. The selected animal models and implantation site should mimic the pathophysiology and biomechanical loading patterns of human bone as closely as possible. In general, sheep are among the most frequently selected animal models for the evaluation of biomaterials intended for highly loaded skeletal sites. Regarding the anatomical sites, segmental bone defects created in the limbs and spinal column are suggested as the most suitable. Furthermore, the outcome measurements used to assess biological BSMs for regeneration of defects in heavily loaded bone should be relevant and straightforward. The quantitative evaluation of bone defect healing through ex vivo biomechanical tests is a valuable addition to conventional in vivo tests, as it determines the functional efficacy of BSM-induced bone healing. Finally, we conclude that further standardization of preclinical studies is essential for reliable evaluation of biological BSMs in highly loaded skeletal sites.

show abstract

Section: Selection Of the Animal Speciesmentioning

confidence: 99%

Section: Selection Of the Animal Speciesmentioning

confidence: 99%

Section: Selection Of the Animal Speciesmentioning

confidence: 99%

Section: Outcome Measurementsmentioning

confidence: 99%

Section: Animal Models For Critical Load-bearing Bone Defectsmentioning

confidence: 99%

See 3 more Smart Citations

Pre-Clinical Evaluation of Biological Bone Substitute Materials for Application in Highly Loaded Skeletal Sites

2020

View full text Add to dashboard Cite

show abstract

Highly Malleable Personalized Prostheses with Hierarchical Microstructure Boost the Long‐Term Osteointegration in Irregular Craniofacial Reconstruction

Liu,

Tong,

Chen

et al. 2023

Adv Funct Materials

View full text Add to dashboard Cite

The desired clinical bone prostheses should achieve satisfactory interface integration and osteoinduction, as well as good surgical convenience. Here, a highly malleable 3D printed prosthesis with compressive strength at 13 MPa is constructed by dopamine, polyvinyl alcohol, and micro‐sized hydroxyapatite (86 wt%) as composite bioinks, which is endowed with good plasticity and can quickly match irregular defects by easily trimming. Spatially decorated collagen and hyaluronan greatly enriched the hierarchical microstructure and biological activity of malleable prosthesis. This prosthesis accelerates the proliferation and osteogenic differentiation of stem cells, regulates M2 polarization of macrophage, and promotes endogenous stem cell recruitment and early angiogenesis. Meanwhile, it significantly reinforces biomineralized deposition and vascularization, reaches full coverage of new bone in the rabbit cranial defect after 15 weeks (Φ = 10 mm), and achieves well osseointegration capacity with interfacial binding strength at 71.2% of the natural skull. This osteoinductive prosthesis provides a new design idea for bone filling.

show abstract

Regeneration of Critical‐Sized Mandibular Defects Using 3D‐Printed Composite Scaffolds: A Quantitative Evaluation of New Bone Formation in In Vivo Studies

Dalfino

Savadori

Piazzoni

et al. 2023

Adv Healthcare Materials

View full text Add to dashboard Cite

Mandibular tissue engineering aims to develop synthetic substitutes for the regeneration of critical size defects (CSD) caused by a variety of events, including tumor surgery and post‐traumatic resections. Currently, the gold standard clinical treatment of mandibular resections (i.e., autologous fibular flap) has many drawbacks, driving research efforts toward scaffold design and fabrication by additive manufacturing (AM) techniques. Once implanted, the scaffold acts as a support for native tissue and facilitates processes that contribute to its regeneration, such as cells infiltration, matrix deposition and angiogenesis. However, to fulfil these functions, scaffolds must provide bioactivity by mimicking natural properties of the mandible in terms of structure, composition and mechanical behavior. This review aims to present the state of the art of scaffolds made with AM techniques that are specifically employed in mandibular tissue engineering applications. Biomaterials chemical composition and scaffold structural properties are deeply discussed, along with strategies to promote osteogenesis (i.e., delivery of biomolecules, incorporation of stem cells, and approaches to induce vascularization in the constructs). Finally, a comparison of in vivo studies is made by taking into consideration the amount of new bone formation (NB), the CSD dimensions, and the animal model.

show abstract

A preclinical large-animal model for the assessment of critical-size load-bearing bone defect reconstruction

Cited by 94 publications

References 110 publications

Pre-Clinical Evaluation of Biological Bone Substitute Materials for Application in Highly Loaded Skeletal Sites

Pre-Clinical Evaluation of Biological Bone Substitute Materials for Application in Highly Loaded Skeletal Sites

Highly Malleable Personalized Prostheses with Hierarchical Microstructure Boost the Long‐Term Osteointegration in Irregular Craniofacial Reconstruction

Regeneration of Critical‐Sized Mandibular Defects Using 3D‐Printed Composite Scaffolds: A Quantitative Evaluation of New Bone Formation in In Vivo Studies

Contact Info

Product

Resources

About