Cartilage Repair and Subchondral Bone Remodeling in Response to Focal Lesions in a Mini-Pig Model: Implications for Tissue Engineering

Abstract

The bony remodeling observed in this model system appears to be a biological phenomena and not a result of altered mechanical loading, with the depth of the focal chondral defect (partial vs. full thickness) dictating the bony remodeling response. The type of cartilage injury should be carefully controlled in studies utilizing this model to evaluate TE approaches for cartilage repair.

Fibrous Scaffolds with Varied Fiber Chemistry and Growth Factor Delivery Promote Repair in a Porcine Cartilage Defect Model

“…For instance, cartilage defects tend to heal spontaneously with rabbits, and it is difficult to create purely chondral defects with rodents due to the extremely thin cartilage layer. 43,44 Large animal models are more appropriate for translation of cartilage treatment strategies toward use with humans 27,43,44 ; for example, the porcine joint size and gait characteristics more accurately represent humans compared to smaller animals. 44 However, the cost, housing needs, and other factors associated with these larger animals (e.g., equine models) can be prohibitive for preliminary studies.…”

“…In total, 16 juvenile (i.e., 6 months old), castrated male Yucatan minipigs (Sinclair Bioresources) were utilized. Surgical protocols were as defined in Fisher et al 27 and involved bilateral surgeries, in which four defects were created in the trochlear groove of both hind limbs. Chondral defects were created using a 4-mm biopsy punch to outline the defect, followed by a curved blunt probe to remove cartilage from the defect area.…”

“…Indentation was applied at 0.1%/s strain ramp for 50 s. Resulting data were then fit using a Hertz model to obtain the Young's modulus (n = 7-10). 34,35 After mechanical testing, samples were fixed in 4% paraformaldehyde and imaged by microcomputed tomography (microCT; Scanco Viva CT75), with and without an iodine-based contrast solution (Lugol solution; Sigma), as in Fisher et al 27 Finally, samples were decalcified, processed for histology, and stained using Safranin-O/Fast Green, H&E, and immunohistochemistry for type 2 collagen (n = 7-10). Four blinded independent observers scored the resulting histology, using a modified version of the ICRS-II scoring system, 36 and images were quantified for percent stained area and staining intensity, as described in the following section.…”

“…Both systems were fabricated using a dual jet electrospinning system to produce multipolymer scaffolds, where hydrolytically degradable HA fiber components encapsulated and released TGFb3 for several weeks to further stimulate cartilaginous matrix production. These materials were implanted for 12 weeks in cartilage defects treated with microfracture using our established large animal (Yucatan minipig) model of cartilage repair, 27 and a comprehensive set of repair outcomes were analyzed, including gross appearance, defect fill, regenerate tissue mechanics, subchondral bone remodeling, and quantitative histological scoring, to determine the material combinations that best supported cartilage repair. This study provides a thorough investigation of the influence of various scaffold properties and growth factor release in an in vivo setting toward improved engineered scaffolds for cartilage repair applications.…”

Reparo de lesões induzidas na articulação femorotibiopatelar de ovinos através do implante de biomateriais associados à células-tronco de polpa dentária humana

“…Modelos pré-clínicos de reparação da cartilagem articular são importantes para abordagens experimentais (CARNEIRO; BARBIERI; FISHER et al, 2015) e devem ser escolhidos baseados na semelhança com a estrutura humana, com relação à anatomia, biologia celular e mecanismo articular (FISHER et al, 2015). Além disso, os modelos animais podem ser submetidos a procedimentos operatórios, que simulam e avaliam a viabilidade do procedimento, consequências fisiopatológicas e a eficácia terapêutica (FAGUNDES; TAHA, 2004).…”