Translational relevance of the goat as a preclinical model of the human labrum and chondrolabral junction-histological study.

The purpose of this study was to evaluate the histologic features of the caprine labrum, with emphasis on the chondrolabral junction, with the goal of informing the feasibility of the goat as an animal model. The left hip joint of six adolescent Spanish goats (Capra pyrenaica) was harvested and subjected to anatomical and histological assessments. Human acetabular and femoral head samples, collected during total hip arthroplasty, served as comparison samples. The caprine labrum was found to consist of mostly type I collagen with uniform crimp, with an average crimp length of 20.8 µm. Upon histological assessment, acetabular articular chondrocytes were found to express substance-P, especially near or in the chondrolabral junction. And the majority of nonvascular cells expressed α-smooth muscle actin (SMA), with no notable elastin and laminin expression. Human labrum demonstrated similar staining patterns. Overall, the goat hip was found to be homologous to the human hip, demonstrating potential as a useful animal model for future studies. This is the first report of a crimped collagen structure in the labrum. Crimped type I collagen at the chondrolabral junction imparts an extension-recovery property which allows for toleration of stress without permanent deformation, underlying the importance of its preservation during surgery. The high expression of substance-P reflects the degree to which the labrum is innervated. Finally, the expression of α-SMA with contractile characteristics could indicate the potential for chondrocyte (i.e., myochondrocytes) modeling of the extracellular matrix. Statement of Clinical Significance: Establishment of a large animal model and deeper knowledge of the histological composition of the hip joint will enhance our study of the acetabular labrum, including repair techniques. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1070-1080, 2020.

Chemotactic recruitment of adult neural progenitor cells into multifunctional hydrogels providing sustained SDF-1α release and compatible structural support.

Without chemotactic cues and structural support, cavitary brain lesions typically fail to recruit endogenous neural progenitor cells (NPCs). Toward resolving this, we engineered multifunctional biomaterials comprising injectable gelatin-hydroxyphenylpropionic acid (Gtn-HPA) hydrogels and dextran sulfate/chitosan polyelectrolyte complex nanoparticles (PCNs) that delivered stromal cell-derived factor-1α (SDF-1α). Over 7 d of interface with in vitro tissue simulant containing adult rat hippocampal NPCs (aNPCs) and their neuronal progeny, Gtn-HPA/SDF-1α-PCN hydrogels promoted chemotactic recruitment to enhance infiltration of aNPCs by 3- to 45-fold relative to hydrogels that lacked SDF-1α or vehicles to sustain SDF-1α release. When cross-linked with 0.85-0.95 mM HO, Gtn-HPA/SDF-1α-PCN hydrogels provided optimally permissive structural support for migration of aNPCs. Specific matrix metalloproteinase (MMP) inhibitors revealed that 42, 30, and 55% of cell migration into Gtn-HPA/SDF-1α-PCN hydrogels involved MMP-2, 3, and 9, respectively, demonstrating the hydrogels to be compatible toward homing endogenous NPCs, given their expression of similar MMPs. Interestingly, PCNs utilized FGF-2 found in situ to induce chemokinesis, potentiate SDF-1α chemotactic recruitment, and increase proliferation of recruited cells, which collectively orchestrated a higher number of migrated aNPCs. Overall, Gtn-HPA/SDF-1α-PCN hydrogels prove to be promising biomaterials for injection into cavitary brain lesions to recruit endogenous NPCs and enhance neural tissue repair/regeneration.