A biomechanical test model for evaluating osseous and osteochondral tissue adhesives

Abstract

Background: Currently there are no standard models with which to evaluate the biomechanical performance of calcified tissue adhesives, in vivo. We present, herein, a pre-clinical murine distal femoral bone model for evaluating tissue adhesives intended for use in both osseous and osteochondral tissue reconstruction. Results: Cylindrical cores (diameter (Ø) 2 mm (mm) × 2 mm depth), containing both cancellous and cortical bone, were fractured out from the distal femur and then reattached using one of two tissue adhesives. The adhesiveness of fibrin glue (Tisseel tm ), and a novel, biocompatible, calcium phosphate-based tissue adhesive (OsStic tm ) were evaluated by pullout testing, in which glued cores were extracted and the peak force at failure recorded. The results show that Tisseel weakly bonded the metaphyseal bone cores, while OsStic produced > 30-fold higher mean peak forces at failure (7.64 Newtons (N) vs. 0.21 N). The failure modes were consistently disparate, with Tisseel failing gradually, while OsStic failed abruptly, as would be expected with a calcium-based material. Imaging of the bone/ adhesive interface with microcomputed tomography revealed that, for OsStic, failure occurred more often within cancellous bone (75% of tested samples) rather than at the adhesive interface.Conclusions: Despite the challenges associated with biomechanical testing in small rodent models the preclinical ex-vivo test model presented herein is both sensitive and accurate. It enabled differences in tissue adhesive strength to be quantified even for very small osseous fragments (<Ø4mm). Importantly, this model can easily be scaled to larger animals and adapted to fracture fragment fixation in human bone. The present model is also compatible with other long-term in vivo evaluation methods (i.e. in vivo imaging, histological analysis, etc.).

Phosphoserine Functionalized Cements Preserve Metastable Phases, and Reprecipitate Octacalcium Phosphate, Hydroxyapatite, Dicalcium Phosphate, and Amorphous Calcium Phosphate, during Degradation, In Vitro

“…Most importantly, PMCs display a completely novel property for cements: strong adhesion to biomaterial and tissue surfaces [60,61]. As an adhesive, PMCs can effectively adhere to, and reconstruct, calcified [62] and soft tissue injuries [63], ex vivo. However, before testing PMCs in vivo, the degradation and dissolution properties must be investigated in vitro, and ex vivo.…”

Factors That Determine the Adhesive Strength in a Bioinspired Bone Tissue Adhesive

“…Tukey or Games-Howell post-hoc analysis was used when variance was homogeneous, or inhomogeneous (Levene's test), respectively. Single comparisons were made with "group" as the independent variable, and "shear strength" as the dependent continuous variable for the following intergroup comparisons: (groups #1-6), (groups #3, 6-12, 33-34), (groups #3, [13][14][15][16][17][18][19][20][21], and (groups #24-32). A comparison of means (ANOVA) was also made between independent variable "group", and dependent variable "failure mode".…”

“…The following covariates (uncontrolled factors) were recorded for each sample: application time, average bond thickness, the thickest bond, or thinnest bond thickness, bond unevenness (difference between the thickest and thinnest bond, normalized to the average bond thickness for the sample), and the failure mode ( Table 1). The correlation strength between each individual factor and the outcome measure (adhesive strength), was explored in scatter plots, with replications of a single formulation of PMC ( Figure 6A-D, n = 242 total, n = 12 or 36 per group, 27% PMC, groups #1-13), or a series of PMC formulations with differing amounts of phosphoserine ( Figure 6E-H, n = 12 or 36 per group, 27-90% PMC, groups #3, [14][15][16][17][18][19][20][21].…”

“…No trend was obvious in the sample mean distribution using categorical scatter plots for: cure type, grip force, grip time, or mixing method (data not shown). A second set of scatter plots (aggregated) evaluated the relationship between different strength PMC formulations ( Figure 6E-H, n = 12 or 36 per group, 27%-90% PMC, groups #3, [13][14][15][16][17][18][19][20][21], and: application time ( Figure 6E), average bond thickness ( Figure 6F), the thinnest (red) and thickest bond ( Figure 6G), and bond unevenness ( Figure 6H). A number of studies have investigated the relationship between bond thickness and adhesive strength, with some reporting similar results (poor correlation) [33,34,40], a positive correlation [23,41], or a negative correlation [21,42].…”

“…Three covariates were excluded from the linear regression model, "application time", "thickest bond thickness" and "thinnest bond thickness", because they were collinear with other factors. The second regression model was built using different formulations (phosphoserine mole %) of PMC (Table 4, n = 142 total, n = 12 or 36 per group, 27%-90% PMC, groups #3, [13][14][15][16][17][18][19][20][21]. A stepwise linear regression model revealed that: (a) the correlation between shear strength and the fixed factors "cure condition", "grip duration", and "formulation" was weak (R 2 = 0.216); (b) inclusion of the following covariates, stepwise in separate "blocks", improved the correlation model: average bond thickness (R 2 = 0.237), unevenness (R 2 = 0.243), and the failure mode (R 2 = 0.377).…”