Tuning adhesion failure strength for tissue-specific applications

Abstract

Soft tissue adhesives are employed to repair and seal many different organs, which range in both tissue surface chemistry and mechanical challenges during organ function. This complexity motivates the development of tunable adhesive materials with high resistance to uniaxial or multiaxial loads dictated by a specific organ environment. Co-polymeric hydrogels comprising aminated star polyethylene glycol and dextran aldehyde (PEG:dextran) are materials exhibiting physico-chemical properties that can be modified to achieve this organ- and tissue-specific adhesion performance. Here we report that resistance to failure under specific loading conditions, as well as tissue response at the adhesive material-tissue interface, can be modulated through regulation of the number and density of adhesive aldehyde groups. We find that atomic force microscopy (AFM) can characterize the material aldehyde density available for tissue interaction, and in this way enable rapid, informed material choice. Further, the correlation between AFM quantification of nanoscale unbinding forces with macroscale measurements of adhesion strength by uniaxial tension or multiaxial burst pressure allows the design of materials with specific cohesion and adhesion strengths. However, failure strength alone does not predict optimal in vivo reactivity. Thus, we demonstrate that the development of adhesive materials is significantly enabled when experiments are integrated along length scales to consider organ chemistry and mechanical loading states concurrently with adhesive material properties and tissue response.

Figure 1

(a) Schematic of AFM cantilevered probes functionalized with amine groups used to measure the rupture force between free amines and adhesive formulations, (b) rupture force for variation in the relative number of free aldehyde groups (compositions A-C; D10-50-8.75, D10-50-14, D10-50-18 with P8-10-25) or aldehyde group density (composition D; D10-20-23 P8-10-25), (c) degradation kinetics of different adhesive formulations listed above. Values reported as average ± standard error.

Figure 2

(a) Image and (b) schematic of tissue-material-tissue interface in uniaxial tensile loading, (c) adhesion strength of compositions A-D applied to a rat small intestine. Values reported as average ± standard deviation.

Figure 3

(a) Image and (b) schematic of burst pressure experiment; stresses within and at the interface are multiaxial, including interfacial shear as well as radial, longitudinal and hoop stresses σ_r, σ_land σ_h,(c) burst pressure of compositions A-D applied to a rat small intestine. Values reported as average ± standard deviation.

Figure 4

Morphology of the interfacial region between the two material formulations and excised rat small intestinal tissues using quantitative fluorescence microscopy. (a) composition A with 50% oxidation, D10-50-8.75 P8-10-25 (relative intensity 19.3±2.3) (b) composition D with 20% oxidation, D10-20-23 P8-10-25 (relative intensity 14.1±1.2). Three distinct regions are shown, T- tissue, I-interfacial region between the tissue and the adhesive material and B-bulk adhesive material.

Figure 5

Hematoxylin and Eosin staining of rabbit small intestinal tissue after 15 days of adhesive application with (a) composition A; D10-50-8.75 P8-10-25 (b) composition B; D10-50-14 P8-10-25. Scale bar is 1 mm. (c) magnification of the dashed area seen in figure 5b. scale bar is 200μm.