Tailoring material properties of a nanofibrous extracellular matrix derived hydrogel

Abstract

In the native tissue, the interaction between cells and the extracellular matrix (ECM) is essential for cell migration, proliferation, differentiation, mechanical stability, and signaling. It has been shown that decellularized ECMs can be processed into injectable formulations, thereby allowing for minimally invasive delivery. Upon injection and increase in temperature, these materials self-assemble into porous gels forming a complex network of fibers with nano-scale structure. In this study we aimed to examine and tailor the material properties of a self-assembling ECM hydrogel derived from porcine myocardial tissue, which was developed as a tissue specific injectable scaffold for cardiac tissue engineering. The impact of gelation parameters on ECM hydrogels has not previously been explored. We examined how modulating pH, temperature, ionic strength, and concentration affected the nanoscale architecture, mechanical properties, and gelation kinetics. These material characteristics were assessed using scanning electron microscopy, rheometry, and spectrophotometry, respectively. Since the main component of the myocardial matrix is collagen, many similarities between the ECM hydrogel and collagen gels were observed in terms of the nanofibrous structure and modulation of properties by altering ionic strength. However, variation from collagen gels was noted for the gelation temperature along with varied times and rates of gelation. These discrepancies when compared to collagen are likely due to the presence of other ECM components in the decellularized ECM based hydrogel. These results demonstrate how the material properties of ECM hydrogels could be tailored for future in vitro and in vivo applications.

Fabrication and characterization of injectable hydrogels derived from decellularized skeletal and cardiac muscle

“…Although they can be tissue-specific regarding biochemical composition, decellularized hydrogels are typically weaker than the tissues from which they are derived [31, 32]. This can vary due to the harshness of the decellularization method [27].…”

“…Example traces for both muscle ECM hydrogels are shown in Figure 4A and B. Reported at 1 rad/s, values for storage modulus typically range between 5 and 10 Pa and loss modulus between 1 and 5 Pa [12, 31, 32]. Quantifying complex viscosity also shows the potential of the material for injectability and/or catheter delivery.…”

“…Porous nanofibrous architecture may be desirable to resemble the native ECM conditions, as the main ECM component, collagen, forms a nanofibrous architecture in vivo [33, 34]. Fiber diameters can also affect the mechanical properties and self assembly of the hydrogel; we have found that fibers with diameters between 30 – 250 nm and an average diameter of 100 nm form upon self-assembly of the muscle ECM hydrogels [31]. Figure 4E and F display example SEM images for the skeletal muscle and cardiac ECM hydrogels.…”

Injectable Shear-Thinning Hydrogels for Minimally Invasive Delivery to Infarcted Myocardium to Limit Left Ventricular Remodeling

“…14–16 While they have proceeded to clinical trials, the modest stiffness of these materials (10 Pa for decellularized ECM) 17 make them unsuitable for mechanical stabilization of the infarct. It has been demonstrated that supraphysiological hydrogel moduli of approximately 40 kPa effectively attenuate LV remodeling.…”

In Vitro Characteristics of Porcine Tendon Hydrogel for Tendon Regeneration

“…34 Logically, a number of hydrogels have been developed from the very tissues that they aim to treat in an attempt to provide the native cues for cell-matrix interactions and injury response. [35][36][37][38][39][40][41] These substances, solutions of various ECMs, have been shown to possess favorable cues for cellular infiltration, migration, and proliferation. A native tissue-derived microenvironment such as this could serve as the foundation on which healing may occur.…”