Myocardial matrix–polyethylene glycol hybrid hydrogels for tissue engineering

Abstract

Similar to other protein-based hydrogels, extracellular matrix (ECM) based hydrogels, derived from decellularized tissues, have a narrow range of mechanical properties and are rapidly degraded. These hydrogels contain natural cellular adhesion sites, form nanofibrous networks similar to native ECM, and are biodegradable. In this study, we expand the properties of these types of materials by incorporating poly(ethylene glycol) (PEG) into the ECM network. We use decellularized myocardial matrix as an example of a tissue specific ECM derived hydrogel. Myocardial matrix-PEG hybrids were synthesized by two different methods, cross-linking the proteins with an amine-reactive PEG-star and photo-induced radical polymerization of two different multi-armed PEG-acrylates. We show that both methods allow for conjugation of PEG to the myocardial matrix by gel electrophoresis and infrared spectroscopy. Scanning electron microscopy demonstrated that the hybrid materials still contain a nanofibrous network similar to unmodified myocardial matrix and that the fiber diameter is changed by the method of PEG incorporation and PEG molecular weight. PEG conjugation also decreased the rate of enzymatic degradation in vitro, and increased material stiffness. Hybrids synthesized with amine-reactive PEG had gelation rates of thirty minutes, similar to the unmodified myocardial matrix, and incorporation of PEG did not prevent cell adhesion and migration through the hydrogels, thus offering the possibility to have an injectable ECM hydrogel that degrades more slowly in vivo. The photo-polymerized radical systems gelled in four minutes upon irradiation allowing for 3D encapsulation and culture of cells, unlike the soft unmodified myocardial matrix. This work demonstrates PEG incorporation into ECM-based hydrogels can expand material properties, thereby opening up new possibilities for in vitro and in vivo applications.

Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction

“…[12,38,39] To achieve long-term mechanical stability, the use of injectable ECM, as with other natural based gels, requires mechanical reinforcement-critical for the proper remodeling of the damaged LV tissue. The natural gel, comprising pcECM alone, was very soft and unstable and thus, was not durable enough when cultured with cells ( Figure 1E), which is similar to the findings of Grover et al [19]. These weak mechanical properties might also fail to provide the longstanding support required by the heart, possibly leading to the breakdown of the gel during heart contraction and relaxation.…”

“…[8,16,19,37] ECM's dynamic reciprocal communication with the tissue's cellular component plays a fundamental role in tissue development, signaling and function. [38,39] Though ECM components in different tissues may be similar, each tissue holds a unique combination and 3D structure of macromolecules that provide the cells with the required cues and mechanical support.…”

Collagen matrix as a tool in studying fibroblastic cell behavior

“…PEG gels retain fibrillar structure, are more resistant to enzymatic degradation and do not inhibit metabolic activity of incorporated fibroblasts. 41 …”

Quantification of DNA in urinary porcine bladder matrix using the ACTB gene

“…In this work, we used two protocols for UBM decellularization that employ the detergents most commonly used: SDS (Mirsadraee et al 2006;Bolland et al 2007;Ott et al 2008;Rosario et al 2008;Singelyn et al 2009;DeQuach et al 2010;Liu et al 2011;Choi et al 2012;Grover et al 2014), which is generally thought to be harsher to the tissue with greater disruption of protein structure and loss of matrix components (Gilbert 2012); and Triton X-100 (Brown et al 2006(Brown et al , 2010Chun et al 2007;Ott et al 2008;Singelyn et al 2009), which is theoretically the most desirable detergent because it should minimally impact protein and connective tissue structure due to its lack of ionic charge (Gilbert 2012). This idea was supported by the Masson staining (Fig.…”