Decellularized musculofascial extracellular matrix for tissue engineering

Abstract

Ideal scaffolds that represent native extracellular matrix (ECM) properties of musculofascial tissues have great importance in musculofascial tissue engineering. However, detailed characterization of musculofascial tissues’ ECM (particularly, of fascia) from large animals is still lacking. In this study, we developed a decellularization protocol for processing pig composite musculofascial tissues. Decellularized muscle (D-muscle) and decellularized fascia (D-fascia), which are two important components of decellularized musculofascial extracellular matrix (DMM), were comprehensively characterized. D-muscle and D-fascia retained intact three-dimensional architecture, strong mechanical properties, and bioactivity of compositions such as collagen, laminin, glycosaminoglycan, and vascular endothelial growth factor. D-muscle and D-fascia provided a compatible niche for human adipose-derived stem cell integration and proliferation. Heterotopic and orthotopic implantation of D-muscle and D-fascia in a rodent model further proved their biocompatibility and myogenic properties during the remodeling process. The differing characteristics of D-muscle from D-fascia (e.g., D-muscle’s strong pro-angiogenic and pro-myogenic properties vs. D-fascia’s strong mechanical properties) indicate different clinical application opportunities of D-muscle vs. D-fascia scaffolds. DMM comprising muscle and fascia ECM as a whole unit can thus provide not only a clinically translatable platform for musculofascial tissue repair and regeneration but also a useful standard for scaffold design in musculofascial tissue engineering.

Chemical decellularization: a promising approach for preparation of extracellular matrix

“…Triton X-100 (octyl phenol ethoxylate) is the most frequently used non-ionic detergent in decellularized protocols and it is applied mostly for thin tissues such as heart valves, blood vessels and ligaments. The exposure time of tissues to Triton X-100 can vary among different protocols, ranging in time from 6 h to 14 days [26][27][28] . Different periods of exposure have different decellularization results.…”

“…In addition, agitation can also be used for rinsing residual detergents, by means of PBS washing cycles. It may be used for heart valves 28 , muscles 46 , peripheral nerves 47 , trachea 48 and dermis 49 .…”

Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization

“…Various techniques for decellularization and recellularization have been examined for pre-clinical interventions of miscellaneous tissues, e.g., small intestine [13,14], urinary bladder [15], heart valves [16], larynx [17], dermis [18], musculofascial tissue [19] and nerves [20,21]. Concerning the female internal genital tract, small patches of myometrial tissue were recently decellularized using a modified protocol that had been optimized for decellularization of blood vessels [22].…”

Biologic Scaffolds

“…Growth factors are bioactive molecules responsible for the activation of a plethora of cellular pathways that modulate cell survival, proliferation, and differentiation. The presence of vascular endothelial growth factor (VEGF) (Wang et al 2013b), fibroblast growth factor (FGF) family (Hoganson et al 2010), epidermal growth factor (EGF), transforming growth factor b (TGF-b), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF) (Soto-Gutierrez et al 2011;Ren et al 2013), platelet-derived growth factor (PDGF), and nerve growth factor (NGF), among others, within ECM bioscaffolds has been shown (Meezan et al 1975;Bissell et al 1982;Gilbert et al 2006;Badylak et al 2008a;Crapo et al 2012;Wolf et al 2012). …”