Biologic scaffolds composed of central nervous system extracellular matrix

Abstract

Acellular biologic scaffolds are commonly used to facilitate the constructive remodeling of three of the four traditional tissue types: connective, epithelial, and muscle tissues. However, the application of extracellular matrix (ECM) scaffolds to neural tissue has been limited, particularly in the central nervous system (CNS) where intrinsic regenerative potential is low. The ability of decellularized liver, lung, muscle, and other tissues to support tissue-specific cell phenotype and function suggests that CNS-derived biologic scaffolds may help to overcome barriers to mammalian CNS repair. A method was developed to create CNS ECM scaffolds from porcine optic nerve, spinal cord, and brain, with decellularization verified against established criteria. CNS ECM scaffolds retained neurosupportive proteins and growth factors and, when tested with the PC12 cell line in vitro, were cytocompatible and stimulated proliferation, migration, and differentiation. Urinary bladder ECM (a non-CNS ECM scaffold) was also cytocompatible and stimulated PC12 proliferation but inhibited migration rather than acting as a chemoattractant over the same concentration range while inducing greater rates of PC12 differentiation compared to CNS ECM. These results suggest that CNS ECM may provide tissue-specific advantages in CNS regenerative medicine applications and that ECM scaffolds in general may aid functional recovery after CNS injury.

Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering

“…Removal of cells and antigens is essential to preventing an immune response; however, decellularization must also maintain the composition and structure of the native tissue [33][34][35][36]. Decellularization techniques have been optimized for the heart [37], lung [38], nerve [39], skin [40], brain [41], and spinal cord [42], among other tissues, and can involve physical, chemical, and biological methods to lyse cells, and subsequently remove cellular debris. Our laboratory has previously developed gentle decellularization techniques for nerve tissue to preserve essential proteins, proteoglycans, and microstructure [39,43], which would be ideal for the delicate nucleus pulposus.…”

Tissue-Specific Effects of Esophageal Extracellular Matrix

“…Similarly, ECM scaffolds have been isolated from tissues ranging from the urinary bladder and small intestine to the spinal cord and brain, [1][2][3] among others. Implantation and subsequent degradation of ECM scaffolds lead to the release or exposure of cryptic peptide fragments that affect cell behavior and tissue remodeling events.…”

“…2,[4][5][6][7][8][9][10][11] The homologous ECM can preferentially maintain tissuespecific cell phenotypes, [4][5][6][7] promote cell proliferation, 6,8 induce tissue-specific differentiation, 9 and enhance the chemotaxis of stem cells. 2,10,12 However, the preference or necessity for tissue-specific ECM has not been shown for all therapeutic applications. [13][14][15] The objective of the present study was to compare the cellular response to esophageal ECM (eECM) versus small intestinal submucosa (SIS)-ECM and urinary bladder matrix (UBM) in vitro and in vivo.…”

Implantation of Brain-derived Extracellular Matrix Enhances Neurological Recovery after Traumatic Brain Injury

“…16 Briefly, porcine brain tissue was obtained from animals (approximately 120 kg) at a local abattoir (Thoma's Meat Market, Saxonburg, PA). Tissues were frozen at À80 C for at least 16 h, thawed completely, and separated from all non-central nervous system (CNS) tissues.…”