“Tissue Papers” from Organ‐Specific Decellularized Extracellular Matrices

Abstract

Using an innovative, tissue-independent approach to decellularized tissue processing and biomaterial fabrication, the development of a series of “tissue papers” derived from native porcine tissues/organs (heart, kidney, liver, muscle), native bovine tissue/organ (ovary and uterus), and purified bovine Achilles tendon collagen as a control from decellularized extracellular matrix particle ink suspensions cast into molds is described. Each tissue paper type has distinct microstructural characteristics as well as physical and mechanical properties, is capable of absorbing up to 300% of its own weight in liquid, and remains mechanically robust (E = 1–18 MPa) when hydrated; permitting it to be cut, rolled, folded, and sutured, as needed. In vitro characterization with human mesenchymal stem cells reveals that all tissue paper types support cell adhesion, viability, and proliferation over four weeks. Ovarian tissue papers support mouse ovarian follicle adhesion, viability, and health in vitro, as well as support, and maintain the viability and hormonal function of nonhuman primate and human follicle-containing, live ovarian cortical tissues ex vivo for eight weeks postmortem. “Tissue papers” can be further augmented with additional synthetic and natural biomaterials, as well as integrated with recently developed, advanced 3D-printable biomaterials, providing a versatile platform for future multi-biomaterial construct manufacturing.

Decellularized Extracellular Matrix Materials for Cardiac Repair and Regeneration

“…Grover et al used PEG‐acrylate materials to modulate mechanical properties of cECM scaffolds, and showed that fibroblast viability was not hindered by polymer inclusion . Jakus et al used a variety of dECM materials, including cECM, to create thin, large “tissue papers” for use in patching applications via the incorporation of poly‐lactic‐ co ‐glycolic acid (PLGA) . The cECM‐derived paper showed effective MSC proliferation, although the technology was not evaluated further in the study.…”

Bioengineering anin situovary (ISO) for fertility preservation

“…Recently, bovine ovaries have been decellularized using detergent-based methods to obtain a tissue-specific scaffold, which was re-seeded with healthy follicles and transplanted to restore cycling in an ovariectomized mouse 67 . Similarly, porcine and bovine decellularized ovaries were further processed into "tissue papers", demonstrating a versatile approach for short-term in vitro culture of nonhuman primate and human ovarian cortical strips 68 . Although acellular ovarian scaffolds have been shown to support follicle function in this form, they are limited by the quantity of follicles that can be seeded and require additional time for in vitro culture to allow follicles to attach.…”

Comparative Evaluation of the Book‐Type Acellular Bone Scaffold and Fibrocartilage Scaffold for Bone‐Tendon Healing

“…Additionally, this scaffold has diverse physiological functions such as being a reservoir of cytokines and GFs, transmitting specific signals through interactions with the receptors of the cell surface, and providing natural circumstances to regulate the phenotype, attachment, migration and proliferation of cells . Recently, several kinds of acellular scaffolds have been successfully developed for tissue‐engineering . Unfortunately, the acellular scaffolds derived from dense tissue is low in porosity, and thus not convenient for cell infiltration, partly limiting their usage .…”