Extracellular matrix-based biomaterial scaffolds and the host response

Abstract

Extracellular matrix (ECM) proteins collectively represent a class of naturally derived proteinaceous biomaterials purified from harvested organs and tissues with increasing scientific focus and utility in tissue engineering and repair. This interest stems predominantly from the largely unproven concept that processed ECM biomaterials as natural tissue-derived matrices better integrate with host tissue than purely synthetic biomaterials. Nearly every tissue type has been decellularized and processed for re-use as tissue-derived ECM protein implants and scaffolds. To date, however, little consensus exists for defining ECM compositions or sources that best constitute decellularized biomaterials that might better heal, integrate with host tissues and avoid the foreign body response (FBR). Metrics used to assess ECM performance in biomaterial implants are arbitrary and contextually specific by convention. Few comparisons for in vivo host responses to ECM implants from different sources are published. This review discusses current ECM-derived biomaterials characterization methods including relationships between ECM material compositions from different sources, properties and host tissue response as implants. Relevant preclinical in vivo models are compared along with their associated advantages and limitations, and the current state of various metrics used to define material integration and biocompatibility are discussed. Commonly applied applications of these ECM-derived biomaterials as stand-alone implanted matrices and devices are compared with respect to host tissue responses.

Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult

“…In line with this, cardiac acellular scaffolds are an advantageous basis for the development of a bioartificial myocardium. However, when considering the clinical use of decellularized matrices several concerns have been raised namely batch-to-batch variability and stimulation of host immune response as a consequence of incomplete decellularization procedures [12][13][14]. Regardless, acellular scaffolds provide important insights on instructive ECM architecture and composition, which can be integrated in the development of biomimetic materials with controlled manufacturing and safety.…”

Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume

“…ECM can be derived from a variety of tissue sources (e.g. urinary bladder, skin, CNS) [3] and has found translation into a clinical setting to repair urinary bladder, muscle, peripheral nerve and heart, as well as being used in breast reconstruction [4-8]. …”

“…In contrast, synthetic scaffolds, such as polyethylene glyocol (PEG) hydrogels, typically require functionalization to achieve similar repair properties [10, 11]. Implantation of ECM typically induces a constructive structural remodeling of the bioscaffold mediated by the invasion of cells, notably macrophages, and subsequent deposition of site appropriate tissue [3]. Through degradation of the ECM bioscaffold and the release of signaling molecules, macrophages can be activated toward a repair phenotype promoting a gradual host tissue cell invasion, including stem/progenitor cells [12].…”

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

“…However, these efforts have been confounded by the host reaction after implantation. Most implanted biomaterials trigger an initial inflammatory response due to the host tissue reaction [5]. Inflammation is the body’s response to injury or foreign materials, and is present in numerous diseases, such as rheumatoid arthritis, infection, and cancer [6–8].…”