Advances in biomimetic regeneration of elastic matrix structures

Abstract

Elastin is a vital component of the extracellular matrix, providing soft connective tissues with the property of elastic recoil following deformation and regulating the cellular response via biomechanical transduction to maintain tissue homeostasis. The limited ability of most adult cells to synthesize elastin precursors and assemble them into mature crosslinked structures has hindered the development of functional tissue-engineered constructs that exhibit the structure and biomechanics of normal native elastic tissues in the body. In diseased tissues, the chronic overexpression of proteolytic enzymes can cause significant matrix degradation, to further limit the accumulation and quality (e.g., fiber formation) of newly deposited elastic matrix. This review provides an overview of the role and importance of elastin and elastic matrix in soft tissues, the challenges to elastic matrix generation in vitro and to regenerative elastic matrix repair in vivo, current biomolecular strategies to enhance elastin deposition and matrix assembly, and the need to concurrently inhibit proteolytic matrix disruption for improving the quantity and quality of elastogenesis. The review further presents biomaterial-based options using scaffolds and nanocarriers for spatio-temporal control over the presentation and release of these biomolecules, to enable biomimetic assembly of clinically relevant native elastic matrix-like superstructures. Finally, this review provides an overview of recent advances and prospects for the application of these strategies to regenerating tissue-type specific elastic matrix structures and superstructures.

Nanoparticle-based targeted delivery of pentagalloyl glucose reverses elastase-induced abdominal aortic aneurysm and restores aorta to the healthy state in mice

“…Unfortunately, adults cells cannot regenerate lost elastic fibers on their own as the microfibrillar assembly is lacking 23 . Furthermore, degraded elastic lamina can release elastin degradation products (EDPs) that are chemokines for inflammatory cells and modulate M1/M2 macrophage polarization 24 .…”

Nanoparticles for localized delivery of hyaluronan oligomers towards regenerative repair of elastic matrix

“…Collagen, which primarily imparts stiffness to soft tissues, is generated prolifically by cells (SMCs, fibroblasts) well into adulthood and in response to injury [25]. However, adult cells are inherently poor in their ability to synthesize elastin and crosslink it into a mature matrix, although this can be overcome by exogenous delivery of elastogenic biomolecules [26], Therefore, our long-term goal is to develop modalities for localized, controlled, and sustained delivery of HA-o to tissue sites of proteolytic disease such as within AAA tissues towards inducing biomimetic cellular regeneration of the elastic matrix, which poorly occurs naturally.…”

Nitric Oxide Stimulates Matrix Synthesis and Deposition by Adult Human Aortic Smooth Muscle Cells Within Three-Dimensional Cocultures

“…Despite recent progress in the field of vascular tissue engineering, elastin synthesis and deposition by vascular SMCs within 3D constructs remain a formidable challenge. 18,66 This is partially due to the highly reduced ability of adult SMCs, at both transcription and translation levels, to synthesize, release, and deposit mature elastin. Thus, the overarching goal of cellular or tissue engineering approaches is to stimulate these adult SMCs, using an optimal combination of biochemical and biomechanical cues, to deposit mature and crosslinked elastin within blood vessels.…”