Designing Biopolymer Microthreads for Tissue Engineering and Regenerative Medicine

Abstract

Native tissue structures possess elaborate extracellular matrix (ECM) architectures that inspire the design of fibrous structures in the field of regenerative medicine. We review the literature with respect to the successes and failures, as well as the future promise of biopolymer microthreads as scaffolds to promote endogenous and exogenous tissue regeneration. Biomimetic microthread tissue constructs have been proposed for the functional regeneration of tendon, ligament, skeletal muscle, and ventricular myocardial tissues. To date, biopolymer microthreads have demonstrated promising results as materials to recapitulate the hierarchical structure of simple and complex tissues and well as biochemical signaling cues to direct cell-mediated tissue regeneration. Biopolymer microthreads have also demonstrated exciting potential as a platform technology for the targeted delivery of stem cells and therapeutic molecules. Future studies will focus on the design of microthread-based tissue analogs that strategically integrate growth factors and progenitor cells to temporally direct cell-mediated processes that promote enhanced functional tissue regeneration.

Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss

“…Many strategies have been explored to create scaffolds with anisotropic surface topography, including patterned substrates [154][155][156][157][158][159][160][161]. electrospun fibers [122,123,155,[162][163][164][165], microthreads [166][167][168], and aligned pores [169][170][171]. A review describes these methods in detail and their ability to align and differentiate myoblasts in vitro, as this falls outside of the scope of this review [172].…”

Horseradish Peroxidase-Catalyzed Crosslinking of Fibrin Microthread Scaffolds

“…14,15 Their structure is analogous to native ECM fibrils, and they can be similarly arranged to create hierarchically complex scaffolds to recapitulate a variety of tissue architectures. 16 Microfiber scaffolds also provide provisional structural and mechanical support, topographic cues, and biochemical signaling cues to direct cell-mediated tissue regeneration. 16 Fibrin microthreads are a microfiber scaffold whose cylindrical form mimics native ECM fibrils, promoting cellular alignment and guided tissue regeneration.…”

“…16 Microfiber scaffolds also provide provisional structural and mechanical support, topographic cues, and biochemical signaling cues to direct cell-mediated tissue regeneration. 16 Fibrin microthreads are a microfiber scaffold whose cylindrical form mimics native ECM fibrils, promoting cellular alignment and guided tissue regeneration. 3,4,6,7,[17][18][19][20] Fibrin, the bioactive provisional matrix protein responsible for blood clotting, recruits cells that direct wound healing and functional tissue regeneration, making it a beneficial scaffold material.…”

“…35,37 In addition, future work to hierarchically assemble these microthreads into complex 3D scaffolds such as composites, braids, and bundles will allow us to further optimize bulk scaffold mechanics and mimic tissue-specific ECM architecture such as skeletal muscle, ventricular myocardium, tendon, ligament, or skin. 16 HRP-catalyzed crosslinking further mediated the resistance of fibrin microthreads to proteolytic degradation. Although fibrin microthreads have robust mechanical properties compared with fibrin hydrogels, fibrin remains susceptible to cellmediated compaction and rapid degradation by proteinases when implanted in vivo.…”

Utility of extracellular matrix powders in tissue engineering

“…3 The interactions between cells and ECM motifs are highly important in determining cell fate and maintaining cellular phenotyp. 4 In order to induce formation of the correct tissue at a specific site, the structure, composition, and source of ECM used must be considere. 5 The macrostructure of ECM can be modified to suit the intended application.…”