The Synergy of Biomimetic Design Strategies for Tissue Constructs

Abstract

The regeneration and repair of complex structures, interfaces, and mechanical properties present in natural tissues remains a challenge. To move beyond simplified tissue engineered constructs, nature is a source of inspiration for complex, hierarchical scaffold designs. Recent advances in additive manufacturing allow for increasingly complex fabrication of architectures that better mimic the multiscale structure-function relationship found in natural tissues. In this review, scaffold-based and scaffold-free approaches and the synergistic use of fabrication technologies (two things make a third) to produce more biomimetic implants are described. Recent advanced scaffold designs such as auxetic mechanical metamaterials and induced fibrillar alignment are highlighted. Next, the pre-programmed assembly of spheroids, tissue strands, and other modular building blocks without the need for permanent exogenous scaffold support are discussed. Furthermore, the application of hybridized manufacturing processes to fabricate hierarchical functional constructs is outlined for the osteochondral unit, vascular grafts, and peripheral nerves.

Cell-free and cytokine-free self-assembling peptide hydrogel-polycaprolactone composite scaffolds for segmental bone defects

“…12 Hybrid design strategies for tissue constructs showed synergetic effects. 13 In this study, a biomimetic extracellular matrix (ECM) composite scaffold composed of a self-assembling peptide hydrogel (SAPH) and 3D-printed polycaprolactone (PCL) scaffold was designed (Fig. 1).…”

Scaffold‐Free Tracheal Engineering via a Modular Strategy Based on Cartilage and Epithelium Sheets

“…On these bases, cells were encapsulated in ECM and fused to generate an operable macrostructure, which could be utilized to mimic the desired shape, complex morphology, and physiological tasks of natural tissues. [29][30][31][32] Herein, auricular chondrocytes were densely stacked to induce self-assembly and form operable cartilage sheets (Cart-S), in which chondrocytes could grow in a 3D pattern to promote intercellular communication and maintain phenotypic stability. The Cart-S was further laminated and reshaped to construct a cartilage tube, and the feasibility of the cartilage tube to serve as the main load-bearing structure was explored along with the morphology and differentiation of the inner chondrocytes.…”

A One‐Stone‐Two‐Birds Strategy for Osteochondral Regeneration Based on a 3D Printable Biomimetic Scaffold with Kartogenin Biochemical Stimuli Gradient

“…With regard to the anisotropic and hierarchical native osteochondral tissue in matrix composition and cell types, the regeneration requires the involvement of distinct layers including articular cartilage and subchondral bone. [5] Hence, in developing the osteochondral tissue engineering technique, the creation of a microenvironment appropriate for both the cartilage and the bone tissues (a biphasic construct for example) to restore will achieve superior outcomes in the treatment of osteochondral defects. [5,6] Hydrogels are the most ubiquitously applied scaffold patterns in tissue engineering because of their compositional and functional diversities and their characteristic similarity to the native extracellular matrix network.…”

“…[5] Hence, in developing the osteochondral tissue engineering technique, the creation of a microenvironment appropriate for both the cartilage and the bone tissues (a biphasic construct for example) to restore will achieve superior outcomes in the treatment of osteochondral defects. [5,6] Hydrogels are the most ubiquitously applied scaffold patterns in tissue engineering because of their compositional and functional diversities and their characteristic similarity to the native extracellular matrix network. [7] For chondral and osteochondral damages with irregular shapes, injectable and 3D printable hydrogels are advantageous for the good integration to the adjacent tissue as well as the minimal invasiveness during operation.…”