Towards the design of 3D multiscale instructive tissue engineering constructs: Current approaches and trends

Abstract

The design of 3D constructs with adequate properties to instruct and guide cells both in vitro and in vivo is one of the major focuses of tissue engineering. Successful tissue regeneration depends on the favorable crosstalk between the supporting structure, the cells and the host tissue so that a balanced matrix production and degradation are achieved. Herein, the major occurring events and players in normal and regenerative tissue are overviewed. These have been inspiring the selection or synthesis of instructive cues to include into the 3D constructs. We further highlight the importance of a multiscale perception of the range of features that can be included on the biomimetic structures. Lastly, we focus on the current and developing tissue-engineering approaches for the preparation of such 3D constructs: top-down, bottom-up and integrative. Bottom-up and integrative approaches present a higher potential for the design of tissue engineering devices with multiscale features and higher biochemical control than top-down strategies, and are the main focus of this review.

Evaluation of the direct effects of poly(dopamine) on the in vitro response of human osteoblastic cells

“…The modern history of biomedical research and regenerative medicine has been characterized by a concerted effort aimed at developing strategies to precisely control the interactions between biomaterials and the surrounding biological milieu to ultimately guide cellular events along predetermined pathways. [1][2][3] The motivation that has been propelling such collective endeavour is the evidence that the physicochemical environment of surfaces at the micro-and nanoscale not only controls cell behaviour in vitro, 4 but also influences the in vivo outcome of implanted devices. 5,6 The knowledge of how cells sense and respond to surfaces has rapidly progressed in the last two decades, thanks also to the concomitant development of nanotechnology-based approaches which provided researchers with novel strategies to nanoengineer functional biomaterials, 4 and increasingly more sophisticated toolboxes to evaluate the biological response at the molecular and cellular level (e.g.…”

Electrospinning of natural polymers for advanced wound care: towards responsive and adaptive dressings

“…These approaches are under examination in other areas of regenerative medicine. [121][122][123] For instance, bimodal and multiphasic scaffolds with controlled porosity and surface area have been obtained by the coexistence of micro-and nanoelements, and used for enhancing cell infiltration. 121 When hierarchical constructs are then coupled with cell therapies, a more homogeneous distribution of cells within the scaffold can …”

3D cell bioprinting of self-assembling peptide-based hydrogels

“…They have enhanced cell-cell and cell-ECM (extracellular-matrix) interactions, 3D cell spatial distributions, higher cell densities and fully interconnected pore networks for vascularization and media diffusion [4]. The benefits, when compared to cell-based strategies, are clear and extensively reported in the literature [5][6].…”

“…However this approach is still hindered by the inability of the scaffold to promote homogeneous cell distributions, or to mimic the native ECM microenvironment [6]. To address these issues, a ''bottom-up'' approach, combining Bioprinting and highly hydrated polymers with encapsulated cells have been investigated [4]. The range of manufacturing systems available is wide and can be classified into extrusion-based; binder jetting (or Ink Jet); and vat photo-polymerization (or laser-based) categories [7][8][9].…”