Designing Smart Biomaterials for Tissue Engineering

Abstract

The engineering of human tissues to cure diseases is an interdisciplinary and a very attractive field of research both in academia and the biotechnology industrial sector. Three-dimensional (3D) biomaterial scaffolds can play a critical role in the development of new tissue morphogenesis via interacting with human cells. Although simple polymeric biomaterials can provide mechanical and physical properties required for tissue development, insufficient biomimetic property and lack of interactions with human progenitor cells remain problematic for the promotion of functional tissue formation. Therefore, the developments of advanced functional biomaterials that respond to stimulus could be the next choice to generate smart 3D biomimetic scaffolds, actively interacting with human stem cells and progenitors along with structural integrity to form functional tissue within a short period. To date, smart biomaterials are designed to interact with biological systems for a wide range of biomedical applications, from the delivery of bioactive molecules and cell adhesion mediators to cellular functioning for the engineering of functional tissues to treat diseases.

Keywords: extracellular matrix; smart materials; stimuli responsive polymer; tissue engineering.

Figure 1

Smart polymer biomaterials for tissue engineering applications: (a) Representation of elastic modulus of various tissues in consideration to design a smart scaffold; (b) stimuli responsive system (∆T: variation of temperature change, ∆pH: variation of pH, ∆λ: variation of wave length, and ∆E: variation of electric field); (c) structures of some synthetic and natural smart polymers; and (d) novel scaffold of poly(2-methoxyethyl acrylate) (PMEA)—hydrated PMEA forms intermediate water, which affects the protein adsorption, as well as cell adhesion, proliferation, and differentiation.

Figure 2

Stimuli-responsive polymeric biomaterials for TE applications: (a) CS/PEI, pH responsive hydrogel scaffold, scanning electron microscope image hydrogels frozen in liquid nitrogen and freeze-dried (i), a confocal image of HeLa cells (labeled with CellTracker Green) grown within the hydrogel (day 21) (ii), human fetal skeletal cells (labeled with CellTracker Green) grown within the hydrogel on day 7 (iii) and day 28 (iv); (b) influence of photodegradable dynamic microenvironment on chondrogenic differentiation of hMSCs was verified by immunostaining for the hMSC marker CD105 (fluorescein isothiocyanate (FITC), green) and the chondrocyte marker COLII (tetramethyl rhodamine isothiocyanate–labeled, red), cells did not produce COLII on day 4 (left), almost half of the cells with peptide sequence (Arg-Gly-Asp-Ser (RGDS)) strongly expressed CD105, and the other half produced COLII (right) on day 21; (c) self-assembly of complementary peptides hydrogels; (i) TEM image of P₁₁–13/P₁₁–14 peptide fibrils and fibers, prepared at pH 7.4, primary human dermal fibroblasts grown within hydrogel and their histological images P₁₁–13/P₁₁–14 hydrogel after 14 days of culture (ii,iii). Black arrows indicate possible cell remnants of black, circular aggregates on some fibers. P₁₁-4 hydrogel with primary human dermal fibroblasts (red arrows) after 14 days of culture (iv) showing Neo-ECM deposition; (d) bioresorbable scaffolds fabricated from polymer blend (CS/Polyvinyl acetate (PVAc)/PLLA: 50/25/25) for bone TE; (i) SEM image of scaffold prepared by freeze drying using a solvent-evaporation technique showing 3D porous network structure, immunostaining for osteogenic bone-matrix proteins of STRO-1 + cells cultured on the scaffold (in vitro), cell nuclei are stained with DAPI (green) and each bone matrix protein is stained by the Alexa 594 fluorochrome-conjugated secondary antibody (red). Confocal microscopic images show Collagen type I (ii, iii), osteopontin (OPN) (iv), bone sialoprotein (BSP) (v) and osteonectin (ONN) (vi). (d) (vii–xi) Quantitative μ CT analysis for bone tissue regeneration of selected regions of interest within the osteotomy defect after 28 days. Enhanced bone formation is demonstrated in both scaffold groups (without and with STRO-1 + cells, respectively) when compared to the control group. Assessment of new bone regeneration in the defect regions in femora of mice at 28 days following implantation, using indices of bone volume/total volume (BV/TV) (x) and trabecular number (Tb No) (xi). Results are presented as mean ± SD, n = 4 per group, ∗ = p < 0.05, ∗∗ = p < 0.005. (a) reproduced with permission [40]. Copyright 2009, Wiley-VCH Verlag, Germany. (b) Reproduced with permission [65]. Copyright 2009, Science. (c) Reproduced with permission [47]. Copyright 2012, Wiley-VCH Verlag. (d) Reproduced with permission [12]. Copyright 2013, Wiley-VCH Verlag, Germany.