Mimicking biological functionality with polymers for biomedical applications

Abstract

The vast opportunities for biomaterials design and functionality enabled by mimicking nature continue to stretch the limits of imagination. As both biological understanding and engineering capabilities develop, more sophisticated biomedical materials can be synthesized that have multifaceted chemical, biological and physical characteristics designed to achieve specific therapeutic goals. Mimicry is being used in the design of polymers for biomedical applications that are required locally in tissues, systemically throughout the body, and at the interface with tissues.

Figure 1 ∣. Strategies to create synthetic environments that mimic tissues.

a, Cell-matrix mimics. Synthetic hydrogels made of polymers can be modified with peptides or proteins (such as growth factors) and cell-sensitive degradable crosslinks that mimic many of the properties of the native tissue extracellular matrix (ECM). b, Cells often live in communities, so it can be useful to mimic cells by attaching surface proteins to a hydrogel. c, The mechanical properties of the hydrogel can be controlled by varying the crosslinking density or using chemistries that change the mechanical properties independently of ligand presentation; by metal ligand chemistry from the mussel; or by varying the ionic crosslinking density in alginate hydrogels derived from seaweed. d, The natural ECM from tissues can be processed to remove cells, and the remaining matrix can be processed into different scaffold forms, such as particles, tubes and sheets. e, A cell can migrate into a polymeric material where it is ‘educated’ by signals embedded in the scaffold before leaving to perform a particular function in the body. (Figure reproduced with permission from refs , , and .)

Figure 2 ∣. Biomimetic polymeric nanostructures can be constructed to mimic the geometries of biological viruses for systemic delivery.

Viruses can have spherical, rod-like, worm-like and ellipsoidal shapes, as shown here: a, adenovirus; b, tobacco mosaic virus; c, Ebola virus; d, Acidianus convivator. e–h, These viruses are mimicked respectively by polyethylene glycol-b-polyphosphoramidate/DNA polyelectrolyte complex nanoparticles with spherical (e), rod-like (f) and worm-like (g) shapes, and by ellipsoidal poly(lactic-co-glycolic acid)-based nano artificial antigen-presenting cells with an aspect ratio of 2 (h). Non-spherical shapes are shown to have enhanced efficacy for the intracellular delivery of DNA and the extracellular presentation of protein. (Figures are reproduced with permission from refs , , - and .)

Figure 3 ∣. Biomimetic materials for the design of tissue adhesives and device coatings.

a, Geckos can walk up walls and hang upside down with the help of pillars and setae on their feet^,. b, Mussels use chemistry that functions in a wet environment to create a powerful adhesive. Mussel coatings can be applied to gecko pillars to create sticky materials that function in a physiological environment^,,,. c, Sandcastle worms create 3D structures in sea water by using adhesives organized into vesicles that can be replicated with biocompatible chemistries to synthesize medical adhesives. d, The surface geometries of beetles, cactus needles and pitcher plants create a hydrophobic layer that can be captured in device coatings^,. e, Lubricin protein can be mimicked by bottlebrush polymers to lubricate tissues such as articular cartilage. DP, degree of polymerization.

Figure 4 ∣. Synthetic polymer structures used for active interaction with immune cells.

a,b, Scaffolds. Immune cells trapped or migrating into scaffolds can be manipulated by signals embedded in the material (a). Scaffolds can also include elements that are processed by antigen-presenting cells (APCs) (b) and presented to T cells where they can induce the desired response. c,d, Particles. The physical properties of polymeric nanoparticles, such as shape, and their chemical properties, such as protein surface density (c), can be engineered to stimulate T cells (d). Polymeric particles function as artificial APCs by mimicking major histocompatibility complexes (MHC) that bind with specific peptide antigen and T-cell receptors, as well as T-cell co-stimulatory molecules.