A review of combined experimental and computational procedures for assessing biopolymer structure-process-property relationships

Abstract

Tailored biomaterials with tunable functional properties are desirable for many applications ranging from drug delivery to regenerative medicine. To improve the predictability of biopolymer materials functionality, multiple design parameters need to be considered, along with appropriate models. In this article we review the state of the art of synthesis and processing related to the design of biopolymers, with an emphasis on the integration of bottom-up computational modeling in the design process. We consider three prominent examples of well-studied biopolymer materials - elastin, silk, and collagen - and assess their hierarchical structure, intriguing functional properties and categorize existing approaches to study these materials. We find that an integrated design approach in which both experiments and computational modeling are used has rarely been applied for these materials due to difficulties in relating insights gained on different length- and time-scales. In this context, multiscale engineering offers a powerful means to accelerate the biomaterials design process for the development of tailored materials that suit the needs posed by the various applications. The combined use of experimental and computational tools has a very broad applicability not only in the field of biopolymers, but can be exploited to tailor the properties of other polymers and composite materials in general.

Fig. 1

Possible structures and technical applications of the materials silk, elastin and collagen. The dotted line shows an example of the versatility of silk and the multiple possible applications. Courtesy for images is as follows: Spider is from David Maiolo uploaded on 14.08.2011 on Wikipedia under the CC BY-SA 3.0 license. Silk cocoon, gel, sponge, fiber and electronic device are adapted from Omenetto and Kaplan [111]. Lungs from “jemsweb” on 06.07.2007 uploaded via flickr under the CC BY-SA 2.0 license. Elastin molecule is adapted from Baldock et al. [160]. Copyright 2011 National Academy of Sciences, USA. Collagen molecule is adapted from Gautieri et al. [161]. Microspheres are reprinted from Wang et al. [162] with permission from Elsevier. Particles are reprinted from Lammel et al. [115] with permission from Elsevier. Film is adapted from Krishnaji et al. [163]. Tube is reprinted from Lovett et al. [164] with permission from Elsevier. Photonics is from Fiorenzo Omenetto. Drug delivery is reprinted from Tsioris et al. [165]. Collagen scaffold is reprinted from Sachlos et al. [166] with permission from Elsevier. Microfluidic device is reprinted with permission from Bettinger et al. [167].

Fig. 2

Experimental and computational methods to study the structure and properties of hierarchical biopolymers according to the length scale they address. Note how the different approaches work on distinct scales. In the bottom-up design of biopolymers all hierarchical levels must be considered. Therefore, only an integration of these approaches will allow full control of biopolymer design. Modeling could fill in the gaps in understanding processes that cannot be analyzed experimentally. Abbreviations are as follows: FEM: Finite Element Method, CFD: Computational Fluid Dynamics, MD: Molecular Dynamics, QM: Quantum Mechanics, DFT: Density Functional Theory, CCSD(T): Coupled Cluster Method, ROMP: Ring Opening Metathesis Polymerization, ATRP: Atom Transfer Radical Polymerization, SPPS: Solid Phase Peptide Synthesis, FTIR: Fourier Transform Infrared Spectroscopy, DLS: Dynamic Light Scattering, CD: Circular Dichroism Spectroscopy, XRD: X-ray Diffraction, MicroCT: Microtomography, AFM: Atomic Force Microscopy, SEM: Scanning Electron Microscopy, TEM: Transmission Electron Microscopy.

Fig. 3

The four main fields of study of biopolymer design: sequence, structure, process condition and properties. The examples show silk as a versatile biopolymer. The arrows show the relationships between the fields of study. Examples for studies on these relationships are shown in Table 4. Courtesy for images is as follows: Silk representation is adapted from Ref. [143]. Stress–strain plot is reprinted with permission from Ref. [168], copyright © 2011 American Chemical Society. Microfluidic device is reprinted with permission from Ref. [32], copyright © 2011 American Chemical Society.