New generations of synthetic biomaterials are being developed at a rapid pace for use as three-dimensional extracellular microenvironments to mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies. Recent advances include nanofibrillar networks formed by self-assembly of small building blocks, artificial ECM networks from protein polymers or peptide-conjugated synthetic polymers that present bioactive ligands and respond to cell-secreted signals to enable proteolytic remodeling. These materials have already found application in differentiating stem cells into neurons, repairing bone and inducing angiogenesis. Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.

https://sisu.ut.ee/sites/default/files/quantum/files/synthetic_biomaterials_as_instructive_extracellular_microenvironments_for_morphogenesis_in_tissue_engineering_lutolf_m.p_hubbell_j.a_2005_0.pdf

Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering

Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.

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Hydrogels in regenerative medicine

The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here we discuss the basic physical concepts necessary to understand the consequences of liquid-like states for biological functions.

https://www.annualreviews.org/doi/pdf/10.1146/annurev-cellbio-100913-013325

Liquid-liquid phase separation in biology.

Novel crosslinking methods to design hydrogels

▪ Abstract Hydrogels are cross-linked hydrophilic polymers that can imbibe water or biological fluids. Their biomedical and pharmaceutical applications include a very wide range of systems and processes that utilize several molecular design characteristics. This review discusses the molecular structure, dynamic behavior, and structural modifications of hydrogels as well as the various applications of these biohydrogels. Recent advances in the preparation of three-dimensional structures with exact chain conformations, as well as tethering of functional groups, allow for the preparation of promising new hydrogels. Meanwhile, intelligent biohydrogels with pH- or temperature-sensitivity continue to be important materials in medical applications.

/pdf/physicochemical-foundations-and-structural-design-of-139fyql4ch.pdf

Physicochemical foundations and structural design of hydrogels in medicine and biology.

Hydrogels of an interpenetrating polymeric network (IPN) composed of the temperature-sensitive poly(N-isopropylacrylamide) (PNIPAAm) and the pH-sensitive poly(methacrylic acid) (PMAA) were prepared by a sequential UV polymerization method. The IPN hydrogels were characterized for their temperature- and pH-responsive behavior by equilibrium swelling studies, oscillatory swelling studies, and differential scanning calorimetry. The permeability of these IPNs has been investigated under various pH and temperature conditions. The results showed that these hydrogels exhibited a combined pH- and temperature-sensitivity at a temperature range of 31−32 °C and a pH value of approximately 5.5. Permeation study results indicate a significant size exclusion behavior while model drugs with different sizes permeate through the IPN membranes. The permeability of the IPN membrane can be significantly affected by varying the pH and temperature conditions.

Synthesis and Characterization of pH- and Temperature-Sensitive Poly(methacrylic acid)/Poly(N-isopropylacrylamide) Interpenetrating Polymeric Networks

The molecular interactions between the component networks in poly(methacrylic acid)/poly(N-isopropyl acrylamide) (PMAA/PNIPAAm) interpenetrating polymer networks (IPNs) were investigated using attenuated total reflectance (ATR)-Fourier transform IR (FTIR) spectroscopy. Hydrogen-bond formation was noted between the carboxyl groups of PMAA and the amide groups of PNIPAAm. The ATR-FTIR results showed shifts in the carboxylic and amide groups, indicating the existence of hydrogen bonding between these two individual networks within the IPNs. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 1077–1082, 2001

Jing Zhang

Papers

Physicochemical foundations and structural design of hydrogels in medicine and biology.

Synthesis and Characterization of pH- and Temperature-Sensitive Poly(methacrylic acid)/Poly(N-isopropylacrylamide) Interpenetrating Polymeric Networks

Molecular interactions in poly(methacrylic acid)/poly(N-isopropyl acrylamide) interpenetrating polymer networks

Interpenetrating Polymeric Networks

Interpenetrating Polymer Networks (IPNs): Hydrogels