These smart materials are key to the development of regenerative medicine

Next-generation intelligent materials will increase the effectiveness of regenerative therapies while minimizing side effects.

Author: Chandan K. Sen, McGowan Institute for Regenerative Medicine at the University of Pittsburgh

The key to the success of regenerative medicine is advanced materials that can seamlessly integrate with the body’s natural processes, facilitate tissue repair, and support the regeneration of functional organs. This is where the critical need for smart materials arises.

In addition to their role as scaffolds for tissue engineering, smart materials play a key role in drug delivery systems for regenerative medicine. They can be designed to release therapeutic agents in response to specific stimuli, such as changes in pH or enzyme activity, providing precise and controlled delivery to target tissues. This ability increases the efficacy of regenerative therapies while minimizing side effects and improving patient outcomes.

Smart materials can adapt to a variety of physical, chemical, and biological conditions, promising to revolutionize medical treatments and enable new advances in regenerative medicine. By understanding and using these materials, scientists and physicians can create more effective, dynamic, and personalized treatments.

Sequence-Defined Polymers

The next era of smart materials for biomedical applications largely depends on the development of sequence-defined polymers (SDPs), a new class of synthetic polymers with a tunable monomer sequence. Smart materials support dynamic structures and devices and must be able to adapt to the changing needs of the biological tissue environment. Smart materials can respond to a variety of microenvironmental stimuli, including physical (temperature, light, electric or magnetic fields), chemical (covalent and ionic bonds, van der Waal and hydrophobic interactions), and biological (enzymes, receptors, etc.).

SDPs enable intrinsic control of molecular structure, resulting in the generation of biomaterials that are programmable and thus meet a wide range of requirements for biomaterials compatible with regenerative medicine solutions. SDPs developed by phosphoramidite chemistry have been successfully used for 3D cell culture and organoid development. The growth of stem-like cells is highly sensitive to the biomechanical properties of their extracellular matrix.

Adjustable biomechanics

Imagine you have a sponge that can change its stiffness. Sometimes it’s soft and spongy, and other times it’s firm and supportive. This ability to change stiffness or elasticity based on need is similar to what we call “tunable biomechanical properties” in biological tissues.

Tunable biomechanical properties are a required feature of smart materials relevant to regenerative medicine. Today, we have a wide range of hydrogels in which in situ tuning of mechanical properties is possible. Modulation of the stiffness of the polymer network makes such a hydrogel extremely valuable for regenerative medicine applications.

ATP binding can stiffen the soft hydrogel. This is achieved by integrating an aptamer sequence that is capable of specifically binding ATP into the backbone of the hydrogel cross-linking network. Upon ATP binding, the aptamer conformation changes from a random coil to a stable structure, thereby increasing the stiffness of the hydrogel.

Another example of a biocompatible hydrogel with tunable mechanical properties are hydrogels formed by hybridization of DNA linkers tethered to polypeptides. In this case, adjusting the length of the DNA linkers or inserting mismatch sites allows modulation of the mechanical properties of the hydrogels.

The increased stiffness of the hydrogel can increase the mesh size of the matrix, thereby increasing the diffusion rate of nutrients and growth factors. At the same time, such increased mesh size can facilitate the drainage of metabolic waste products in three-dimensional tissue culture. The cross-linking formed by supramolecular interaction enables good reversible properties of these smart materials, thus enabling self-healing, stimuli-responsiveness, and shear thinning.

Shape memory materials

Shape memory materials are of great interest in developing regenerative medicine solutions. Such materials are characterized by unique structural reconfiguration features that allow them to adapt to environmental conditions and can be designed for increased biocompatibility.

Imagine having a piece of material that can “remember” its shape and return to it whenever you want. This concept is the basis for shape memory polymers (SMPs) and shape memory alloys (SMAs), which are becoming increasingly important in the field of tissue engineering.

Self-healing SMPs and SMAs can be used as actuators for soft robotics, chromogenic systems for liquid crystals, self-unfolding structures, and active origami. Origami-inspired approaches have proven useful in biomedical applications, such as developing bulk structures with the ability to conform to biosystems, changing shape from two-dimensional (2D) to three-dimensional (3D) structures, and biocompatibility.

SMPs produce medical devices such as stents and catheters. Polymers such as (meth)acrylates, polyurethanes and polyurethane/PVC blends exhibit shape memory effects.

Liquid crystal elastomers

A material that combines the unique properties of liquid crystals (like those found in TV and smartphone screens) with the stretchable, flexible nature of rubber is called a liquid crystal elastomer (LCE).

LCE represents a class of intelligent materials of interest in biomedical applications. LCE combines the elastic entropy behavior of conventional elastomers with the stimuli-responsive properties of anisotropic liquid crystals. LCE exhibits exceptional tensile properties and biocompatibility.

Due to their actuation and shock absorption properties, they have proven useful for developing artificial tissues, biosensors, and cell scaffolds. Preformed LCEs are valuable for artificial morphogenesis, where the details of molecular organization at the nanoscale are translated into the macroscopic shape of an organism.

Magnetically soft materials

Magnetically soft materials (MSM) are a class of magnetic materials that can be easily magnetized and demagnetized. These materials play a key role in many everyday technologies and are essential to the emerging discipline of biomedical engineering.

Advances in soft material science have led to the production of MSMs that undergo reprogramming deformations under the influence of magnetic fields. MSM produces magnetic soft robots that are superior to traditional rigid robots due to their pronounced mechanical compliance, wireless actuation, and biocompatibility.

Adaptive covalent networks

Covalent adaptable networks (CANs) are polymer networks that possess reversible covalent cross-links with the ability to adapt to an external stimulus. CANs enable the rational design of structural materials with dynamic properties for specialized applications.

Poly(ethylene glycol) hydrazone hydrogel CAN modulates extracellular matrix deposition in cartilage tissue engineering. In this application, CAN achieves tunable viscoelastic properties and allows the study of how chondrocyte proliferation and matrix deposition may change with time-dependent material properties of CAN.

Chandan K. Sen, Ph.D., MS, is a world-renowned expert in regenerative medicine and a pioneer in cutting-edge wound healing technologies who joined the University of Pittsburgh in 2023 as Associate Vice Chancellor for Innovation and Commercialization of Life Sciences, Health Sciences, and serves as Director of the University’s McGowan Institute for Regenerative Medicine (MIRM). He is responsible for accelerating momentum in research areas that are critical to the future of the Pittsburgh region and for driving collaboration with local and national academic and industry partners to accelerate scientific discovery for patients and the marketplace.

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The views expressed in this blog post are the author’s own and do not necessarily reflect the views of Medical Design & Outsourcing or its employees.