These smart materials are key to advancing regenerative medicine

Next-generation smart materials will enhance the efficacy of regenerative therapies while minimizing side effects.

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

Central to the success of regenerative medicine are 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 crucial 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, ensuring precise and controlled delivery to target tissues. This capability enhances the efficacy of regenerative therapies while minimizing side effects and improving patient outcomes.

Smart materials can adapt to various physical, chemical, and biological conditions, promising to revolutionize treatments and enable new advances in regenerative medicine. By understanding and harnessing these materials, scientists and doctors can create more effective, dynamic, and personalized medical treatments.

Sequence-defined polymers

The next era of smart materials for biomedical applications is largely dependent on the development of sequence-defined polymers (SDP), which are an emerging class of synthetic polymers with a regulated sequence of monomers. Smart materials support dynamic structures and devices and must be able to adapt to the changing needs of the biological tissue environment. Smart materials may be responsive to diverse microenvironmental stimuli, including physical (temperature, light, electric or magnetic fields), chemicals (covalent and ionic bonds, van der Waal and hydrophobic interactions), and biological (enzymes, receptors, etc.).

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

Tunable biomechanics

Imagine you have a sponge that can change its firmness. Sometimes it’s soft and squishy, ​​and other times it’s firm and supportive. This ability to change how stiff or flexible it is based on what’s needed is similar to what we call “tunable biomechanical properties” in biological tissues.

Tunable biomechanical property is a required characteristic of smart materials relevant to regenerative medicine. We now have a wide range of hydrogels in which in situ tuning of mechanical properties is possible. Modulation of polymer network rigidity makes such hydrogel highly valuable for regenerative medicine applications.

ATP binding may make a soft hydrogel rigid. This is achieved by the integration of an aptamer sequence which is capable of ATP-specific binding into the backbone of the cross-linking network of the hydrogel. Upon binding of ATP, the aptamer’s conformation changes from a random coil to a stable structure thus increasing rigidity of the hydrogel.

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

Increased rigidity of the hydrogel may enlarge the mesh size of the matrix, thus increasing the diffusion rate of nutrients and growth factors. At the same time, such increased mesh size may facilitate drainage of metabolic waste products in three-dimensional tissue culture. 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 outstanding interest in developing regenerative medicine solutions. Such materials are characterized by unique structural reconfiguration features that allow them to adapt as per the provided environmental conditions and can be designed for their enhanced biocompatibility.

Imagine if you had a piece of material that could “remember” a shape and return to it when you wanted. This concept is the basis for shape memory polymers (SMPs) and shape memory alloys (SMAs), which are becoming very important in the field of tissue engineering.

Self-healing SMPs and SMAs may be used as actuators for soft robotics, chromogenic systems for liquid crystals, self-developing structures, and active origami. Origami-inspired approaches have proven to be useful for biomedical applications such as developing voluminous structures with the ability to conform to biosystems, shapeshifting 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 blends of polyurethane and polyvinylchloride display shape memory effects.

Liquid crystal elastomers

Material that combines the unique properties of liquid crystals (like those found in your TV or smartphone screens) with the stretchy, flexible nature of rubber is known as a liquid crystal elastomer (LCE).

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

Because of their actuation and shock absorption properties they have proven to be useful for the development of artificial tissue, biological sensors, and cell scaffolds. Pre-patterned LCE is valuable for artificial morphogenesis wherein nanoscale details of molecular organization are translated into a 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 crucial role in many everyday technologies and are essential in the emerging discipline of biomedical engineering.

Advances in soft material science have led to the production of MSM which undergo reprogramming deformations under magnetic fields. MSM produces magnetic soft robots which are superior to traditional rigid robots because of distinct mechanical compliance, tether-free actuation, and biocompatibility.

Covalent adaptable networks

Covalent adaptable networks (CANs) are polymer networks that possess reversible covalent cross-links with the capacity for adapting to an externally applied stimulus. CANs enable the rational design of structural materials possessing dynamic characteristics for specialty applications.

A hydrazone poly(ethylene glycol) hydrogel CAN modulate extracellular matrix deposition for cartilage tissue engineering. In this application, CAN achieves tunable viscoelastic properties and enables the study of how chondrocyte proliferation and matrix deposition may vary with the time-dependent material properties of CAN.

Chandan K. Sen, Ph.D., MS, is a world-renowned regenerative medicine expert and pioneer of novel wound care technologies who joined the University of Pittsburgh in 2023 as associate vice chancellor for life sciences innovation and commercialization, health sciences, and also serves as director of the university’s McGowan Institute for Regenerative Medicine (MIRM). He is responsible for accelerating momentum in research areas that are key to the future of the Pittsburgh region, and for driving collaboration with local and national academic and industry partners to speed scientific discoveries to patients and the marketplace.

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