Tissue Engineering and Biomaterials

Innovations and Challenges

Tissue Engineering (TE) has witnessed significant advancements over the past decade, particularly with the introduction of artificial biomaterials as alternatives to auto-transplants. Key characteristics of these materials include excellent biocompatibility and biodegradability. Despite their advantages, most materials currently employed in TE, primarily based on polyesters, face limitations in their application, especially as scaffolds. These limitations arise from their undesirably degradation characteristics and the formation of acidic degradation products, which can lead to tissue inflammation or even necrosis. As a result, there is a growing interest in alternatives to ester functionalities that demonstrate enhanced degradability.

Moreover, there is a demand for advanced polymer processing methods such as Additive Manufacturing. Photopolymers that exhibit both biocompatibility and biodegradability are emerging as promising candidates for TE applications. The ability to structure compounds using techniques like Stereolithography or Direct Laser Writing enables us to create constructs with complex geometries and high resolutions, mimicking the cellular structures found in natural materials like bone.

Current state-of-the-art compounds for these applications primarily utilize (meth)acrylate-based materials. However, methacrylates show low photoreactivity, while acrylates may engage in side reactions with proteins in the human body, which can lead to irritation and toxicity. The hydrolytic degradation of these materials can also lower local pH levels and result in the formation of non-excretable precipitates in the presence of calcium ions, making them less suitable for biomedical use. To address these issues, we have developed new monomers with varying polymerizable groups.

Despite their promise, one of the primary challenges remains the brittle behavior of these new materials, often due to uncontrolled chain growth polymerization. The incorporation of oligomeric building blocks also in combination with the concept of interpenetrating polymer networks offered us a pathway to enhance the toughness of these materials. Additionally, the introduction of moieties more susceptible to cleavage under physiological conditions aims to accelerate the degradation process.

The increasing number of patients with minor and major accidents necessitates improved fixation and adhesion between bone, implants, and scaffolds. The limited availability and versatility of biomimetic and biocompatible adhesives pose challenges, as current adhesives based on cyanoacrylates, polyurethanes, epoxy resins, and poly(methyl methacrylates) carry drawbacks such as allergic responses, insufficient mechanical strength, and toxic byproducts. Therefore, there is an urgent need for new biomimetic glues designed to bond tissue-to-tissue and tissue-to-implant interfaces. Given this critical role of adhesion in biological systems, we are exploring new strategies based on biological adhesion mechanisms. For instance, the phosphorylation of serine offers insights into effective adhesion strategies. A biomimetic phosphonate-containing block copolymer approach is being investigated to enhance surface adhesion. By combination of biomimetic adhesion motifs with above-mentioned polymerizable groups, we were able to generate in situcurable bone adhesives.

In the context of cardiovascular health, diseases of the cardiovascular system are leading causes of morbidity and mortality in Western countries. The estimated $503.2 billion cost of cardiovascular diseases and strokes in the United States in 2010 underscores the urgency for innovative solutions. Electrospinning (ES) has garnered attention for its ability to produce seamless, non-woven nanofibrous tubes that mimic the extracellular matrix (ECM), making them potentially suitable as vascular grafts. However, the materials currently in use often exhibit low compliancy or are non-degradable, highlighting the need for degradable TPUs.

Thermoplastic polyurethanes (TPUs), known for their good biocompatibility and elastomeric properties, are increasingly being researched for applications in vascular grafts as replacements for traditional materials like ePTFE and PET. While the avoidance of biodegradation has historically been prioritized, recent research seeks to utilize controlled biodegradation to stimulate tissue regeneration. By focusing on aliphatic isocyanates and ester-based chain extenders, we aim to develop TPUs with mechanical properties comparable to native blood vessels. Electrospun prostheses implanted in rats demonstrated promising outcomes, with compliant grafts and increased endothelial tissue growth observed in degradable grafts.

In summary, advancements in tissue engineering and biomaterials hold great promise for addressing critical medical challenges. The development of new photopolymers, degradable elatomers, and innovative adhesives is essential to enhance the effectiveness of tissue engineering applications. As our research continues to evolve, these innovations pave the way for improved treatments and better outcomes for patients across various medical fields, particularly in bone regenerative medicine and cardiovascular health. The ongoing exploration of biomimetic approaches and advanced polymer processing techniques will be fundamental in shaping the future of medical materials and their applications.


baudisLAB • Institute of Applied Synthetic Chemistry • Getreidemarkt 9/163, 1060 Vienna, Austria  stefan.baudis@tuwien.ac.at