Advancements in tissue engineering and regenerative medicine and a surge in market demand over the last two decades have led to the development of a number of biological and synthetic scaffolds. These scaffolds have been used, to varying degrees of success, in tissue repair in both pre-clinical studies and clinical applications. While they share many characteristics, biological and synthetic scaffolds possess distinct properties that from a manufacturing and regulatory perspective. The FDA defines the ideal scaffold as:
“Biocompatible, biodegradable, [able to] promote cellular interactions and tissue development and possess proper mechanical and physical, biological and chemical properties.”
Technical scaffold demands are generally summarized as the 4Fs: Form, Function, Fixation, and Formation. Creating a scaffold that meets all these requirements is a challenging task. Clinical trial data with long-term follow-up studies is lacking for most currently available scaffolds, particularly those derived from animal tissue (Hollister and Murphy; Tissue Eng Part B Rev. 2011 December; 17(6): 459–474).
Biological scaffolds are generally derived from mammalian sources – namely human, bovine, porcine and equine – and tissues such as heart valves, skin, nerves, skeletal tissue and ligaments. These scaffolds are processed to remove lipids and fat deposits, they are then cross-linked and sterilized. Ideal biological scaffolds possess a surface chemistry that is biologically active and promotes tissue growth and cellular proliferation. Extracellular matrix scaffolds, with biological molecules and cells arranged in 3D patterns, have a composition which corresponds to the tissue from which they are derived. Commercial examples of biological ECM scaffolds include AlloDerm (derived from human skin, LifeCell),TissueMend (fetal bovine skin, TEI Biosciences) and GraftJacket (human skin, Wright Medical Tech). Biological scaffolds are generally recognized to have good biocompatiblity and degrade slowly over time. However, they possess numerous drawbacks particularly from a manufacturing perspective: biological materials can vary from batch to batch, can be hard to source, are disease-prone and can break down too quickly in the body.
Synthetic scaffolds, on the other hand, are fabricated from resorbable on non-resorbable polymers, such as polypropylene, polyester, silicone and carbon. Companies such as Akron manufacture robust polymer scaffolds (see our patent-pending AK Polyfibers).Their main advantages are that they provide strong tissue reinforcement, but may cause a foreign body reaction, which can result in serious complications. From a manufacturing perspective, they are advantageous because they can be produced in bulk fairly easily and can be engineered to degrade at a specific rate. While their limited biocompatibility lowers the risk of an immune response or cross-contamination, they are also less “agreeable” with native human tissue, and can thus promote cell proliferation less efficiently. These scaffolds can be coated with cells. Cell-derived coatings have been recently developed for polymeric scaffolds – such as mesenchymal stem cell coatings – which improve on the major drawbacks of fully biological scaffold matrices (Decaris et al., Tissue Eng Part A. 2012 Oct;18(19-20):2148-57).
In order to marry the best advantages from both sources, tissue engineers have been developing so-called hybrid scaffolds, which combine biological and synthetic aspects. Electrospun polymer-chitosan scaffolds are a promising example of such hybrid scaffolds.
FDA guidelines, generally, require scaffold products to abide by a number of regulations governing tissue engineered combination products (some basic guidelines are given in Early Development Considerations for Innovative Combination Products), though regulation is a complex issue. This includes material selection and fabrication, sterility assurance and resorption profiles, to name a few. Standard biocompatibitility tests for scaffolds may include cytotoxicity, irritation, carcinogenicity and genotoxicity among many others. Depending on the source of material, guidelines increase in specificity and complexity. For instance, polymeric scaffolds made of silicone might find an easier path toward approval due to the broad level of characterization of the raw material, unlike tissue-based scaffolds which require additional regulation with respect to tissue source, sterility, viability etc. The American Society for Testing and Materials has issued a Standard Guide for Characterization and Testing of Biomateral Scaffolds Used in Tissue-Engineered Medical Products.
Many of the scaffolds that have already been commercialized for numerous applications such as wound repair are relatively simple. For the next generation of scaffolds to have the ability to deliver drugs, cells and genes will require extensive research, testing and, ultimately, clinical trials.