Stem cell-based tissue engineering with silk biomaterials

Silk is an excellent material to work with in tissue engineering as it is biocompatible, lightweight, strong, elastic, and even thermally stable up to 250°C. Biomaterial scaffolds form an important structural basis for the in vitro and in vivo growth of a variety of engineered tissues. They must be biocompatible, biodegradable, effectively mimic cellular environment (i.e. support cell attachment, migration, etc.), and be versatile in processing options to alter structure and morphology related to tissue-specific needs.

As a 2D film, silk is comparable to collagen films in terms of supporting attachment, spreading and proliferation of fibroblasts. Silk from cocoon fibers was found to support the attachment and growth of human and animal cell lines, due to the positively-charged residues in the fibroin sequence and the negatively charged surface of mammalian cells. The biomedical applications of silk fibroin films could be broadened by surface modifications with RGD or specific growth factors, as well as by blending with other natural or synthetic polymers, like cellulose, collagen, or polyacrylamide.

Hydrogels can be formed from regenerated silk fibroin solution by sol-gel transition in the presence of acid, ions, and other additives. As a hydrogel, silk has applications in guided bone repair, drug release/delivery, and cartilage tissue engineering. In one experiment, silk fibroin hydrogels were used to repair confined, critical-sized cancellous bone defects in a rabbit.

In the form of a non-woven mat or net, silk is incredibly strong and functions well in wound dressing, skin repair, and tissue engineering. It has been shown that non-woven micro-fibrous nets support the adhesion, proliferation, and cell-cell interactions of a wide variety of human cell types including epithelial cells, endothelial cells, glial cells, keratinocytes, osteoblasts, and fibroblasts. Silk fibroin mesh implants were shown to be highly biocompatible and integrated with the surrounding tissue with no apparent degradation. Non-woven nano-fibrous nets and mats are also of interest for biomedical applications because of the material’s high surface area. It supported the attachment, spreading, and proliferation of human bone marrow stromal cells, keratinocytes and fibroblasts.

However, perhaps the most versatile and useful forms silk fibroin is able to take is a 3D porous sponge. Not only is this form able to be molded into endless shapes and structures, it is very strong and contains high porosity and poor interconnectivity. This structure is ideal for bone and cartilage tissue engineering. One study explored the potential of native silk fibroin fibers as 3D scaffolds for tissue engineering of ACL in cultures with dynamic mechanical loading. After weave together these fibers in a manner mimicking the structural assembly of the ALC, MSC were successfully supported in their attachment, spreading, proliferation and differentiation. A great variety of other “yarn” 3D structures have been created with different weaving patterns and subsequent mechanical properties. 3D porous silk fibroin scaffolds have also been used for MSC-based bone tissue engineering; it provided an appropriate environment for MSC’s to proliferate and differentiate and showed promise for repair of critical sized bone defects. 3D porous silk fibroin sponges are also useful in cartilage tissue engineering. Adult articular cartilage has limited self-repair capacity, and previous uses of collagen- and alginate-based scaffolding proved insufficient due to rapid degradation. The useful combination of high strength, porosity, processability, good biocompatibility and ability to support cell adhesion, proliferation, and differentiation suggests 3D porous silk fibroin scaffolds are prime candidates for stem cell- and chondrocyte-based cartilage tissue engineering.

I feel that this paper provides an excellent example of the crucial interplay between materials science and tissue engineering. Adequate scaffolding is becoming a necessity in modern-day tissue engineering, and a variety of materials have been studied and used for supporting cell growth and differentiation. However, none have proven as versatile and innately biocompatible as silk fibroin. The diversity of tissue-modeling possibilities and medical applications allowed by this one material is astounding. I also love how this paper provides an instance of biologists, chemists, and engineers collaborating to create useful scientific tools by borrowing a preexisting natural entity. One of my favorite things about being a bioengineer is how we are allowed the unique opportunity to be inspired by nature in a realm of synthetic and technological possibilities. Who knew a cocoon-material could one day save your life?