Natural Scaffolds

The hard work of making biomimetic materials

Natural biomaterials inherently provide biological signals and stimuli. When chosen properly, those natural properties aid in different types of healing. With some amount of hard work, synthetic materials can be modified to mimic some of these natural signals.

Cen Chen, et al., have produced an open access review in Biomaterials Research that summarizes the presentations from a 2015 Korea-China joint symposium on biomimetic materials. Their paper does not focus on natural materials, but illustrates the amount of work put in to making a material biomimetic, so that it acts like a natural biomaterial.

“…[R]esearch groups have briefly discussed recent research trends in biomimetic medical materials for tissue engineering such as 3D bioprinting, surface modification, nano/micro-technology and clinical aspects in tissue engineering of bone and cartilage.” — Cen Chen, et al.1

Research trends in biomimetic 3D printing

According to the authors, the main thrust in 3D bioprinting research is to mimic the extracellular matrix in bone and cartilage, both the nano/micro structure and chemical signaling. Examples given of these techniques are photo-printing that uses light to solidify a controlled area in a layer of hydrogel, fusion of particles in a powder bed with light or heat, and material extrusion or jetting.

Photo-printing and powder fusion face the challenge of finding non-toxic linking agents that provide structure while also being biodegradable. The extrusion of live cells often damages the cells from deformation of the printing nozzle and shear stress due to the force of extrusion. These problems cause cell aggregation and physical damage that can kill the cells or cause them to grow outside of the desired pattern.

The bioprinting of living cells currently creates features in the 100 micrometer to 1 millimeter range. This allows creation of biologically relevant porosity and surface structures. Apparently a large amount of the current research is trending towards finding new biocompatible polymers that can both safely encapsulate living cells and be an effective “ink.” Inorganic biomaterials, such as ceramics and calcium phosphates, are also being investigated as possible 3D printing inks for bone tissue engineering.

The authors conclude that while progress in 3D bioprinting of synthetic materials is being made, hurdles such as adequate printable materials, structural stability, biodegradation, and basic biocompatibility still have not been overcome.

Biomimetic trends in micro/nano-patterning technology

The two patterning technologies in use are top-down, which draws from semiconductor technologies with templates and lithography techniques, and bottom-up, which includes electrodeposition and self-assembly. Top-down approaches are comparatively slow and are associated with high fabrication costs. Bottom-up approaches are high-throughput techniques, but do not create precisely ordered materials.

Ironically, progress has been made in nano-templating by using natural materials to create templates for biomimetic synthetic materials. Diatoms — a type of algae — and galium aparine — also a common plant — have been used as templates for molding processes that fabricate micro and nano patterns.

The main challenges with biomimetic patterning technologies are reproducibility, slow processes, and high cost.

Surface modifications for biomimetic materials

Extensive research has been done to modify the surface of materials to elicit specific biological responses and reliably direct new tissue formation. Immobilization of natural materials onto a surface is the most common method, but coatings created by soaking 3D materials in aqueous solutions also create biologically relevant porous and crystalline layers.

Interestingly, research into creating biomimetic materials for bone has lead to the study of how turban snails create their shells. The shells are created by assembling inorganic minerals from the surrounding water onto layers of proteins. Recreating this approach with collagen or silk produces bone-like scaffolds that could be used for tissue engineering or regenerative medicine. This approach, however, comes very close to using natural scaffolds outright, rather than being able to label this as merely biomimetic.

Trends in articular cartilage repair

The authors also discuss slight modifications to microfracture and cell transplant techniques in clinical use for articular cartilage repair. The same shortcomings have already been discussed in a previous paper. While the authors suggest that these shortcomings call for a biomimetic solution, none are mentioned or suggested.

Biomimetic materials are hard work

Making a synthetic material biomimetic is not as easy as once thought. Large hurdles stand in the way of synthesizing a material that produces the desired biological response in a medical context. The use of natural polymers removes many of these hurdles.

The problems found in 3D printing of syntheic hydrogels have largely been overcome, and are in commercial use, by companies like Organovo. Their process cannot yet replace complex organs, but 3D tissues and simple blood vessels are being made today using natural scaffolds.

Natural materials already have relevant micro and nano patterning that aids in healing in many different contexts. That diatoms and other plants are being used as templates suggests that diatoms and other plants should be used themselves.

The most promising research noted in this paper for biomimetic surface modifications is actually an example of natural scaffolds research. Widespread commercial success has been found using surface modifications in bone repair. However, these are mainly modified metal surfaces, such as joint replacement devices and orthopedic screws, that are modified to better integrate with surrounding bone.

Tissue engineering and regenerative medicine literature has undergone a major shift in focus over the last 10 years. Where once synthetic polymers and clever chemistry dominated the pathway to commercialization, natural polymer research has taken hold and eclipsed the synthetic promise of creating new tissue and regenerating injuries. This shift is highlighted by this review on biomimetic challenges.

  1. Cen Chen, Sumi Bang, Younghak Cho, Sahnghoon Lee, Inseop Lee, ShengMin Zhang, Insup Noh. “Research trends in biomimetic medical materials for tissue engineering: 3D bioprinting, surface modification, nano/micro-technology and clinical aspects in tussie engineering of cartilage and bone.” Biomaterials Research 20 (2016), 10.
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