Regenerative medicine is a multidisciplinary field that deploys biologists, engineers (biomedical, mechanical, electrical), and medical personnel (surgeons, cardiologists, research nurses) to work together.
Regeneration means the regrowth of a damaged or missing organ part from the remaining tissue. As adults, humans can automatically regenerate some organs, such as the liver – if part of the liver is lost by disease or injury, the liver grows back to its original size, though not its original shape. And our skin is constantly being renewed and repaired. Unfortunately, many other human tissues don’t regenerate, and the goal in regenerative medicine is to find ways to kick-start tissue regeneration in the body, or to engineer replacement tissues.
Research has pursued a variety of ventures, including building new bioreactors, finding ways to grow billions of necessary cells, discovering how to derive stem cells from an adult individual, and the advent of new materials that can be used as templates, or “scaffolds,” to guide the growth of new tissue.
Typically, three individual groups of biomaterials—ceramics, synthetic polymers and natural polymers—are used in the fabrication of scaffolds for tissue engineering. Each of these individual biomaterial groups has specific advantages and disadvantages so the use of composite scaffolds comprised of different phases is becoming increasingly common.
Biomaterial scaffold requirements
Numerous scaffolds produced from a variety of biomaterials and manufactured via a plethora of fabrication techniques have been used in the field in attempts to regenerate different tissues and organs in the body. Regardless of the tissue type, a number of key considerations are important when designing or determining the suitability of a scaffold for use in tissue engineering:
- Biocompatibility: after implantation, the scaffold or tissue engineered construct must elicit a negligible immune reaction to prevent it causing from such a response that might reduce healing or cause rejection by the body.
- Biodegradability: the objective of tissue engineering is to allow the body’s own cells, over time, to eventually replace the implanted scaffold or tissue engineered construct.
- Mechanical properties: ideally, the scaffold should have mechanical properties consistent with the anatomical site into which it is to be implanted and, from a practical perspective, it must be strong enough to allow surgical handling during implantation.
- Scaffold architecture: scaffolds should have an interconnected pore structure and high porosity to ensure cellular penetration and adequate diffusion of nutrients to cells within the construct and to the extra-cellular matrix formed by these cells.
The ability of polymers to span wide ranges of mechanical properties and morph into desired shapes makes them attractive for scaffolds, self-assembling materials, and nanomedicines.
Numerous synthetic polymers have been used in the attempt to produce scaffolds including polystyrene, poly-l-lactic acid (PLLA), polyglycolic acid (PGA) and poly-dl-lactic-co-glycolic acid (PLGA). While these materials have shown much success, as they can be fabricated with a tailored architecture, and their degradation characteristics controlled, they have drawbacks including the risk of rejection due to reduced bioactivity. Concerns exist about the degradation process of PLLA and PGA as they degrade by hydrolysis.
Biological materials such as collagen, various proteoglycans, alginate-based substrates and chitosan have all been used in the production of scaffolds for tissue engineering. Unlike synthetic polymer-based scaffolds, natural polymers are biologically active and typically promote excellent cell adhesion and growth. Furthermore, they are also biodegradable. However, fabricating scaffolds from biological materials with homogeneous and reproducible structures presents a further challenge. In addition, the scaffolds generally have poor mechanical properties.
Electrospinning
The electrospinning process, although still being optimised for many different applications, is no longer a university laboratory curiosity. It is now established as a commercially viable manufacturing process with nanofibres of a range of different polymers.
Creating composite structures using nanofibres can be considered in two ways. Firstly, nanofibres can be incorporated in, for example, a thermoplastic matrix to enhance strength, stiffness, wear resistance and a reduced risk of crack propagation in relatively weak materials. Secondly, a strength-yielding fibre can be co-spun using an electrospinning process such that alignment of the nanotubes in the fibre is achieved, leading to enhanced performance of the fibre combination.
Initial applications for electrospun nanofibres in the medical field include 3D scaffolds, which provide an ideal substrate for the growth of human cells resulting in major advantages over cells grown in a 2D network.
In order for the pharmaceutical industry to take full advantage of the potential of 3D scaffolds, the process must be compatible with automated testing and imaging systems. The Electrospinning Company has solved this problem with its new Mimetix scaffold. This is laser-welded into the base of a 96-well plate, providing a flat base for imaging and excellent well-to-well uniformity.
Oxford Biomaterials has been developing novel product forms based on silk nanofibres since 2001. The focus has been on the development and modification of spider silk-like fibres and scaffolds for the medical device industry.
Although scaffolds for supporting cell growth have been of much interest for many years in the context of regenerative medicine, there have been concerns about the potential for poor cell infiltration throughout the entire depth of the scaffolds. Such problems have limited the use of scaffolds as tissue engineering biomaterials in regenerative medicine.
Researchers at University College London (UCL) have been able to demonstrate the ability to electrospin cells directly with both a biopolymer and other advanced materials for simultaneously forming a 3D living system that imitates native tissues.
Spi3Dr Ltd is an early stage startup company founded by Dr Anthony Cooper with ambitions to revolutionise 3D printing through the improvement of the materials that can be 3D printed. It is developing a process to produce 3D printed composites containing an appropriate nanofibre reinforcing polymer.
While the industrial 3D printer is capable of producing highly complex structures based on thermoplastics or thermosets, at the low-cost end of 3D printing equipment, only thermoplastics can be used. Incorporation of nanofibres at the 3D printer print head provides an attractive proposition, with the ability to switch the nanofibres on and off, leading to the potential for patterning at differing nanofibre densities and fibre types. Work continues with a method of electrospinning carbon nanotubes (CNTs) into a polymer delivered via a 3D printer.
Novel composite nanofibres have also been produced at University of Manchester. In this case, the nanofibres are co-electrospun with an outer sheath covering a central core. While the shell material can be a conventional electrospun polymer, such as PCL, the core may be a material such as PEO, olive oil, mineral oil or sugar water solution and may be removed after co-electrospinning, leaving a novel hollow fibre construction. Applications for such constructions are being developed given the range of material combinations that might be possible.
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Further Reading:
- Wireless thermometer patch taps into feverish wearables market
- Color It Medical – Colored Thermoplastic Compounds for Medical Applications
- K Show Recap: Medical Polymers in the Spotlight
References:
- Fergal J.O’Brien Biomaterials & scaffolds for tissue engineering. Materials Today Volume 14, Issue 3, March 2011, Pages 88-95 https://doi.org/10.1016/S1369-7021(11)70058-X
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Very interesting post. Do you think stem cells therapy effective for heart muscles tissues?