Bioactive scaffolds

Question 1

Why is bone so important to replace? And why is it so hard?

Answer 1

• • Bone is a highly vital organ with many functions – supports muscle, protect internal organs, regulates blood formation and in calcium homeostasis.
• • Great importance due to high bone transplantation, for complete bone dissemination and other large fractures.
• • Bone is the second most transplanted tissue to blood – great need.
• -However bone has a very complex structure –>Bone is a composite of collagen (the polymer) and the mineral HCA which is difficult to imitate. It has a dense and yet porous structure.
• -We also have to consider the blood vessels that feed bone when trying to regenerate as without they won’t survive.

Question 2

Outline the process of bone regeneration.

Answer 2

• • Bone is easier to mimic than cartilage – the porous structure can be mimicked in a scaffold which is implanted, which should attract the mesenchymal stem cells from blood and attach to the scaffold.
• • The mesenchymal cells will then start to become bone like cells - osteoblasts, produce bone matrix at site of newly forming bone which induces calcification.
• • Haematopietic stem cells are also attracted and they form osteoclasts
• • Osteoblasts and osteoclasts will remodel the partically calcified tissue into woven bone
• • Blood vessels also should form to prevent the bone cells from dying
• • Eventually the scaffold should degrade, leaving regenerated bone.

Question 3

What are the criteria of the ideal scaffold?

Answer 3

• • Should act as a temporary template for tissue growth – some kind of porous structure large enough for cells to go through (bone ingrowth) and allow vascularisation.
• • Shouldn’t form fibrous capsules– which can be caused by inert biomaterials. To avoid this, it has to be a bioactive material.
• • Biocompatible – not toxic and shouldn’t be immuno-rejected.
• • Osteoconductive and Osteoinductive.
• • Should bind to the host tissue without formation of scar tissue.
• • Similar mechanical properties to the host tissue. If the graft differs in its Young’s modulus (i.e. higher than native bone), it will lead to implant stress-shielding and failure.
• • Resorb at same rate as tissue repairing at a controlled rate - safely, without producing toxic materials.
• • Needs to meet FDA/ISO/CE standards.

Question 4

What are the two options for bone scaffolds? And why are bioceramics preferred?

Answer 4

• • There are two options for the sources  autologous derivation (e.g. from humans or from cows, or pigs – where the mineral part w/o organic compounds is used) or artificial, the most common being bioceramics.
• • Artificial bone graft materials are needed that regenerate bone defects without the need for graft operations.
• • Synthetic biomaterials allow control over the surface chemistry, degradation rate and structure. Bioceramics are preferred as they are bioactive,

Question 5

Describe features of the bioceramic coralline HA.

Answer 5

• -It is derived from naturally occurring coral
• • Natural coral is 97% calcium carbonate, which can be converted to HA by hydrothermal conversion in presence of ammonium phosphate.
• • The structure formed will be highly porous, similar to bone structure.
• • The material slowly resorbs, is osteoconductive but has lower compressive strength than normal bone. Coral is also hard to obtain.

Question 6

Describe features of the bioceramic actifuse.

Answer 6

• • It is a silicon substituted calcium phosphate.
• • Current market leader - mainly used in spinal fusion fractures.
• • The silicon in the HA will make the graft more bioactive and stimulating to bone growth as it produces a more porous structure. Actifuse consists of only 0.8% silicon.
• • Foaming process is used in its generation.
• • It does mimic porous bone
• • Its low fracture strength means that it cannot be used in load bearing applications.

Question 7

Describe the process of selective laser sintering for additive manufacturing of scaffolds.

Answer 7

Selective laser sintering (SLS) is a layer by layer technique.

• • An additive manufacturing technique used for production of prototype models and functional components.
• • Uses lasers to sinter powdered material, binding it together to create a solid structure.
• • Sintering is a process involving applying heat to cause powders to diffuse (fuse) together to form a solid, often used for making ceramic objects.
• • It can be used to make scaffolds – the laser will fuse particles into a 3d mass layer by layer.
• • Allows you total control of the microstructure and can generate nanocomposite scaffolds.

Question 8

Describe the features of bioactive glass.

Answer 8

• • It is arguably the most bioactive material
• • A glass formulation with less silicon and higher calcium levels than conventional glass.
• -The first material to be developed that could bind to bone. It bound so strongly that it couldn’t be removed..
• • Forms layer of hydroxyapatite in body – similar to natural form of bone.
• • Stimulates more bone synthesis (osteogenesis) than synthetic HA – its dissolved silica stimulated bone to regenerate.
• • There isn’t a similar product that has porous structure. However it’s only commercially available as a powder - £1000 per sachet.
• • Very popular in sensitive toothpastes – e.g. sensodyne repair. When teeth are brushed with bioactive glass, the calcium carbonate will cause remineralisation of the dentine tubules.

Question 9

What is purpose of sol-gel technique in regards to bioactive glass?

Answer 9

• • Porous bioglass scaffolds have been difficult to produce because it will crystallize on sintering.
• • Sol-gel foam technique avoids this problem.
• • They have a hierarchical pore structure comprising interconnected macropores, with interconnect diameters in excess of the 100 mm that is thought to be needed for vascularized bone ingrowth, and an inherent nanoporosity of interconnected mesopores (2-50 nm) which is beneficial for the attachment of osteoprogenitor cells.
• -They also have a compressive strength in the range of cancellous bone

Question 10

Describe the sol-gel process and the foaming alteration.

Answer 10

• • Called ‘sol-gel’ as you start off with a solution and finish off with a gel.
• -The process involves hydrolysis of silicate precursors to generate a solution.
• -The sol will then undergo condensation to form nanoscale particles which will aggregate together during gelation.
• • It is then heated so the nanoscale particles will fuse together, with inherent nanoscale porousity.
• • The sol gel scaffolds have structure that mimics bone and allows it to act as a template for bone cells to attach to and aid regeneration.
• • However they are brittle.

A foaming step is added to the technique to produce a porous scaffold.
The hydrolysed sol can be foamed by vigorous agitation in air with theaid of a surfactant. The surfactant lowers the surface tension stabilise the air bubbles formed to produce a porous scaffold.

Question 11

Describe the features of conventional composites for bone scaffolds.

Answer 11

• • Composite scaffolds have been generated by incorporating bioactive glass particles into biodegradable polymers, such as PLA.
• • However this leads to problems as the glass is covered by polymer so they do not come into contact with bone and since polymers degrade rapidly (whoosh effect), it causes the scaffold to rapidly lose mechanical strength.
• • The only way to overcome this is to create a nanocomposite or hybrid –>
• • Nanocomposites aim to allow the bioactive inorganic and organic phases to interact with bone, creating a tough material. They will also degrade in a more linear fashion than conventional polymers.

Question 12

Describe the features of hybrids for bone scaffolds.

Answer 12

• • They are form of nanocomposite, where inorganic (e.g. silica) and organic phases (e.g. polymer) are covalently bound together.
• • Have greatest potential for combining desire properties for bone regeneration.
• • Consists of interpenetrating networks of different polymers. The chains are interlocking at the nanoscale which gives unique mechanical properties and makes sure they degrade as one compound.
• • e.g. silicon 40 / 60 gelatin foam –> formed by sol gel technique.
• –> Qualities can be easily tailiored depending on function - changing the amounts of silica and gelatin will alter the toughness and bioactivity. T
• –> hey are flexible and have same young’s modulus as bone.
• –> Gelatin was chosen as it is hydrolysed form of collagen
• –> A problem is that these materials are new and complicated so going through regulatory procedures are very expensive and time consuming, meaning that it will be a long time before they enter clinical trials.