Recent & potential biomaterials

Biomaterials act as scaffolds for tissue engineering and promote the process of formation of new tissues & organ regeneration. Also leads to improved quality & function of the regenerated tissues. This multi-disciplinary approach using nature biology, engineering techniques & clinical sciences is so very important for man and animals.

Bioscaffold is defined as:

A naturally derived or artificial structure, implanted in the body, on which tissue grows in the form of a missing or damaged organ etc.; the process being called tissue engineering.

{what remains is the use of bioscaffolds as drug delivery systems}

Tissue engineering builds an interface between biomaterials & biocompatibility & integrate cells, natural or synthetic scaffolds allowing specific signals to create new cells.

{the electrical signals can also be effected due to conduction properties of some biomaterials.}

People also ask ?

Scaffolds & NanoMaterials:

  • Incorporating nanomaterials enhances the quality & function of regenerated tissues.

  • nano materials possess biomimetic abilities & appropriate physicochemical properties. Nanomaterials improve adhesion, and proliferation & allow cell differentiation leading to tissue regeneration.

  • In craniofacial tissue engineering, natural and synthetic polymers, ceramics, composite materials & electrospun nanofibers are used.

  • In bone/cartilage tissue engineering, synthetic & natural polymers are used to due their biodegradability & ease of fabrication.

Some Bone Forming Materials & Nanoceramics:

  • Some materials for excellent bone formation include nanofibres synthetic and natural polymer scaffolds of electrospun polycaprolactone, poly(lactic-co-glycolic acid)(plga), polyvinyl alcohol, collagen etc.

  • nanoceramicsare known to be useful as bone substitutes, coatings & fillers due to their dimensional similarity to bone/cartilage tissue and unique surface properties, like surface topography, large surface area, surface chemistry, surface wettability & surface energy.

Hydroxyapatite (HAP) & Nano Hydroxyapatite (NHAP)

  • Osteoblast adhesion & function. Nhap also improves cell attachment  & mineralization. Thus nhap is used clinically due to its bioactivity.
  • other nano sized ceramics materials include alumina, zinc oxide & titania which increase osteoblast adhesion significantly.
  • nhap with collagen or chitosan scaffolds are immensely important for bone repair. These hydrogels swell in aqueous medium & permit transport of enzymes & nutrients to & fro of the supporting ceramic scaffolds. Addition of nano copper or zinc allows increased swelling & only some anti-bacterial activity.

BIOCERAMICS:

  • Bioceramics are synthetic, crystalline, inorganic material.
  • Bioglass are synthetic, amorphous, inorganic materials
  • Bioceramics have been used for past 5 decades due to their biocompatibility, excellent osteo-conductive & osteo-inductive properties and have mineral composition similar to that of human bone.

       These include all calcium phosphates with a different Ca/P molar ratios.

      Some examples:

Substance

Ca/P ratio

Properties

Amorphous Calcium Phosphate

1.2-2.2

 –

α – TCP

1.5

Quickly resorbed

β -TCP

1.5

Slowly resorbed

HAP

1.67

Not resorbed unless in Nano form

Other examples:

Calcium silicates – Tricalcium silicates

Bioactive Glass – silicate; borate; boron-silicate; phosphate; metal doped

Bioactive Glass Ceramics – are partially crystallized materials – ZrO2 doped calcium silicate

Mechanism:

HAP allows partial dissolution of Ca & phosphate ions in aqueous medium. Carbonates precipitate the Ca & this allows formation of a carbonated apatite layer. This layer acts as a substrate, allowing growth & differentiation of osteoblasts. The bioactivity can be improved by replacing phosphate ions with carbonate or silicate ions. 

When nHAP is doped with Magnesium in its microstructure, during its synthesis, a superior anti-bacterial material is obtained. Enhanced anti-bacterial activity is observed of strontium or ceric ions are introduced in the microstructure of nHAP. However, Zinc ions did not exhibit good antibacterial effect.

HAP can be loaded with vancomycin or peppermint oil for control of infections of tooth.

 

HAP based Additive Manufacture Materials

Scaffolds of neat HAP by 3D printing is difficult due to lack of bonding & flow ability while printing. Thus it also requires additives like sacrificial materials (polymeric binders; poly vinyl butyral; polyacrylamide) or ceramics or bioactive glass.

Binders also include Sodium alginate & maltodextrins, PVA.

HAP + Other Inorganic materials

Incorporation of following materials improve bioactivity, mechanical properties, osteoconductivity & osteogenicity.

  • HAP (15%) with β-TCP (85%) can be made using robocasting. These 2 can also be combined with Calcium sulfate for better 3D prints of solid substrates simply using any water-soluble binder.
  • HAP with Calcium Silicate or Calcium sulfate

HAP with Natural Polymeric materials

These have been developed due to lower mechanical property & poor flexibility of pure HAP constructs.

HAP+ Collagen

HAP+Silk

HAP+Chitosan+Dextran Sulfate

 

HAP with Synthetic Polymers

HAP + Poly (L-lactide) (PLA)

HAP + Poly (lactide-co-glycolide) (PLGA)

Hap + Poly (ε-caprolactone) (PCL)

HAP + Poly (propylene fumarate) (PPF)

Carbonated HAP + PLA

 

HAP with Natural & Synthetic Polymers

These tri-composite materials have scarce literature and are a subject of investigation.

HAP + gelatinized corn starch + PCL has been studied.

HAP with Other components

HAP+PCL composites have been coated onto bioactive glass.

3D printed scaffolds of 60%HAP+20%β-TCP were produced by robocasting and these were then coated with Calcium peroxide in PCL matrix. This allows release of oxygen at the tissue site promoting its growth.

 PLGA+ β-TCP scaffolds were coated with HAP

 HAP+Gelatin+Chitosan+CMC scaffolds were made using 3D printing.

3D printed constructs of HAP microspheres with Graphene showed good microstructural, mechanical & electrical conductivity.However, what needs investigative efforts is the composites made using our highly characterized materials:Reduced Graphene Oxide, (AIRGO), Graphene Oxide (AIGO)

Triple layer scaffolds have been made:

 Top layer – Methacrylated gelatin

   Middle layer – HAP (3%) + Methacrylated gelatin (20%)

   Bottom layer – HAP (3%) + Methacrylated gelatin (30%)

 Silicon doped HAP + Gelatin scaffolds

Strontium doped HAP + PCL scaffolds

Magnesium doped HAP + PCL scaffolds

HAP + PCL with CNTs scaffolds showed highly porous network enabling good bioactivity, mechanical strength & electrical conductivity

       USE OF HAP IN DRUG DELIVERY : 

  • Low temperature 3D printing of HAP scaffolds allows loading of drugs for therapeutic benefits. HAP is a promising biomaterial for not only bone tissue regeneration but also drug delivery.
  • Doped Hap or Magnetically susceptible HAP can be made & have been investigated for drug delivery.
  • Delivery with HAP is not only drugs like Gentamycin (antibiotic); Cisplatin (anti-cancer); Carvedilol (anti-hypertensive) but also molecules like DNA, RNA & proteins is possible.
  • As the method of 3D printing is highly controllable and precise one can expect to make controlled release drug delivery systems using HAP.
  • Thus HAP based BIOINKS of different formulations can be used to produce desired characteristic scaffolds.
  •  If in the 3 dimensions of space are well known but if we were to listen to physics….one should include a 4th dimension i.e. Time … then we could have a programmable scaffold material which would function in a desired manner over a period of defined time. Materials like NITINOL are elastic and exhibit memory effect & also ternary metal systems of NITINOL with 9%Cu need to be explored along with HAP.
  •  To add more to the complexity, consider making these scaffolds in a complex curvature patterns and not straight forward squares or disks.
  • As mentioned before MWCNTs, Fullerenes have an un-explored potential in making HAP scaffolds.
    A Schwarzite is another material for using in 3D printing of HAP scaffolds.
  • Schwarzite have a three-dimensional sp2 carbon structure with negative Gaussian curvatures.