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MAT3430 > Biological materials as biomaterials > Flashcards

Biological materials as biomaterials Flashcards

1
Q

What is a biological material?

A

a substance that is produced by an organism during its life

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2
Q

What is a biomaterial?

A

a biological or synthetic substance which can be introduced into body tissue as part of an implanted medical device or used to replace an organ, bodily function, etc

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3
Q

What are the uses of biological materials?

A

From graft or transplant of the material, slightly altered to…
• retain their complex structure but completely changing the chemistry to
• retain the chemical properties but completely reorganising the structure

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4
Q

What are the clinical applications of biological materials?

A
  • Simplest – keep the structure transplant it (graft)
  • Inject it - fillers
  • Implant it - fillers
  • Fibres – sutures
  • Gels for controlled drug release
  • Wound dressings – single material, or composites
  • Tissue engineering scaffolds – single materials or composites
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5
Q

What percentage of the total body is collagen?

A

20-30%

Half of total body collagen is in the skin

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6
Q

Where is type 1 collagen found?

A

90% us Type I (fibrillar) found in bone, skin, ligaments, cornea, organs

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7
Q

What percentage of skin is collagen?

A

70%

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8
Q

What is the structure of collagen?

A

3 polypeptide chains each ~1000 amino acids long
• Each polypeptide contains repeats of Gly-X-Y. (Glycine and 2 amino acids usually proline or hydroxyproline). Repeats are akin to monomers in polymer (previous lecture).
• Gly is key as it enables the three chains to wind round each other in alpha helix to make a procollagen molecule
• In some collagens called fibrillar collagens (e.g type I) the procollagens stack up into fibrils

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9
Q

How can collagen by used as a biomaterial?

A
  • Skin and tendon collagen from animals can be solubilised and made into different forms
  • Sponges, sheets, pellets
  • Used as skin substitutes, filler materials and for drug deliver
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10
Q

What is the issue of extracting collagen from animals?

A
  • Vast majority Bovine derived
  • But EU regulatory issues coming in
  • Other solutions: Jellagen
  • Preserved triple helix structure and function
  • > 90% pure
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11
Q

How is collagen synthesised to avoid extracting from animals?

A
  • Recombinant human protein
  • Overcomes any immune problems with animal collagen
  • Insert the gene into another cell animal/bacteria/plant
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12
Q

What is an autograft?

A

A patient’s tissue replaces same tissue elsewhere
• E.g. Collagen: skin graft from one part of body to another
• E.g. Collagen: Ligament from patella used to repair anterior cruciate ligament (ACL)

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13
Q

What is an allograft?

A

Tissue from donor and used in patient for same function
• E.g. Collagen: Skin graft from one person to another to other
• E.g. Collagen: Tendon graft, e.g using donor Achilles tendon for ACL

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14
Q

What is a xenograft?

A

Tissue taken from animal used for same function in human

• E.g. Collagen: porcine and bovine heart valve

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15
Q

What are the advantages of xenografts?

A
  • Reduced rate of thromboembolism
  • Freedom from anticoagulant related haemorrhage
  • No immunosuppresive therapy needed
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16
Q

What are the disadvantages of xenografts?

A
  • Disappointing long term performance
  • Degradation caused by calcification and tearing of leaflets.
  • Stress concentration leading to degeneration
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17
Q

How are acellular collagen membranes used as wound dressings?

A

E.G Perma coll
Permacol™ surgical implant is a sterile off white, moist, tough but flexible flat sheet of acellular porcine collagen and its constituent elastin fibres presented moist in sterile saline. Permacol™ surgical implant comes ready to use in double vacuum packed aluminium foil/polyethylene sachets which are impermeable to oxygen, and is sterilised by gamma irradiation.

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18
Q

What are the types of temporary membrane skin grafts?

A

1) Porcine xenograft
- Adheres to coagulum, excellent pain control
2) Biobrane
- Bilaminate, fibrovascular ingrowth into inner layer
3) Split thickness allograft
- Vascularizes and provides durable temporary closure
4) Various semipermeable membranes
- Provides vapor and bacterial barrier
5) Various hydrocolloid dressings
- Provides vapor and bacterial barrier, absorbs exudate
6) Various Impregnated gauzes
- Provide barrier while allowing drainage
7) Allogenic dressings
- Provides temporary cover while supplementing growth factors

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19
Q

What are the types of permanent membrane skin grafts?

A

!) Epicel

  • Provides autologous epithelial layer
    2) Integra
  • Provides scaffold for neodermis, requires delayed thin autograft grafting
    3) AlloDerm
  • Consists of cell-free human dermal scaffold, requires immediate thn autograft
20
Q

How is collagen used for sutures?

A

1) ‘Catgut’
• Really bovine, sheep or goat intestine! Cleaned, split into ribbons, cross linked and polished.
• Advantage absorbable, inexpensive
• Disadvantage, weak points, fraying

2) Bovine tendon
• Tendon is digested to make gel then extruded to make fibres, more consistent than cat gut

21
Q

How are natural materials used as a scaffold for cells and growth factors?

A

Collagen gel for ACL repair
Murray envisions a simple outpatient procedure for repairing ACL tears: injection of a collagen gel, mixed with the patient’s own platelets and plasma, via a small knee incision.

22
Q

What are the uses of collagen?

A

1) Sutures: Extruded tape
2) Hemostatic agents: Powder, sponge, fleece
3) Blood vessels: Extruded collagen tube, processed human or animal blood vessel
4) Heart valves: Processed porcine heart valve
5) Tendon, ligaments: Processed tendon
6) Burn treatment: (dermal regeneration)
Porous collagen-glycosaminoglycan (GAG) copolymers
7) Peripheral nerve regeneration: Porous collagen-GAG copolymers
8) Meniscus regeneration: Porous collagen-GAG copolymers
9) Skin regeneration (plastic surgery) :Porous collagen-GAG copolymers
10) Intradermal augmentation: Injectable suspension of collagen particles
11) Gynecological applications: Sponges
12) Drug delivery systems

23
Q

What are the advantages of collagen?

A
  • Available in abundance and easily purified from living organisms (constitutes more than 30% of vertebrate tissues);
  • Non-antigenic;
  • Biodegradable and bioresorbable;
  • Non-toxic and biocompatible;
  • Synergic with bioactive components;
  • Hemostatic — promotes blood coagulation;
  • Formulated in a number of different forms;
  • Biodegradability can be regulated by cross-linking;
  • Easily modifiable to produce materials as desired by utilizing its functional groups;
  • Compatible with synthetic polymers
24
Q

What are the disadvantages of collagen?

A
  • High cost of pure type I collagen;
  • Source is subject to further regulations if vertebrate derived (prions)
  • Variability of isolated collagen (e.g. crosslink density, fiber size, trace impurities, etc.);
  • Hydrophilicity which leads to swelling and more rapid release;
  • Variability in enzymatic degradation rate as compared with hydrolytic degradation;
  • Complex handling properties;
  • Side effects, such as bovine spongeform encephalopathy (BSE) and mineralization
25
Q

How can collagen be processed into Gelatin?

A
  • Denaturing collagen by heat or pH = gelatin
  • No triple Helices, randomly coiled
  • Breaks down easily in the body
  • Tangled fibres absorb water, creates gel
26
Q

What are GAGs?

A

repeating disaccharide (sugar) units that attach to a core protein to make a proteoglycan

27
Q

What is hyaluorinic acid?

A

Largest GAGS: n-acetylyglucosamine and glucuronic acid repeats
• Hyaluronic acid attracts water, good for gels
• Can be esterified and cross-linked to make more viscous for sponges and fibres

28
Q

Where are GAGS extracted from?

A
  • Chicken (rooster combs)
  • Bovine vitreous fluid
  • Sharks
  • Bacterial fermentation
29
Q

What are hyaluronic acid GAGS used for?

A
  • Mostly as injections
  • Joint lubrication/ synovial fluid
  • Improve Bladder lining
  • Skin injections (as for collagen)
  • As film
  • Eye surgery
  • As scaffold
30
Q

What is alginate?

A
  • Polysaccharide co-polymers
  • Extracted from seaweed
  • Ratio of G:M depends on seaweed type
  • Forms gel in presence of divalent ions such as Ca+
  • Biocompatible but biodegradability uncertain
31
Q

What is the current use of alginate and why?

A
  • Good absorption, stays moist, don’t inhibit contraction
  • But can dry out wound, need additional dressing
  • Also seeing more use as cell encapsulation for injectables
32
Q

What is Chitin?

A

polysaccharide (sugar) found in crustacean exoskeletons

- Co-polymer of N-acetyl-glucosamine and N-glucosamine units randomly or block distributed

33
Q

What is Chitosan?

A

deacylated chitin, determined when >50% N-glucosamine units are deacylated, but the upper limit varies
- soluble at pH below 6, can form gel, hence preferred material to work with
• Films and fibres can be formed using cross-linking
• Cationic

34
Q

How is chitosan extracted?

A

Decalcification (dil. aq HCL soln) -> Deproteination (dil. aq NaOH soln) -> Decolourisation (in 0.5% KMnO aq and Oxalic acid aq or sunshine)
= chitin
->Deacetylation (in hot conc NaOH soln)
=chitosan

35
Q

What are the multiple applications of chitosan?

A
  • Has good wound healing, absorption and antibacterial properties
  • Bandages (electrospinning)
  • Control of blood cholestrol
  • Burns wound dressings
  • Contact lenses
  • Drug delivery
  • Weight loss, apparently chitosan absorbs fat!
36
Q

What is bone?

A

Defatted, deprotinated (Sodium hydroxide, hydrazine, heat)

37
Q

What is endobon?

A

osteoconductive hydroxyapatite ceramic (HA ceramic) which is particularly suitable for the use as a bone graft substitute. Endobon® is of biological origin (bovine spongiosa).

38
Q

What is bio-oss?

A

osseointegrated with newly formed bone.

The clear decalcification seams on the surface of Bio-Oss® indicate resorption by the adjacent osteoclasts

39
Q

Why is calcium carbonate not a good biomaterial?

A

It has a high dissolution rate

40
Q

How is calcium carbonate converted to hydroxyapatite?

A
  • using hydrothermal process
    Comercially available as ‘coralline hydroxyapatite’
    Properties can be further improved by coating
41
Q

What is poly hydroxyalkanoates (PHA)?

A
  • Polymers (linear polyesters) synthesised by bacteria
  • More than 150 monomers, very diverse set of materials
  • Most simple is PHB, poly(3-hydroxybutarate)
42
Q

How is collagen synthesised?

A

1) synthesis of pro-alpha chain
2) hydroxylation of selection prolines and lysines
3) glycosylation of selected hydroxylysines
4) self assemble of three pro-alpha-chains
5) procollagen triple helix formation
6) secretion
7) cleavage of propeptides
8) self assembly into fibril
9) aggregation of collagen fibrils to form a collagen fibre

43
Q

What are the applications of Endobon?

A

the permanent filling and reconstruction of aseptic bone defects in trauma surgery and orthopaedics. Thus, bone defects after fractures, TJR, bone cysts, arthrodeses and benign bone tumours can ideally be filled with Endobon

44
Q

Why is calcium carbonate converted to hydroxyapatite?

A

1) pro osteon’s interconnected porous structure closely resembles the porosity of human cancellous or cortical bone
2) implant provides a strong natural foundation for new bone growth
3) implant offers structural support during the healing pocess
4) upon healing, the composite of bone and pro osteon is comparable in strength to the surrounding bone
5) naturally biocompatible
6) healing rates equivalent to patient’s own bone
7) eliminates risk of immune response and disease transmission

45
Q

What is poly hydroxyalkanoates (PHA) used for and why?

A

Used in sutures, artificial skin, drug delivery, implant materials
• Long degradation times
• Good biocompatibility

MAT3430 (12 decks)

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