18) Synthetic vascular grafts are man-made tubes which replace or bypass part of a

blood vessel, most commonly an artery. They work in a similar way to natural
blood vessels. They provide a tubular bypass for arteries that have become
narrow or blocked due to disease processes.
a) Describe characteristics or requirements for the ideal vascular graft.

 It must be durable, withstanding after implantation the dual threats of

biodegradation and mechanical fatigue.
 The ideal graft should have and maintain the same compliance as a normal artery:
It should be flexible, maintaining its contour and have kinking resistance, bending
without partial occlusion–as it crosses joints.
 The graft must not harm the host in anyway.
 Its luminal surface must interact with blood elements in a minimally traumatic,
nonthrombogenic fashion.
 It should be resistant to infection.
 It must be capable of sterilization without graft alteration. The ideal graft should
have an optimal porosity, allowing for good incorporation without causing
unmanagable bleeding following implantation.
 The handling point of view, it must be readily available in multiple lengths and
sizes, and its handling characteristics should include an ease of suturing and
maintenance of integrity.

b) What are three major materials used to make synthetic vascular grafts?
1. Dacron or Polyethylene Terephthalate (PET)
2. Expanded Polytetrafluoroethylene (ePTFE)
3. Polyurethanes

c) Would you prefer to use them for large or small diameter vascular grafts? Explain
why?
• These materials work well for large diameter vascular grafts (>5-6 mm) but have
low long-term potency for small diameter grafts (4 mm).
• In large diameter synthetic vascular grafts the accumulation of fibrous and cellular
material is not great enough to cause the graft to shrink in diameter significantly.
• In small diameter synthetic vascular grafts the accumulation of material is often
significant enough to cause the blood vessel to become occluded.

d) What are the benefits and disadvantageous of the materials described in b?

 This is a fluorocarbon polymer, formed into sheets by a paste extrusion process,

producing a porous material that has solid nodes interconnected by fine fibrils.
 Its smooth surface is less thrombogenic than Dacron.
 Its smooth wall is prone to kinking as it passes around joints necessitating it to be
externally supported.
 It can be used in conjunction with vein as a composite graft.
 The PTFE grafts in clinical use are impervious to blood, resistant to dilatation,
and are chemically inert, highly electronegative and highly hydrophobic.
  The grafts are available in different wall thicknesses.
 Thinner wall have easier handling characteristics, better conformability and
improved compliance.

e) What are benefits of using collagen as a material for synthetic vascular grafts?
How would you increase the mechanical strength of collagen vascular grafts?
Why incorporate heparin in collagen vascular grafts?

 It is biodegradable and has good mechanical properties.

 Since collagen is biodegradable, as the device degrades tissue can grow into the
device.
 This is advantageous because ideally as the collagen implant degrades the newly
formed tissue will replace it, which results in a gradual transfer of stress from the
implanted device to the newly formed tissue.

How collagen helps to improve Graft material

 Collagen can be crosslinked to form a polymer with sufficient mechanical
strength to resist the collapse of the blood vessel.
 Collagen can be crosslinked with gluteraldehyde or N-(3-dimethyaminopropyl)-
N’-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS).
 Gluteraldehyde can often cause an immune response because of the cytotoxicity
of the degradation products.
 On the other hand, EDC and NHS can be removed from the collagen more
completely and do not cause and immune response.
 Heparin is a negatively charged anti-thrombogenic protein that can be
incorporated into collagen, which is inherently thrombogenic.
 The incorporation of heparin significantly reduces the thrombogenic properties of
collagen and at allows it to be used as a material for vascular implants.

17) Post Surgery anti-adhesion

a) What are post-surgical adhesions, what causes them to form, in what types of
surgery are they most often formed?

 Abnormal bands of tissue that connect anatomic sites at locations where there
should not be connections.
 The attachment of internal organs which spouse to be free.
 Post-operative surgical adhesions are formed as a result of trauma or injury to
tissue such as the surgical incision made into the abdominal wall.
 it is caused by prior surgery, infection and other inflammatory process
(endometriosis)
 It is mostly common in both tissues and organs of the human body.
 Commonly formed in surgery such cholecystectomies, appendectomies, colon
surgery and pelvic surgery.
 In Pelvic surgery it occurs 55-94%
b) Discuss in more detail intestinal and pelvic adhesions.
Intestinal Adhesion:
Colon inflammation is known to lead to bowel obstructions. Bowel obstruction is a
mechanical blockage of the intestines that prevent regular flow or transit of products
of digestion. Bowel obstruction can result to abdominal pain which is some time the
product of abdominal tissues Adhesion (endometriosis). When growth is present in
the adhesions, it begins to collide with or attach to the walls of the abdomen and other
internal organs. These internal organs may also adhere to one another (increasing the
problem).
Intestinal obstruction is also as a result of abdominal adhesions. This is highly
complex, because the adhesion wraps around the intestine and stops the fluent process
of digestion to occur. This is severe, because it can lead to colon cancer and pelvic
disease, etc….

Pelvic Adhesion:
Pelvic adhesion is fibrous scars that cause infertility which prevents the sperm from
reaching the egg or interfering with fertilization.
These are family adhesion commonly seen after a pelvic infection like pelvic
inflammatory disease. They are easily treated and less likely to recur than the dense
adhesion of endometriosis.
These dense adhesions are commonly associated with advanced endometriosis. They
can be treated with laparoscopy techniques, but are more likely to reform after
surgery.

Chronic results of adhesion:

 Cramp pain to chronic pelvic discomfort
 Bowl obstruction
 Infertility
 Inflammatory disease
1. labia adhesion
2. dyspareunia
 mostly in post surgical activity

c) Describe the properties, mode of action and benefits of In situ cross-linkable

conjugate hydrogels of hyaluronic acid and dexamethasone.

 It is a variety of polysaccharide-based hydrogel barrier systems that have been

used to prevent adhesions.
 Mitigation of pro-inflammatory cytokines release could enhance the prevention of
peritoneal adhesions.
 Anti inflammatory drugs (NSAIDs) such as ibuprofen and glucocorticoids such as
dexamethasone , ( in the hydrogel matrix)
 Injectable hydrogel composed of cross linked modified hyaluronic acids (HAs)
conjugated to dexamethasone (HAX-DEX)
 Inflammatory
 Degraded in media over 5 days, releasing dexamethasone slowly over that time
 HAX-DEX is biocompatible on subcutaneous injection.
  In vivo, the HAX-DEX gel is associated with a lesser inflammatory cell infiltrate
than that from HAX gels.

d) Describe clinical results given in the presentation for the prevention of peritoneum
adhesions in mice and rabbits by using hydrogels consisting of HA and methyl
cellulose (HA-MC).

Peritoneum of mice one week after injection of hydrogels:

HA-MC showed the increase amount of residual material, demonstrated the forceps
submerged beneath it.
HAX no residue

Prevention of peritoneal adhesion in a rabbit abrasion model showed absence of

adhesions after one week in an animal treated with HA-MC

Hydrogel recovered from an animal treated with HA-MC, with inflammatory cells.

16) Extracellular Matrix (ECM) Scaffolds and powder as Materials in Medicine

a) Where is the Extracellar Matrix Scaffold isolated from?

The Extracellar Matrix Scaffold exists in almost all tissues but only can be isolated from
the dermis of the skin, the submucosa of the small intestine, pericardium, Basement
membrane and stroma of the decellularized liver, and the Decellularized Achille’s
Tendon.

b) Discuss snap freezing and enzymatic methods that are used to produce ECM
scaffolds or powder. For each method, what is their mode of action and effects on
ECM? Why is it important to remove cells from ECM before they are used as
scaffolds and powders??)
Physical snap freezing:
Mod of action: intracellular ice crystals disrupt cell membranes
Effect on ECM: ECM can be disrupted or fractured during rapid freezing
Enzymatic
Mode of action: cleaves peptide bonds on the c-side of Arg and Lys.
Effect on ECM: prolonged exposure can disrupt ECM structure; remove laminin,
fibronectin, elastin, and GAGs.

We remove cells from ECM because it would elicit an immune response from the
patient.

c) How do ECM scaffolds facilitate Tissue Regeneration?

• The rationale behind using ECM scaffolds as modes of tissue regeneration is that
these scaffolds will degrade after being implants and then release naturally
occuring growth factors.
• The fibronectin protein in the isolated ECM derived from porcine small intestine
submucosa (SIS) and urinary bladder submucosa (UBS) is responsible for
endotheial cell bioadhesion in xenogenic bioscaffolds.
• Glycosaminoglycans (GAG) bind growth factors, cytokines, water retention, and
the “gel-like” properties of the ECM. Heparin-rich GAGs are important for tissue
repair.
• ECM powder would naturally contain a mixture of growth factors and materials
that are synthetically engineering into common bio-scaffold materials.
• However, dosage and localized release are two factors that affect the efficiency of
this treatment.
d) Describe how an ECM Matrix was used as a myocardial patch?

• The ECM scaffold has potential to replace Dacron ® and Teflon ® as used for
Surgical Ventricular Restoration (SVR) which only serves to restore the
geometrical standards of the heart.
• THE ECM Scaffold in comparison has the ability repair and facilitate the
formation of functional myocardial tissue will be required.
• No infection and aneurysm is present and the patch has helped to develop tissue
that is just as thick as the adjoining right ventricular wall.