OE L42 Implantology: Soft Tissue Healing

Question 1

Describe the vascular response after implantation.

Answer 1

Day 0:

• Trauma to tissues causes bleeding
• Vascular smooth muscle cells contract to reduce size of lumen (vasoconstriction)

Question 2

Describe haemostasis after implantation.

Answer 2

Day 0:

• Platelets are exposed to ECM causing them to form a platelet plug
• Platelets contain proteins and GFs (e.g. von Willebrand factor, Il-6, PDGF, TGF-β) which attract other cell types to cause wound healing
• Clotting pathway: conversion of soluble fibrinogen to insoluble fibrin

Question 3

Describe inflammation after implantation.

Answer 3

• “Cleaning the wound”
• Performed by leukocytes e.g. neutrophils, lymphocytes, eosinophils
• Large concentration of GFs and cytokines on the endothelial cell surface which acts as chemoattractants
• Chemoattractants cause integrin expression on the endothelial cell walls
• Integrins are receptors which capture the leukocytes and roll them until they’re located opposite the wound
• Transmigration of leukocytes into wound between the endothelial cells

Question 4

Describe the action of neutrophils and macrophages in the wound.

Answer 4

Neutrophils:

• First cell type attracted to wound site
• Phagocytose bacteria, cell debris, matrix debris

Macrophages:

• M1 type
• Second line of defence
• Differentiate from monocytes
• Phagocytose bacteria and debris

Question 5

Describe fibroblast migration in wound healing.

Answer 5

Days 1-7:

• Fibroblast migration
• Inflammatory GFs attract fibroblasts (e.g. PDGF, EGF, TGF-β)

Other factors also cause migration:

• Decreased oxygen tension
• Damaged ECM (collagen fragments sensed)
• Decreased ECM tension detected by integrin receptors

Question 6

Describe fibroblast proliferation in wound healing.

Answer 6

Days 3-14:

• Fibroblast proliferation
• Stimulated by paracrine GFs (PDGF, TGF-β) and autocrine GFs (FGF)
• Also stimulated by ECM components e.g. hyaluronan, fibronectin

Question 7

Describe granulation tissue formation in wound healing.

Answer 7

Days 4-21:

• Fibrin plug is broken down by fibrinolysis
• Granulation tissue is produced by fibroblasts

Question 8

What type of collagen is present in the healed tissue?

Answer 8

• 80-90% Type I collagen: provides tensile strength and cell adhesion sites
• 10% Type III collagen: present in early wound matrix

Question 9

What are the role of types IV and VII collagens in wound healing?

Answer 9

• Reformation of the basement membrane

- Important in keeping endothelial or epithelial structures attached to the underlying tissue

Question 10

What is the role of fibronectin found in the ECM?

Answer 10

• Found in early wound healing

- Has many binding sites for cells, GFs, other ECM components

Question 11

What is the role of proteoglycans/GAGs found in the ECM?

Answer 11

• Proteoglycan is the backbone to which GAGs attach to
• Fill the wound space and give resilience to the tissue
• Hydrophilic, retain lots of water

Question 12

What is the role of glycoproteins found in the ECM?

Answer 12

• Binding motifs for other molecules
• Roles in cell recognition, adhesion, migration and proliferation
• E.g. tenascin, vitronectin, laminin

Question 13

What components are found in high concentrations in granulation tissue?

Answer 13

• Type I and III collagen
• Fibronectin
• Hyaluronan

Question 14

What are cytokeratins?

Answer 14

Keratin found in the cytoplasm of the cell.

Question 15

How do epithelial cells connect to eachother?

Answer 15

• Adhesion, tight and gap junctions

- Gap junctions allow rapid communication via signals between cells

Question 16

What is the most superficial layer of a keratinised epithelium?

Answer 16

• The stratum corenum aka cornified envelope

Question 17

What connections keep the basement membrane connected to the unerlying mesenchyme/lamina propria?

Answer 17

Hemidesmosomes

Question 18

How does angiogenesis occur during wound healing?

Answer 18

• Occurs from existing blood vessels
• Endothelial cells migrate towards the wound and proliferate
• 2 of the growing vessels meet and link together, forming a vascular loop
• Ultimate formation of a capillary network

Question 19

After granulation tissue forms, the ECM is remodelled and the final tissue established. Which cell is key to matrix remodelling?

Answer 19

Myofibroblasts

• Contain smooth muscle actin, non-muscle myosin and fibronexi on their cell surfaces (where thousands of integrin receptors meet together in a single spot)
• Allows cell contraction
• Reduces overall wound size, however does cause scar tissue formaiton

Question 20

Which enzymes are involved in matrix remodelling?

Answer 20

MMPs

• Collagenases, stromelysins, matrilysins, membrane-type MMPs
• Degrade all components of the ECM
• Inhibited by tissue inhibitors of MMPs (TIMPs)

Question 21

What causes scar tissue?

Answer 21

The malalignment of matrix molecules.

Question 22

What components are found in high quantities in remodelled ECM?

Answer 22

• Type I collagen
• Elastin
• Sulphated proteoglycans

Question 23

Why does the oral mucosa heal with minimal scarring compared to skin?

Answer 23

• Different type of fibroblasts with different origin (younger, act for longer, antibacterial, immunosuppressive capabilities)
• Inflammatory phase is optimised to reduce scarring, cells respond in ideal way (not too much or too little)

Question 24

Name the 6 stages of soft tissue reapair.

Answer 24

1) Haemostasis
2) Platelet plug
3) Inflammation
4) New tissue formation (granulation)
5) Re-epithelialisation
6) ECM remodelling

These processes are not discrete, they’re all overlapping

Question 25

What biological seal is key to implant success?

Answer 25

• Biological seal at the mucoperisoteal-implant interface
• Provides barrier against ingress of oral toxins and bacteria
• Junctional epithelium critical to a good seal

Question 26

Name 5 reasons for implant failure.

Answer 26

• Improper surgical technique
• Incorrect implant material
• Too much loading
• Bacterial load (poor hygiene)
• Smoking (affects ECM production and inflammation)