Regenerative medicine for bones

Question 1

What is the difference between tissue regeneration and tissue repair?

Answer 1

Repair - remodelling replaces damaged tissue with an inferior tissue often a scar
Regeneration - expect remodelling to restore native tissue, to previous function and cell type.

Question 2

What is regenerative medicine?

Answer 2

Aims to help the body heal more effectivly to reduce the damage from aging, diseased tissues or organs
Is a multisystem and constantly evolving approach.
Includes cell therapies, artificial organs, natural/synthetic replacements.

Question 3

What two organs in the body are able to regenerate itself and does not scar?

Answer 3

Liver
Bones

Question 4

What are chondral lesions?

Answer 4

Tears in articular cartilage, often found at the knee joint.
Cartilage does not have regnerative capacities so function is lost without treatment.

Question 5

What is a bone callus?

Answer 5

A soft type of bone early in the regeneration stage
Replaces the blood clot after the inflammatory stage of bone healing.

Question 6

What structures aid bones regnerative capacities?

Answer 6

Surrounding muscles have vasculature, supply nutrieints, oxygen and inflammatory mediators.

Question 7

What is the composition of the bone ECM?

Answer 7

35% organic - 90% type 1 collagen, ground substance and GAGs
65% inorganic - mainly hydroxyapatite (mineral)

Question 8

Where in a bone are bone fractures most common why?

Answer 8

Fractures are most common in the shaft because this has a larger proportion of spongy rather than cortical bone compared to the head.

Question 9

Why are central canals or haversian canals important to bone strength?

Answer 9

Larger number of canals increases the porosity of bone
Greater porosity decreases strength.

Question 10

What are the prerequisites for bone healing?

Answer 10

Adequate blood supply
Adequate mechanical stability.

Question 11

Desribe the blood supply of a long bone

Answer 11

Nutrient arteries -start in the centre of the diaphysis, have ascending and descending branches, supplies the bone marrow and the inner 2/3 of the cortex, ends become spiral branches with anastamose with metaphysial arteries

Metaphysial arteries - rich blood supply to the metaphysis

Epiphysial arteries - supply epiphysis, enastamose with meta in adults

Periosteal vessels - low pressure system supply outer 1/3 of cortex.

Question 12

What are the two difference mechanisms of bone healing?

Answer 12

Direct bone healing
indirect bone healing

Question 13

Give an overview of direct bone healing.

Answer 13

No motion at the fracture site
No callus formation
Slower form of healing
Progress is not shown on an x-ray
Often occurs after surgery after point welding of the bone

Question 14

Give an overview of indirect bone healing.

Answer 14

Motion at the fracture site
Callus formation after an inflammatory cascade
Rigid fixitive is not used
Easier to monitor on an x-ray
Faster healing process but can be more painful.
natural type of healing

Question 15

What is the process of direct bone healing?

Answer 15

1. Fracture compression and internal fixation
2. Gap healing - osteoprogentitor cells and blood vessels fill the gaps, if gaps are primary bone is often formed first and remodeled to become cortical.
3. Contact healing - cutting cone mechanism, osteoclasts degrade small portions of bone to create pathways for osteoblasts and osteoprogenitor stem cells.
   Late osteon formation

Question 16

What is the process of indirect bone healing?

Answer 16

1. Tissue destruction and haematomoa formation - due to torn blood vessels,
2. inflammation - acute inflammation, haematoma is fully clotted absorbed and capillaries grow into the area, MSC from periosteum and medullary canal start to proliferate. Phagocytosis of dead material
3. Soft callus - clotted, depedning on the environment MSC becomes fibroblasts, osteoblasts or chondroblasts, osteoclasts from blood vessels clear the damaged bone, replaced by fibrocollagenous structure and cartilage, lumps of immature bone and cartilage form callus. Fracure ends movement reduced
4. Hard callus - osteofication starts, endochondral or intermembranous, calcification of ECM
5. Bone remodelling - this crude bone is reshaped by the combined action of osteoclasts and osteoblasts, froms spongy and cortical bone

Question 17

What is the healing cascade of indirect healing of bone?

Answer 17

Inflammation: haematoma, necrotic material is phagocytosed
Repair: granulation tissue (new CT and BV), acidic environment, osteoclasis if needed
Later repair: fibrous tissue replaced by cartilage, endochondral ossification, periosteal healing then allows membranous ossification.
regeneration and remodelling: Mechanical strain on bone, callus replaced by primary then secondary bone.

Question 18

What is osteoclasis?

Answer 18

The breaking of bone to help solve deformity.

Question 19

What is articular cartilage made of?

Answer 19

65-80% water, decreases with age and over the course of a day, increases with rest - hydrophilic provides turgor
type 2 collagen
Proteoglycans
Chondrocytes
Matrix components.

Question 20

What type of cartilage injuries are common in children?

Answer 20

Growth plate injuries at the tide mark.

Question 21

Why does cartilage not heal?

Answer 21

Chondrocytes are imprisoned in collagen and proteoglycan ECM, difficult to communicate to
Avascular - very poor nutrients supply.

Question 22

What are the different surgical options for cartilage repair?

Answer 22

Marrow stimulation techniques (abrasion athroplasty, subchondral drilling and microfracture)
Osteochondral autograft transfer (mosaicplasty)
Osteochondral allograft transfer
Autologous chondrocyte implantation

Question 23

What is meant by lavage and debridement in cartilage repair techniques?

Answer 23

Wash out the joint, remove debris and file sharp surfaces
Temporarily removes inflammatory mediators and bradykinins from the area, relieves symptoms in the short ter, for 60% of people
Patients must have a low BMI, stable ligaments, minimal malalignments and low energy trauma.

Question 24

How does microfracture work to treat cartilage damage?

Answer 24

Is a marrow stimulation technique.
Loose cartilage, bone and calcified layer are removed
Holes or microfractures are drilled through the bone into the bone marrow
The bone marrow will bleed
Result in a fibrocartilage scare, this is better than no cartilage but still has different properties to hyalin cartilage

Question 25

What is a mosaic plasty in treatment for cartilage damage?

Answer 25

Used for younger patients with large and deep cartilage damage
Damaged cartilage is removed.
Healthy cartilage is taken from non-weight bearing areas as small cores
Cores are inserted into the site of damage in a mosaic patterns
Bone marrow between the cores is exposed, heals as fibrocartilage between the hyaline cores.

Question 26

What is the OATS procedure for treatment of damaged cartilage?

Answer 26

Similar to the mosaic system.
Cartilage is taken from elsewhere in the body
Damage cartilage removed and new cartialge core is added
Unlike mosaic only one cartilage core is added.

Question 27

What is an osteochondral allograft transplantation?

Answer 27

Damaged cartilage is replaced by healthy cartilage from a donor.

Question 28

What is autologous chondrocyte implantation?

Answer 28

Self articular cartilage cells are collected and grown in a laboratory
Reinstituted into the joint at a later date, replacing damaged cartilage, given time to heal and grow into the space.