Fracture repair + wound healing

week 10

fracture

fracture

a break in a bone from force applied that exceeds its tensile or compressive strength

causes of bone fractures

1. Fractures caused by sudden injury

2. Fatigue or stress fractures

3. Pathologic fractures

complete fracture

bone is broken all the way through

incomplete fracture

bone is damaged but still in one piece

closed (simple)

Non-communicating wound between bone and skin

Open (compound)

Communicating wound between bone and skin

Comminuted

Three or more bone fragments

Oblique

Fracture line at an angle to long axis of bone

Transverse

Fracture line perpendicular to long axis of bone

Pathological

Fracture at a point where bone has been weakened by disease (e.g. by tumours or osteoporosis)

Compression

Fracture wedged or squeezed together on one side of bone

Displaced

Fracture with one, both or all fragments out of normal alignment

Greenstick

Incomplete

Break in one cortex of bone with splintering of inner bone surface; commonly occurs in children

Stress

Incomplete

Microfracture

direct/primary bone healing

• micro gap <1mm:

  • little to no callus formations

  • Haversian remodelling osteoblast/osteoclast activity

• when bone ends are held close together → intramembranous bone formation

indirect/secondary bone healing

• gap >1mm: callus formation

• more common than direct healing and involves endochondral healing

heals in four phases:

1. Haematoma Phase

2. Inflammatory Phase

3. Reparative Phase

4. Remodelling Phase

fracture: phase of secondary healing?

Phases 1-2: haematoma and inflammatory phase

hours - days

(haema-toma=blood-cut: pool of clotted blood outside the blood vessel)

fracture: phase of secondary healing?

Phase 3 - reparative phase

days - weeks

fracture: phase of secondary healing?

Phase 4 - remodelling phase

months - years

components of tissue repair

• Cells

• Cytokines & Growth factors (GF)

• Extracellular matrix (ECM)

types of cells in tissues

• labile

• stable

• permanent

labile tissues

• high turnover and good proliferative capacity

• continuous replacement by stem cell proliferation

• e.g. skin

stable tissues

• slow or limited proliferation rate

• cells only proliferate when injured

• e.g. liver

permanent tissues

• non/minimally proliferative

• terminally differentiated cells

• not sufficient to replace lost tissue

• e.g. cardiac muscle cells

extracellular matrix

• Intact or preserved ECM is important for regeneration otherwise healing occurs by scar formation (fibrosis)

• 2 basic components:

  • Interstitial matrix

  • Basement membrane

• scaffold for tissue repair

• reservoir of growth factors

• Cross linking of collagen is Vitamin C dependent

interstitial matrix

• amorphous gel-like structure suspending cell/tissue types

• between epithelial and endothelial tissues

• Loose or dense connective tissue

basement membrane

• surface structure supporting tissues

• holds epithelial and endothelial tissues

healing by regeneration/re-epithelialisation

• Stem cells proliferate to replace the damaged cells

• Labile cells, minor injury, clean/sutured cuts

• No/minimal residual damage

• e.g. skin, fetal tissue, GIT, endometrium, bone marrow

healing by scar formation

• Stable or permanent cells, large defects,
  contaminated wounds

• Fibrous tissue to fill the defect: Scar formation/fibrosis

• Enough structural strength but loss of function

• e.g. liver, kidney, brain, muscle, bone

primary intention healing

• Minor, clean, sharp cuts or sutured incisions

• edges close together

• Re-epithelialisation → scarring

• e.g. superficial cuts, most surgical incisions

secondary intention healing

• Large defects

• Wound kept open to granulate, slow healing

• more scarring → moderate re-epithelialisation

• Packed with gauze/VAC/drains to enhance healing process

• e.g. any -ectomy, tooth extraction sockets, compound fractures, venous ulcers, pressure sores

tertiary intention healing

• defect too large and contaminated

• medical intervention

• delayed primary closure:

  • Wound is cleaned

  • edges debrided and kept open for 4-7 days

  • Secondary healing begins/granulation appears

  • surgically: edges brought closer

• E.g.: Tissue grafting sites, highly contaminated/infected, ischaemic/necrotic, etc.

stages of wound repair (superficial, non-complicated wound)

1. Haemostasis Phase/tissue injury: day 0

2. Inflammatory Phase: days 1-2

3. Proliferative Phase: days 3-5

   • formation of granulation tissue

   • angiogenesis: formation of new blood vessels

4. maturation phase: 4-24 days

   or

   secondary intention: scar formation: day 7

granulation tissue

• Pink granular tissue at the wound base (floor)

• Granularity due to new vessel buds

  • felt as knobs

  • blood flow → increased pink/red colour to tissue

• New vessels are thin and fragile hence leaky

  • serum in oedematous loose ECM

• Pink base with some serous ooze – moist wet wound = healthy

primary intention wound strengthening time period (when can I lift /go back to heavy work?)

• 10% strength - 1 week

• 80% strength - 3 months

secondary/tertiary intention wound strengthening time period (when can I lift /go back to heavy work?)

• 10% strength - months to a year

• 80% strength - many years to never

steroids and wound healing

• inhibit the activity of matrix metalloproteinases (MMPs), enzymes critical for extracellular matrix (ECM) remodeling

• leads to weak or delayed ECM repair/epithelialisation

wound healing depends on

• Wound type

• Cell/Tissue type: Proliferative capacity

• Growth factors

• Preservation of ECM

• Healing factors

• Nutritional status (important for collagen synthesis, e.g. vitamin c for collagen maturation and cross-linking)

malunion

two broken edges at the ends of the bones are not aligned

bone heals in awkward position

nonunion

the bone fragments are not healing together

no replacement of lost bone - gap persists

day? stage?

• inflammation

• first couple of days

note: scab formation starts within first few days and persists until 3-5

stage?

• ulcer, serous discharge

• proliferative: granulation tissue (little unhealthy)

stage? day?

• scab is off

• some swelling but not confined to injury site

• maturation/scar formation:

  • granulation almost gone

  • start of re-epithelialisation

• 7 days or more

stage? day?

• tissue stabilised

• puckered border: scar has contracted

• weeks-a month

type of healing

secondary bone healing

Hypertrophic scar

raised scar due to collagen overproduction

scar remains within the boundaries of the wound

keloid

raised scar due to collagen overproduction

scar extends outside the boundaries of the wound

scar formation stages

1. Laying of connective tissue on the granulation tissue/loose ECM scaffold

   • Myofibroblasts migrate and proliferate

   • Deposition of ECM

   • Inhibit collagen degradation

   • Cells: macrophages, mast cells and granulation tissue cells

   • Growth factors: TGF-β, PDGF, FGF-2 and

   • Cytokines: IL 1, IL-13

2. Remodelling of connective tissue: wound strengthening

   • Balance between MMPs (collagen degrader) and TIMPS (collagen degradation inhibitor) regulates repair process

hypertrophy

increase in cell size

metaplasia

change in cell type

hyperplasia

increase in cell number

atrophy

decrease in cell size or number

intramembranous bone formation stages

1. ossification centre formation

   • mesenchymal cells differentiate into osteoblasts

2. secretion of osteoid (matrix)

   • osteoblasts secrete osteoid

   • mineralised within days

   • trapped osteoblasts → osteocytes

3. formation of woven bone and periosteum

   • osteoid calcifies → forms trabeculae

   • vascularised mesenchyme condenses externally → periosteum

4. formation of bone collar and appearance of red marrow

   • Trabeculae deep to periosteum thickens, forming woven bone collar (later replaced by lamellar bone)

   • Spongy bone persist, vascular tissue becomes red marrow

endochondral bone healing

• indirect/secondary bone healing

• interstitial growth from epiphyseal plate:

• Zone of Resting (Reserve) Cartilage:

  • Chondrocytes are small, inactive, and serve as a reserve for future growth.

• Zone of Proliferation:

  • Chondrocytes actively divide and form columns, increasing the length of the cartilage.

• Zone of Hypertrophy:

  • Chondrocytes enlarge (hypertrophy), and their lacunae expand.

• Zone of Calcification/Degeneration

  • The cartilage matrix becomes calcified, and the chondrocytes die, leaving spaces for bone-forming cells.

• Zone of Ossification:

  • Osteoblasts invade the calcified cartilage and deposit bone matrix, converting cartilage into bone tissue.