Materials Flashcards
What is Biocompatibility?
Multiple definitions. Williams, 1987 described biocompatibility as the ability of a material to perform with an appropriate host response in a specific application.
Ambiguous term since it’s related to the behaviour of biomaterials in various contexts as well as how out insights into their interaction with the body is continually developing
What aspects are considered when describing biocompatibility and examples (3)
The effect the implant material has on the body (ex. proteins absorbed from blood)
The effect the body has on the implant (ex. degraded by the environment of body)
Specific application (ex. hip implant needs to integrate with body and perform function, but tissue engineered scaffold has successful biocompatibility if its bioactive)
How do body cells interact with the material and importance in determining biocompatibility
Interacts indirectly through a protein layer that acts like a synthetic ECM (proteins (mainly fibrinogen) absorbed onto material from blood during implantation and other fluids)
Like in vivo, surroundings of the implant (tissue and material) determines cell behaviour/fate (if it differentiates, migrates, replicates, creates or maintains tissue, etc) and we need it to regulate cell function through similar mechanisms
How may body cells respond to the material depending on biocompatibility
Platelets release cytokines ( // ) that attract immune cells (neutrophils and macrophages) to the material to interrogate through their integrins.
If the immune cells don’t like the biomaterial and protein coat after interrogating, the macrophages will fuse with one another to form giant cells to eat the material (1-5 days).
If they like the material the macrophages will adopt an M2 phenotype for tissue repair. They will recall fibroblasts to form tissue around the implant (fibrous capsule)
Which proteins are absorbed by biomaterial and properties that influences which proteins are absorbed
Proteins highly present from blood (during implantation) and other bodily fluids
Mainly fibrinogen
Also albumin, vitronectin, etc
Platelets also accumulate with the protein layer
Proteins absorbed depends on the materials surface properties: hydrophobicity, if it has a certain amount of roughness, etc
Which properties in extracellular microenvironment determines cell fate and examples (3)
Physical signals (presence of ECM proteins like fibronectin and collagen; softer for adipose, stiffer for bone)
Soluble signals (presence of GF, cytokines, etc)
Cell-cell interactions (cadherins, etc)
Body response when foreign substance is present. Which is activated with biomaterial?
Immune response occurs since material is a foreign substance.
The non-specific innate immune response is activated in the first few hours (0-12) as it is always there. Important in the case of biomaterials.
Then days later the adaptive immunity gives a specific response. The response increases in magnitude with time and has memory (so faster response next time)
Examples of innate and adaptive immunity cells/components and where they come from
Innate:
epithelial barriers (skin, etc) to stop entrance of microbes
complement cascade to add proteins to the foreign substance to other cells can recognise and attack
phagocytes, neutrophils and macrophages that perform phagocytosis
Adaptive:
Lymphocytes (B and T cells)
All immune cells come from bone marrow hematopoietic stem cells
Cells recruited biomaterial is implanted and traits of each cell
First responders are neutrophils which takes minutes to be recruited and only lasts hours; short-lived. They secrete cytokines which attract circulating non-active monocytes.
They which through the endothelial barrier and differentiate into macrophages which stays for hours/days.
Macrophages are the cause of short lived inflammation period after which is ideal. Macrophages can present 2 phenotypes:
-M1 in early stages of repair that’s pro-inflammatory and tissue injury related (creates reactive oxygen and nitrogen species, proteases, cytokines, coagulation factors, etc)
-M2 in the later stages of wound healing that’s pro-repair for tissue healing and remodelling (secretes angiogenic and growth factors like FGF)
Chronic inflammation (persistently active macrophages) leads to rejection of material as macrophages persist.
Importance/role of cytokines for each cell
Damaged cells secrete cytokines to recruit neutrophils
Neutrophils secrete cytokines to recruit macrophages (depending on cytokine profile neutrophils release influences if macrophages differentiate into M1 or M2)
Macrophages secrete cytokines to recruit other macrophages and cells
Normal classical wound healing process (key end goal of the 3 stages) and how it relates to implantation
An injury is made every time a material is implanted
Inflammation (1-2 days) in which there’s the formation of the initial fibrin clot to stabilise the wound, prevent further blood loss and protect from further bacteria/infection
Proliferation (2days to 3weeks) in which there’s formation of new (granulation) tissue as a substrate for cell migration and proliferation of other cells into to form new tissue, vessels, and wound closure
Remodelling (3weeks to years) in which the new tissue is strengthened and refined to restore wound to original state (always a partial loss of complexity and functionality; healing worsens with age)
In the classical wound healing process what occurs at stage 1
Inflammation (1-2 days)
Begins with coagulation cascade:
Platelets are released from blood vessels.
Platelets release cytokines (PDGF, etc) to recall neutrophils (short-lived inflammation).
Fibroblasts are encouraged to divide and invade (polymerised into fibrin clot) and acts as a scaffold for immune cells. Endothelial cells are attracted.
In the classical wound healing process what occurs at stage 2
Proliferation (2days to 3weeks)
- Cells start proliferating (ex. Keratinocytes in skin wound)
- Cytokines released by neutrophils and platelets recall monocytes which activate into macrophages (for wound closure) and endothelial cells (for angiogenesis)
- Cytokines released by all the cells present attract fibroblasts that activate into myofibroblasts (high myosin content) and so can seal the wound.
- Fibroblasts produces collagen which is a structural scaffold that helps hold wound together. Collagen recruits fibroblasts which produces more collagen and other proteins to form the scab.
In the classical wound healing process what occurs at stage 3
Remodelling (3weeks to years depending on tissue. Months if there was chronic inflammation)
Fibroblasts produces collagen which is a structural scaffold that helps hold wound together. Collagen recruits fibroblasts which produces more collagen and other proteins to form the scab.
Apoptosis of endothelial cells, macrophages, myofibroblasts as no longer needed (if they don’t die then a very high fibrotic scar can form which is different from original tissue)
Granulation tissue formed has high collagen III and secretes proteases for remodelling to produce a tissue made of mostly collagen I to increase tensile strength (scar tissues has 80% strength of original)
Ideal goal of regenerative medicine
Bioengineer strategies to prevent the classical wound healing process and restore the original/functional tissue (no scar formation)
Ways to assess biocompatibility
ISO 10993 are the set of international standards the biomaterial must meet that require testing for system toxicity, chemical characterisation, and tests for local effects after implantation
Thickness of fibrous capsule (thin)
Presence of macrophages in fibrous capsule (none)
