inflammation and wound healing Flashcards
Platelet activation via adsorbed proteins
trigger: adsorption of plasma proteins on material surfaces
effect: platelet adhesion, activation, aggregation
primary players: platelets and adsorbed proteins (fibrinogen, vWF)
end product: platelet plug formation
hemostasis phase: primary
material properties driving it: protein adsorptive surfaces
contact activation of intrinsic clotting cascade
trigger: direct activation of factor XII by the material surface
effect: initiates fibrin formation via the intrinsic coagulation cascade
primary players: coagulation factors, fibrin formation
end product: fibrin clot stabilization
hemostasis phase: secondary
material properties driving it: reactive/negatively charged surfaces
competitive protein binding in biomaterial-tissue interactions
describes how proteins from body fluids (eg blood plasma) compete to adsorb onto the surface of an implanted biomaterial
protein adsorption and cellular response (biomaterial-tissue interactions)
Upon implantation, proteins rapidly adsorb onto the material surface, forming a “protein corona” that acts as the interface between the biomaterial and the biological environment. The composition of the protein corona determines cellular behavior, immune responses, and biocompatibility. Examples:
* Fibrinogen promotes immune cell adhesion and triggers inflammation.
* Albumin supports a more biocompatible surface.
vroman effect
Initially adsorbed proteins (often abundant, low-affinity proteins) are displaced by higher-affinity proteins over time, altering the biological response to the material.
material properties (competitive biomaterial-tissue interactions)
Surface features like charge, hydrophobicity, and roughness dictate protein binding and downstream biological effects.
improving blood compatibility of article surfaces
hydrophilic coatings, anticoagulant coating, NO releasing surfaces, protein immobilization, drug-eluting surfaces, biomimetic materials, nanostructured surfaces
Approach: hydrophilic coatings
Create a hydrated layer to repel protein and platelet adhesion (e.g., PEG-based).
approach: anticoagulant coating
e.g., heparin, which binds antithrombin III to inhibit thrombin and reduce clot formation.
approach: NO releasing surfaces
Mimic endothelial cells by releasing NO, which inhibits platelet activation and aggregation.
approach: protein immobilization
Immobilize proteins like albumin to form a non-thrombogenic interface.
approach: drug-eluting surfaces
Release antiplatelet or anticoagulant drugs (e.g., sirolimus, paclitaxel).
approach: biomimetic materials
Incorporate endothelial-like molecules (e.g., thrombomodulin) to mimic natural blood vessel surfaces.
approach: nanostructured surfaces
Modify surface roughness to reduce platelet adhesion and activation.
biological responses to materials ex. tissue reactions
Beneficial: A vascularized tissue reaction, a thin fibrous capsule, and integration of the material with the surrounding tissue resulting in a seamless continuity within the tissue.
Deleterious: Thick fibrous and avascular capsule, scar formation, and chronic inflammatory response.
tissue homeostasis
Tissues operate best within specific physiological ranges (e.g., pH,
temperature, nutrition, pressure).
The body maintains homeostasis (optimal conditions) by dynamically adapting to internal and external changes.
mechanisms of adaptation (tissue homeostasis)
achieved through:
- soluble signaling molecules (eg hormones, cytokines)
- cell-cell and cell-ECM interactions
ECM role
three-dimensional network of proteins, glycoproteins, and polysaccharides that provides structural and biochemical support to surrounding cells in tissues.
Tissue homeostasis depends critically on cellular interactions with the extracellular matrix (ECM).
Extracellular matrix (ECM)
In most tissues, the ECM is constantly turning over and being remodeled in a coordinated, regulated manner.
ECM turnover is generally quite low in normal mature (i.e. stable) tissues, but rapid and extensive remodeling characterizes embryological development, adaptation to changing environmental conditions, and wound repair.
Tissues with high regenerative capacity
- Epithelial, lymphoid, hematopoietic, and mesenchymal tissues (cell types include fibroblasts, smooth muscle cells, osteoblasts, chondrocytes, and endothelial cells)
- Highly vascularized
Tissues with low regenerative capacity
Nerve, muscle (esp. cardiac), cartilage
homeostasis and hemostasis
Hemostasis is a critical part of homeostasis because it helps maintain blood pressure and other factors that are important for survival.
The coagulation system, which is responsible for blood clotting, is tightly controlled to ensure a balance between clotting and vascular integrity.
Immune system
defends the body by protecting against harmful pathogens, maintaining self-tolerance, and coexisting with beneficial microbes.
complex network of cells, tissues, and molecules that protects the body from infections and maintains homeostasis.
Immunology is now recognized as vital for tissue homeostasis, influencing stem cells, local metabolism, and the microbiome.
Immune system main branches
- innate immune system
- first line of defense, providing a rapid but non-specific response.
- Includes physical barriers (skin, mucosa), cells (macrophages, neutrophils, natural killer cells), and soluble factors (cytokine, complement proteins) - adaptive immune system
- provides a slower, highly specific response
- involves T cells and B cells, which recognize and remember specific pathogens
- includes the production of antibodies by B cells
Complement system core functions
Complement activation through the classical, lectin, and alternative pathways, leading to the formation of the membrane attack complex (MAC) which can directly kill pathogens.
complement system beyond pathogen killing
Recent research highlights the Complement System’s role in regulating inflammation, influencing adaptive immune responses by interacting with T and B cells, and contributing to tissue homeostasis.
complement system emerging complexities
Further investigations include the role of complement receptors on immune cells and the potential for dysregulation in autoimmune diseases.
Complement system overview
complex cascade involving approximately 30 glycoproteins present in serum as well as cell surface receptors.
part of innate immune system to enhance the immune system’s ability to clear pathogens and damaged cells; it also bridges to the adaptive system by enhancing antibody responses.
complement system key functions
Opsonization: Coating pathogens to enhance phagocytosis.
Chemotaxis: Attracting immune cells to the infection site.
Lysis: Forming the membrane attack complex (MAC) to lyse pathogens.
Inflammation: Triggering the release of inflammatory molecules.
complement system activation pathways
Classical Pathway: Activated by antibodies binding to antigens.
Lectin Pathway: Triggered by mannose-binding lectin binding to microbial surfaces.
Alternative Pathway: Spontaneously activated on pathogen surfaces.
