Lecture 5

materials that are biocompatible during the time of material-bio system contact. TIME SCALE is very important

1) Blood Supply: Sufficient blood supply is essential for tissue healing and the integration of implants. 2) Infection: Bacterial or viral infections in the vicinity of an implant can be a severe threat. Infections can lead to implant failure by causing inflammation, tissue damage, and bone resorption. 3) Biomechanical Forces: The forces and stresses that an implant is subjected to in its specific location can influence its long-term stability / how the tissue grows.

1) biocompatible : no negative influence on body, generates the most appropriate beneficial cellular / tissue response 2) bioincompatible : release of substances in toxic concentrations -> negative reaction 3) bioinert : almost no chemical / biological interaction with body 4) bioactive : positive tissue differentiation (chemical bonding) 5) biodegradable : tissue replaces implant over time 6)biotolerant : weak tissue reactions (fibrous capsule)

1) tissue response (inflammation, fibrous capsule,…) 2) osseointegration 3) infection 4) stress shielding

Platelets are triggered by foreign material -> blood clot (thrombus) forms on artificial surface. Problems with stents or heart valves for example (restenosis).

starts at periosteum and endosteum. First blood clot, then callus formation (cartilage), then endochondral ossification (woven bone), then remodelling over time

healing process is the same, but foreign material is present when implant

in material : atoms, defects, crystal structure, grains, surface roughness, geometrical design biosystem : aminoacids, proteins, cell membrane, cell, tissue

gap between implant and tissue closes over time -> create a stable interface. First, there is biofluid in the gap (water, proteins, …) and then the tissue grows towards the implant

Phase 1 hemostasis : platelets to stop the bleeding and create provisional matrix. Phase 2 inflammatory : - endothelial cells move apart - leukocytes go through the gaps to the injury site and kill bacteria - macrophages : phagocytosis and stimulate angiogenesis and fibroblasts Phase 3 proliferative : - fibroblasts synthesize ECM components - perivascular cells : angiogenesis, differentiate into osteoblasts (and fibroblasts) - osteoclasts : resorb bone and create space for healing - osteoblasts : form new bone (woven bone) Phase 4 remodeling : - osetoclasts resorb woven bone and osteoblasts lay down lamellar bone - osteocytes regulate that process

adsorbed water + ions : create bonding sites and structures for proteins proteins : have amino acid sequence that the cell will recognize and attach to (integrin on cell recognizes ONLY surface-bound protein) cells : can then proliferate or differentiate -> this gives a hint about biocompatibility (if the cells are happy or not)

It is important for the survival of the cells and to avoid a reaction from the body. It can be changed by biofunctionalization of surface : add RGD peptide sequence to surface -> surface becomes biomimetic and cell adhesive

1) in-vitro: - first the material itself (mechanical properties, …) - then cytocompatibility (assembly) 2) in-vivo : - material - assembly 3) clinical trials (humans) - monocenter - multicenter

1 : evaluation and testing 4 : selection of teste for interactions with blood 5 : tests for in-vitro cytotoxicity

1) direct or indirect patient contact 2) material composition : equivalence with a commercially available product ? (manufacturing, composition, geometry, …) 3) preliminary assessment (sufficient data ?) 4) final assessment : perform further tests

implantation site and implantation time. ex : surface device, external communicating device, implant device

polymers : - differential scanning calorimetry - x-ray diffraction - spectroscopy - XPS metals : - x-ray diffraction - XPS - x-ray fluorescence ceramics : - x-ray diffraction - x-ray fluorescence - microscopy

1) in vitro pro: - controlled environment - fast and effective - sensitive quantification of cellular reactions con: - too simple - bad representation of physiological conditions - cannot replace in-vivo (only one cell type) 2) in-vivo pro: - good simulation of human condition - interaction of different cell types - immune response con : - ethics - expensive and time-consuming - demanding protocols

• rate of adhesion • metabolic activity • cell proliferation • cell morphology

• rate can be weak or strong • metabolites can be changes or unchanged • they can die or proliferate • they can be globular or outspread

test how the mechanical forces regulate cell differentiation and tissue formation. Test force transmission in scaffold. Important in spinal disks for example.

HA = Ca10(PO4)6(OH)2 TCP = Ca3(PO4)2

primary : from patient directly -> need a lot to compare outcomes continous : after in while in culture -> more standardized but act in less natural way