Inflammation Inflammation is the reaction of vascularized living tissue to injury. The inflammation process includes a sequence of events that can heal the implant site. This is done through the generation of new tissue via its native cells or the formation of fibroblastic scar tissue. Some processes during inflammation Enhanced permeability of vasculature Fluid, proteins, blood cells escape vascular system into the injured tissue Blood clotting --thrombosis is possible Cell response--neutrophils (24-48 hrs) Monocytes macrophages (months)

Acute vs Chronic Inflammation Inflammation almost always occurs. Distinguished not only by the time course of the inflammatory response, but also by Cellular interactions Acute inflammation, which is typical of early phases of the inflammatory response, involves neutrophil leukocytes as the principal cellular effectors. Chronic inflammation, which tends to occur over a longer time, involves monocytes, macrophages, lymphocytes

The macrophage is a key cell in the inflammation process as it can produce a large number of biologically active products including proteases, complement components, coagulation factors, growth factors and cytokines (proteins that regulate immune response).

Biological Response

Granulation Tissue Granulation tissue is the fibrous connective tissue that occurs in healing wounds. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size it heals. Granulation tissue is composed of tissue matrix supporting a variety of cell types, most of which can be associated with one of the following functions: extracellular matrix, immune system, or vascularisation

Types of granulation tissue Extracellular matrix The extracellular matrix of granulation tissue is created and modified by fibroblasts. Initially, it consists of a network of Type III collagen, a weaker form of the structural protein that can be produced rapidly. This is later replaced by the stronger, long-stranded Type I collagen, as evidenced in scar tissue. Immunity The main immune cells active in the tissue are macrophages and neutrophils. These work to phagocytize old or damaged tissue, and protect the healing tissue from pathogenic insult. This is necessary both to aid the healing process and to protect against invading pathogens, as the wound often does not have an effective skin barrier to act as a first line of defence. Vascularization It is necessary for a network of blood vessels to be established as soon as possible to provide the growing tissue with nutrients, to take away cellular wastes, and transport new leukocytes to the area. Fibroblasts, the main cells that deposit granulation tissue, depend on oxygen to proliferate and lay down the new extracellular matrix.

Granulation tissue process Within 24 hrs of implantation, healing initiated by the action of monocytes and macrophages. Fibroblasts reproduce and form granulation tissue (pink, granular appearance) Neovascularization involves the generation, maturation, and organization of into capillary tubes. Fibroblasts are active in the synthesis of Collagen etc. Granulation tissue may be observed within 3-5 days of implantation of a biomaterial—it is often accompanied by wound contraction.

Foreign Body Reaction Indicated by the presence of multinucleated foreign body giant cells and the components of granulation tissue (macrophages, fibroblasts, and capillaries) Surface of the biomaterial will often determine the composition of the foreign body response

Surface structure important for biocompatibility High surface to volume ratio of fabrics and porous structures can result in higher ratios of macrophages than a smooth component made of the identical material but can also encourage tissue ingrowth --this is observed in vascular grafts.

Fibrosis and Encapsulation The final stage of the foreign body response and healing process is the development of a fibrous encapsulation Repair involves two separate processes: replacement of tissue by parenchymal cells of the same type or replacement by connective tissue that constitute the fibrous capsule. These processes are controlled by the growth capacity of the cells in the tissue receiving the implant, the persistence of the tissue framework and degree of injury.

Host can affect the implant Physically Abrasive, adhesive, delamination wear Fatigue and Fracture Stress Corrosion cracking General corrosion Biologically Absorption of substances from the tissues Enzymatic degradation Calcification Some Host Factors: Age and health status Immunological/metabolic status Choice of surgeon: minimize tissue damage and contamination, proper implantation

Implant Factors Bulk properties: chemical composition, structure, purity and presence of leachables. Surface properties: smoothness, COF, geometry, hyrophilicity, surface charge Mechanical properties: match properties of component being replaced, such as elastic modulus. Stability and fixation. Long-term structural integrity: design for fatigue and fracture loading, wear, creep, and stress corrosion cracking

Bioactivity spectra for bioceramics

Biocompatibility testing Cell toxicity Thromobogenecity Inflammatory response Animal tests Clinical trials FDA regulations ASTM/ISO standards