Biomaterials

BME 551 / 551EPE Tissue Engineering

Objectives
1. 2. Understand how the definitions for biomaterial and biocompatibility have evolved with time. Discuss how surface chemistry affects cell adhesion and protein adsorption. Know how these events are important to biomaterials development. Compare and contrast bulk degradation and surface degradation. Know the factors that play a role in determining a materials biocompatibility. Discuss the advantages/disadvantages of in vitro and in vivo biocompatibility testing. Describe the general methods by which biomaterials are being designed to be biomimetic. Discuss current strategies for tailoring biomaterials for specific tissue-engineering applications (e.g., modularization, micropatterning, stimuli responsiveness, peptide grafting, etc.)

3. 4. 5. 6. 7.

Biomaterials:
Evolution of definition.
Synthetic material used to replace part of a living system or to function in intimate contact with living tissue A systemically and pharmacologically inert substance designed for implantation within or incorporation with living systems A nonviable material used in a medical device intended to interact with biological systems Materials of synthetic as well as natural origin in contact with tissue, blood, and biological fluids and intended for use for prosthetic, diagnostic, therapeutic, and storage applications without adversely affect the living organism and its components Any substance (other than drugs) or combination of substances synthetic or natural in origin which can be used for any period of time, as a whole or as a part of a system, which treats, augments, or replaces any tissue organ or function of the body

Biomaterials and Medical Devices Limitations

Poor tissue integration No growth or adaptation Adverse reaction (fibrosis) with surrounding tissue Loss of mechanical integrity with time Increased risk of infection Lack of biologically relevant instructive properties

Traditional Biomaterials and Medical Devices

Preformance Criteria Biologically inert Biocompatible Non-viable Mechanical strength and function Amenability to engineering design, manufacturing, and sterilization

.not found naturally within the body

Next Generation Biomaterials and Medical Devices

Revised Preformance Criteria Biologically inert Biocompatible Non-viable Mechanical strength and function Amenability to engineering design, manufacturing, and sterilization Biodegradable Induces cell and tissue integration Smart (i.e., physiologically-responsive) Instructional (i.e., controls cell fate)

Types of Biomaterials
Synthetic (metals, polymers, ceramics, composites) Nature-derived (e.g., plant-derived) Naturally-derived (e.g., tissue-derived) Semi-synthetic or hybrid What are the major factors that contribute to specific biomaterial choices?

Materials and their Medical Uses

Question:
What are the important design criteria when identifying a biomaterial to incorporate as part of tissue engineering design solutions?

Tailoring Biomaterials

Biomaterials: Surface Chemistry

Adhesion properties of cells and proteins is dependent upon surface chemistry (general: hydrophobic, electrostatic, van der Waals, hydrogen bonding, or specific receptor-ligand) Cell Adhesion Protein Adsorption

Cell-Surface Interface
Specific Interactions receptor-ligand Non-specific Interactions hydrophobicity/hydrophilicity Surface topology/architecture Physical

Protein Adsorption
There are three main mechanisms by which surface properties can modify the cell response through protein adsorption: Differential affinity of proteins for different surfaces Modulation of the biological activity of the adsorbed adhesion protein due to conformational changes Substrate activation of a cellular adhesion protein

Immobilization via Adsorption

Covalent Bonding and Graft Polymerization

Self-Assembled Monolayers
Substrate (glass coverslip or silicon wafer) pretreated with a thin layer of titanium (1-5 nm); followed by a thin layer of gold (10200 nm) Adsorption of alkane thiol (R-SH) solution or vapors to gold surface

Self-Assembled Monolayers

Microcontact Printing

Biomaterial Processing
Micromachining Fiber bonding Solvent casting and particulate leaching Membrane lamination Melt molding Electrospinning Extrusion Three-dimensional printing Gas foaming Freeze-drying Polymer/ceramic composite foams In situ polymerization; self-assembly

Electrospinning Process

Electrospinning Collection Schemes