Biomedical Engineering Reference
In-Depth Information
results in enhanced cellular attachment and cellular function, and has motivated increased
research on nanostructured biomaterials.
Instead of making porous scaffolds in which the cells are seeded onto the surfaces,
another approach in tissue engineering for cell or growth factor delivery is hydrogel scaf-
folds that enclose the cells while allowing fluid and gas transport. Hydrogels can be formed
from a vast array of natural and synthetic materials. Hydrogels made of natural materials
such as collagen, hyaluronan, alginate, and chitosan are inherently biocompatible and bio-
active. They may promote many cellular functions due to the myriad of growth factors and
cytokines present in the natural materials. However, as with any natural material, the draw-
back is lot-to-lot variability, which makes it difficult to study biological responses to small
chemistry modifications, so fully synthetic molecules such as polyethylene glycol hydrogels
are better suited for fundamental studies of cell physiology.
The variables within a hydrogel that can affect the cell viability and function include the
type of cross-linker and the amount of cross-linker, which further define the mechanical
properties, and transport and degradation kinetics. In vivo, the extracellular matrix provides
a milieu of binding ligands for cell adhesion. These ligands encourage cell receptor-ligand
events that communicate the mechanics of the extracellular matrix to the cell and direct cell
fate through intracellular signaling pathways. To accomplish this within synthetic hydrogels,
small amounts of extracellular matrix proteins such as collagen, laminin, or fibronectin are
incorporated into the network.
5.6 SAF
ETY TESTING AND REGULATION OF BIOMAT
ERIALS
5.6.1 Product Characterization
Ensuring product purity and identity is one of the first steps in developing a safe prod-
uct. There are extensive data documenting the safety of various biomaterials, but since pro-
cessing methods may include additives and the final sterilization step may alter the
biomaterial, it is crucial to always verify the end product purity and identity. The American
Society for Testing and Materials (ASTM, www.astm.org) has developed many standards
that manufacturers of medical device products can use as guidelines to evaluate product
purity and identity, as well as safety. Under ASTM specifications for metals used in medical
devices, there are restrictions on the composition, microstructure, phase and grain size,
inclusion size, defect size, and macro- and microporosity to help ensure safety. There are
ASTM standards for ceramic materials that specify chemical composition, phase determina-
tion, grain size, and impurities such as sintering aids, which may decrease fatigue resis-
tance. New standards are being written by ASTM, which has created a new division to
help ensure quality and reliability of tissue engineering scaffold materials. In addition to
specifying the correct tests and techniques to determine the chemical identity of the tissue
engineering scaffold materials, standardized tests for measuring porosity and permeability
have also been developed. ASTM also has standards for dissolution testing, degradation
testing, and stability testing. ASTM standards are written through a consensus process
and represent the best available knowledge from a wide cross section of manufacturers,
