Cell/Tissue - Biomaterial interaction
Biomaterial: "any substance (other than a drug) 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"
The National Institutes of Health Consensus Development Conference, 1984
Wound healing process
1. Haemostasias
mechanical barrier, retention of moisture, absorption of exudates, anti-coagulant
2. Inflammation
chemo tactic, anti-inflammatory, anti-microbial, maintenance of cytokine levels
3. Proliferation
mitogenic to fibroblasts and keratinocytes, pro-angiogenic
4. Remodeling
rearrangement of collagen, regeneration
Tissue engineering
applies the principles of engineering and the life science toward the development of biological substitutes that restore, maintain or improve tissue function
R. Langer& J.P. Vacanti, Science 260:920 (1993)
life sciences
- cell/tissue
- developmental biology
- molecular & cell biology
- transplantation surgery
engineering
- biomaterials
- biomechanics
- bioinstrumentation
- bioimaging
aim of TS
understanding the principles of tissue growth and applying this to produce functional replacement tissue for clinical use
MacArthur and Oreffo, Nature (2005) 433, 19
growth and metabolism -> differentiation -> reeproduction
Growth factor and cytokines
proliferation -> differentiation -> apoptosis
TS triangle
Effects of biomaterial
on tissue
- accommodates tissue attachment
- promotes tissue formation
- affects tissue remodeling (degradation followed by formation)
on cells
- cell attachment
- cell proliferation
- production of matrix molecules and enzymes
- migration
Biomaterial: present and future direction
proactive biomaterials: elicit specific, desired and timely responses from surrounding cells and tissues
PROTEINS
interactions between amino acids are governed by hydrogen, ionic, covalent bonding and hydrophobic interactions
- the primary structure of a protein is its linear sequence of amino acids
- secondary structure refers to localized coiling and bending of the polypeptidechain
- tertiary structure refers to the overall folding of an entire protein subunit
- quaternary structure refers to association of multiple subunits, which maybe identical or each may have its own primary, secondary, and tertiary structure
proteins are chains of amino acids, whose side groups can be nonpolar, polar or charge
the properties and functions of proteins, are directly related to the intramolecular interactions resulting from their primary structures
Factors control protein adsorption
- external parameters: temperature, pH, ionic strengh and buffer composition
- protein properties (hydrophilicity/hydrophobicity, size/shape, charge, structural stability/rigidity)
- surface properties (hydrophilicity, hydrophobicity, charge, topography, chemistry)
Isoelectric point (pI)
when the pH=pI, the net charge of protein is zero, lack of identical electric charge repel force, the solubility of protein is minimum, and the proteins are likely to principate
pH<pI => OH- in and H+ out
and reverse
SUMMARY
- The interaction of proteins with biomaterials is determined by the properties of both the biomolecules and substrate
- Protein factors that effect their interactions with biomaterials include size, charge and structural stability
- Surface factors that influence their interaction with proteins include topography (địa hình), charge, chemical composition and microstructure
- The rate of arrival of protein molecules at a biomaterials surface also plays a significant role in determining adsorption
- The multiple states in which proteins exist on surfaces result from effects of orientation, geometric availability of surface area, and conformational (cấu trúc) changes
- All protein-surface bonds must be simultaneously (đồng thời) broken for a protein molecule to desorb
- The longer a protein molecule resides on a surface, the less likely it is to be desorbed or exchanged by other molecules
- In multicomponent solutions, such as real body fluids, proteins compete for surface binding sites, resulting in a series of collision (va chạm), adsorption and exchange processes on the biomaterials surface
adsorption in surface : hấp phụ
absorption in deeper: hấp thụ
PROTEIN ADSORPTION
Why do protein adsorb?
Nature of side chains presented on the protein surface
Protein’s marginal structural stability
Why the structure of protein can change ???
Binding to ligands or cofactors: Many proteins function by binding to specific ligands, cofactors, or substrates. This binding can induce conformational changes in the protein, which are essential for its function. For example, enzymes often change their structure upon substrate binding to facilitate chemical reactions.
Aggregation: Proteins can aggregate or form complexes with other proteins. This can lead to changes in protein structure and function, and it is associated with various diseases, such as neurodegenerative disorders like Alzheimer's disease.
Post-translational modifications: Proteins can undergo various post-translational modifications, such as phosphorylation, glycosylation, acetylation, or methylation. These modifications can alter the protein's structure, stability, and function.
Mutations: Mutations in a gene that encodes a protein can lead to changes in the amino acid sequence of the protein. These changes can alter the protein's structure and function. Some mutations can result in misfolded or non-functional proteins.
Folding and Unfolding: Proteins are not static; they can undergo reversible conformational changes, folding into their native structure or adopting alternative conformations. This folding and unfolding can be influenced by changes in the cellular environment, such as changes in temperature, pH, or the presence of binding partners.
Environmental factors: Environmental factors, such as changes in temperature, pressure, or solvent conditions, can influence protein structure. Extreme conditions can lead to protein denaturation or structural changes.
Denaturation: Denaturation is a process in which a protein's native structure is disrupted, causing it to unfold or lose its functional shape. This can be caused by changes in temperature, pH, or exposure to chemicals or denaturing agents like urea or guanidine hydrochloride.
Chaperone proteins: Cells have chaperone proteins that assist in the proper folding and stabilization of other proteins. These chaperones can help proteins fold correctly or refold misfolded proteins.