Natural and Semi-Synthetic Polymers

Types of Natural Polymers
- Polypeptides (Proteins)
  - Basic unit: Amino acid
  - Connection: Peptide bond
- Polysaccharides (Sugars)
- Polynucleotides (DNA/RNA)
  - Basic unit: Nucleotide
    - Structure includes:
      - Base
      - Phosphate
      - Sugar (e.g., Glucose)
Molecular structures of amino acids and nucleotides depicted.

Types of Polymers and Sources:
- Collagen/Gelatin
  - Source: Rat tail, found in most tissues
- Matrigel
  - Source: Tumor matrix (basal lamina)
- Fibrinogen/Fibrin
  - Source: Plasma (part of blood clotting)
- Silk fibroin
  - Source: Silk worm cocoons
- Hyaluronic acid
- Chitosan
  - Source: Lobster, crab, and shrimp shells
- Alginate
  - Source: Brown algae
- Methylcellulose
  - Source: Bacteria, tunicates, plants
Clinical Applications:
- Collagen: Skin grafts, cardiac patches, corneas
- Matrigel: 3D models, experimental cell therapies
- Fibrinogen/Fibrin: Hemostasis and adhesion
- Silk Fibroin: Suture, surgical mesh
- Hyaluronic Acid: Anti-adhesive films, wound dressing
- Chitosan: Drug release tablets

Modification of Biopolymers to Biomaterials:
- Natural polymers are typically free-floating (e.g., proteins) and require crosslinking to attain solid form.
- Exceptions: Some polysaccharides like chitin/chitosan and methylcellulose exhibit intermolecular binding without additional crosslinking.

Types of Crosslinks:
- Hydrogen Bonding:
  - Semi-reversible; exhibit limited stability.
- Chemical Crosslink:
  - Permanent; typically stable under proper conditions.
- Physical Crosslink:
  - Reversible; formed via noncovalent bonds.
- Ionic Crosslink:
  - May be covalent or noncovalent; often permanent and reliably stable.

Physical Features:
- Fibrous proteins, e.g., collagen, undergo physical crosslinking.
- Collagen fibers physically entangle and bond together, creating 2 μm structures and substructures as small as 500 nm.

Formation Process:
- Three collagen molecules bind to form a triple helix (coiled coil).
- Hydrogen bonds play a crucial role in stabilizing the structure.
- Crosslinking occurs within approximately 30 minutes at body temperature.
- Fibrillogenesis: Process by which collagen twists into helical fibrils that are stacked into fibers.
  - Sensitive to temperature, requiring controlled environments for optimal structure formation.

Definition: Solubilized, amorphous form of collagen I; derived from fish scales and animal bones.
Properties:
- Acts similarly to a thermoset material.
- Distinction between collagen (ordered protein backbone) and gelatin (disordered protein backbone) made evident upon heating.

Polysaccharides are less structured, appearing more amorphous compared to proteins.
Matrix Phase: If tissue is a composite material, polysaccharides contribute to this matrix phase.

List of common biopolymers:
- Proteins: Elastin, Fibrinogen and fibrin, Silk protein, Hyaluronic acid, Alginate, Chitin, Agarose, Cellulose.
Synthesis:
- Small fragments can often be synthesized in laboratories, but full-length versions are slow and costly, necessitating sourcing from natural sources or engineered bacteria.

Description: Amorphous polypeptide with covalent crosslinks, functioning as an elastomer.
Production: Secreted as monomers, then crosslinked by enzymes to form larger structures.

Function: Primary structural component of blood clots, initially liquid until reacting with thrombin to form a fibrous matrix.

Source: Isolated from silk worm cocoons.
Structure: Peptide fibers stack via hydrogen bonding; formation can involve both hydrophilic and hydrophobic interactions.
Main Components: N-terminus and C-terminus, linked with disulfide bonds (involving heavy and light chains).

Description: Repeating disaccharide isolated from seaweed or bacteria.
Characteristics: Generally present in low concentration in tissues, particularly neural and cartilage.
Properties: Non-adhesive for adult cells while retaining water content.

Definition: Disaccharide derived from algae.
Crosslinking: Ionic crosslinking with calcium, forming a unique “egg box” model; intermolecular crosslinks vulnerable to disruption by calcium chelation.

Source Characteristics: Available from plants and animals, pursued as bioplastic alternatives.
Functionality: Capable of sequestering growth factors for drug loading and other applications.

Certain polysaccharides (e.g., agarose) can form stable crosslinks upon cooling, described as thermoplastics.
Reversible bonding allows properties such as self-healing capabilities.

Mammalian vs Non-Mammalian Sources:
- Polysaccharides from plant sources are biocompatible but not fully recognized by the body.
- Generally non-adhesive and non-immunogenic; valuable for infection prevention and cell clustering.
- Not typically suitable for cell adhesion, ingrowth, or remodeling applications.

Definition: Biopolymers modified for enhanced properties such as chemical crosslinking.
Functional Groups: Chemical groups like alcohol (–OH) or carboxylic acids (–COOH) exhibit reactive properties for adding new functionalities.

Chemical Crosslinks:
- Amide (peptide) bonds: Strong and irreversible.
- Photo-crosslinks: Induced by light, usually irreversible.
- Disulfide (thiol) bonds: Reversible through oxidation.
Physical Crosslinks:
- Formed through hydrogen bonding or ionic interactions.

Examples of crosslinking by chemical means:
- Gelatin functionalized for amide (peptide) bonding.
- Methacrylated Hyaluronan that crosslinks under UV light.
Reversible Chemical Crosslinking: Occurs due to disulfide bridges, notably in sulfur-modified or thiolated hyaluronan, as well as peptide materials rich in cysteines for disulfide bonding under neutral conditions.