Innovative Polymers for Biomedical Use – Polyurethanes, TPUs & SIBS

Overview of Session

• Date: 29.04.2025
• Lecturer: Lorenza Draghi
• Course: Biomaterials – Politecnico di Milano
• Agenda of the day
  • Innovative polymers (focus)
  • Polyurethanes
  • TPUs
  • SIBS
  • Exercise section
  • Review previous exercise
  • New exercise assignment

Polyurethanes (PU)

• Very large polymer family produced by condensation of polyols (alcohols with $\ge 2\;OH$ per molecule) and poly-isocyanates (molecules with $\ge 2\;NCO$ groups).
• Enormous versatility comes from freedom to choose:
  • Type of di-/poly-isocyanate
  • Type of polyol
  • Additives, co-reactants, catalysts, blowing agents
• Not the newest polymer class but already widely used – still “innovative” through new formulations.

Main Commercial Classes & Examples

• Flexible foams (open-cell) – furniture, mattresses, car interiors.
• Rigid foams (closed-cell) – insulation panels, refrigeration.
• Elastomers – wheels, rollers, medical devices, elastic fibers.
• TPUs – thermoplastic polyurethanes (focus of lecture).
• Coatings & adhesives.

Thermoplastic Polyurethanes (TPU)

• Minority of PU family (most PU are thermosets) yet the most attractive for medical applications.
• Block-copolymer (segmented) structure: alternating hard segments (HS) and soft segments (SS).
  • HS ≈ di-isocyanate + short-chain diol (chain-extender).
  • SS ≈ long-chain macro-diol.
• Microphase separation → semi-crystalline HS domains (5–10 nm wide, 40–100 nm long) dispersed in amorphous SS matrix.
  • HS domains act as physical cross-links => reversible under heat/pressure (thermoplastic behavior).
• Tuning variables
  • HS/SS ratio
  • Chemical nature + molar mass of each component
  • Processing conditions (temperature, solvents, catalysts).

Thermal / Dynamic Mechanical Behavior

• Miscibility assessment via $tan\,\delta$:
  • Poor miscibility ⇒ double $T_g$ peaks (one per phase).
  • Good miscibility ⇒ single broad peak located between $T<em>{g,HS}$ and $T</em>{g,SS}$.
• Mechanical design rule-of-thumb
  • ↑ HS content ⇒ ↑ modulus & strength, ↓ elongation at break.
  • ↑ SS content ⇒ opposite effects.

Generic Biomedical Merits

• Excellent flex-fatigue resistance.
• Good biocompatibility & hemocompatibility.
• Chemical resistance (acids, bases, many organics).
• Low bacterial adhesion.

Typical Medical Uses (non-exhaustive)

• Blood bags, closures, fittings.
• Oxygenator tubing.
• Cardiac-assist pump bladders / housings.
• Variety of catheters & endotracheal tubes.
• Hemodialysis membranes & connectors.
• Pacemaker components (lead insulation, fixation).
• Vascular grafts & patches.
• Skin dressings, surgical tapes / drapes.
• Orthopedic splints, bone adhesives.
• Condoms, vaginal sponges, breast implants, dental chains, bone cements, tissue-engineering scaffolds.

TPU Synthesis Routes

(1) One-Shot / Single-Stage (Bulk, no solvent)

• All three components (macro-diol + di-isocyanate + chain-extender) mixed simultaneously.
• Features
  • Random HS/SS distribution ⇒ less control.
  • Cost-effective; typical for foams.
• Lab setup: mechanical stirrer until viscosity rises, then poured in molds for post-curing.
• Industrial example: FOAM-IT!™ rigid PU foams (3–26 lb/ft³ densities; water-blown; self-skinning variants, long/short pot-life grades).

(2) Two-Stage (Prepolymer route)

• Step 1: Macro-diol + excess di-isocyanate → $\text{OCN-PREPOLYMER-NCO}$.
• Step 2: Chain-extender added (often in solvent) → alternated HS/SS sequence.
• Precipitation in a non-solvent (water) followed by isolation & purification.
• Advantages: tighter stoichiometric control, minimized free di-isocyanate (critical for medical use).

Stoichiometric Notes

• Ratios of $NCO:OH$ (and other functionalities) must avoid residual toxic di-isocyanate.
• Variation of stoichiometry adjusts HS/SS content & final viscosity.

Designing Medical TPUs – Component Choices

Macro-Diol (Soft Segment)

• Polyester-diol ⇒ good flexibility + toughness but hydrolytically sensitive (first-generation).
  • By selecting biodegradable polyesters one can purposely create bio-degradable TPUs for tissue engineering.
• Polyether-diol ⇒ hydrolytically stable; yet susceptible to oxidative surface cracking (ESC).
  • Example: Tecoflex® (aliphatic polyether-urethane).
  • Reactive oxygen species from macrophages/FBGC thought to initiate oxidation.
• Polycarbonate-diol ⇒ superior oxidative stability; however may undergo enzymatic attack.
  • Basis for PCU (poly-carbonate-urethane) spinal stabilizer spacers.

Di-Isocyanate (Hard Segment)

• First-generation used aromatic di-isocyanates (e.g.
  $MDI, TDI$) → toxic degradation by-products.
• Shift to aliphatic di-isocyanates (e.g.
  $HMDI, HDI$) for in vivo safety.

Chain-Extender

• Short, symmetric diols / diamines create ordered HS.
• Diamines form ureic linkages >> stronger H-bond network vs urethane linkages.

Additives

• Catalysts – accelerate reaction.
• Blowing agents – tailor porosity (foams).
• Stabilizers, pigments, processing aids (multiple generations of formulations).

Failure Modes & Case Studies

Polyether-Urethane (Tecoflex®)

• O2-mediated surface cracking & deep crazing (ESC).
• ESR/ATR-FTIR confirm oxidation + chain scission.

Polycarbonate-Urethane (PCU) Spinal Stabilizers

• Construct: pedicle screws + hollow PCU spacers + PET cable.
• In vitro: abrasion marks, micro-cracks, ATR-FTIR evidence of oxidation.
• Explant (vascular graft mesh) after 2 years: surface cracking of 10 µm PCU fibers.

Silicone-Containing TPU (TSPU / PUR-Sil™)

• Macro-diol of polysiloxane type combined with conventional TPU hard segments.
• Aims to merge advantages:
  • From TPU → thermoplastic processability, toughness, tear resistance.
  • From silicone → hydrolytic stability, high hydrophobicity, thrombo-resistance, thermal stability.
• Trade-offs illustrated by graph: tensile strength ↓ and relative biostability ↑ with increasing wt % silicone.
  • Need to optimize silicone content (typically 10–40 wt %) to balance strength vs longevity vs cost.

SIBS (Polystyrene-Isobutylene-Polystyrene)

Rationale & Chemistry

• Developed to overcome long-term oxidative/hydrolytic degradation & inflammation seen with PU.
• Design guideline: main chain + pendant groups should lack sites prone to oxidation, hydrolysis, enzymatic cleavage.
  • Ideal backbone: alternating secondary & quaternary carbons.
• Polyisobutylene (PIB) satisfies chemistry but is non-crosslinkable → unusable alone.
• Solution: triblock thermoplastic elastomer – soft PIB mid-block, hard PS end-blocks.
  • Physically cross-linked (microphase separated).
• Synthesis – living carbocationic polymerization; $M_w$ & PS mol % controlled via monomer/initiator ratio.

Properties

• Combination of silicone-like & PU-like traits:
  • Thermoplastic, solvent-soluble (enables dip/spray coatings).
  • Highly resistant to oxidation/hydrolysis; excellent flex-fatigue.
  • Very good hemocompatibility & general biocompatibility.
• Tunable hardness: higher styrene → higher Shore hardness (see mol% styrene vs hardness graph).
• Limitations:
  • Stress-cracking in some organic solvents.
  • Susceptible to creep (needs reinforcement for load-bearing).
  • No hydrogen-bonding sites → lower tensile strength vs TPU.
  • Low gas permeability → difficult EtO sterilization; cannot be γ-irradiated.
  • Higher synthesis/purification cost.

Biomedical Applications & Evidence

• Ophthalmology devices, stent-grafts, drug-eluting stents (DES), synthetic tricusp aortic valves.
• TAXUS® coronary DES: SIBS coating releases Paclitaxel.
  • Comparative in vivo study: PCU showed greater PMN infiltration than SIBS → lower inflammation with SIBS.
• Valve project: low-modulus SIBS (7–9 mol% styrene) fabric-reinforced leaflet + high-modulus SIBS (35–40 mol%) frame.
  • Promising in vivo; reduced calcification, embrittlement, degradation.
• Stability studies: SIBS microfibers after 6 months & 2 years show no surface degradation (SEM).

Comparative Summary & Design Guidelines

• Thermoplastic biomedical elastomers can be engineered along HS/SS architecture:
  • Polyurethane family (TPU) – Greatest property tunability, but watch for oxidative/hydrolytic degradation depending on soft-segment chemistry.
  • TPU-silicone hybrids – same processability, boosted hydrolytic stability; mechanical properties drop with excess silicone.
  • SIBS – Oxidative/hydrolytic inertness & superior flex-fatigue; mechanical reinforcement or design needed to mitigate creep & solvent cracking.
• Choice depends on:
  • Target mechanical load (tension vs flexion) and fatigue regime.
  • Required life span (temporary vs permanent implant).
  • Type of body fluid exposure (blood contact, oxidative cells).
  • Sterilization constraints, cost limits, drug-release needs.

Practical / Ethical / Regulatory Notes

• Residual di-isocyanate in TPU must be minimized for cytotoxicity reasons → analytical verification mandatory.
• First-generation aromatic isocyanates limited due to carcinogenic metabolites – regulators favor aliphatic variants.
• Degradable TPUs open possibilities for resorbable scaffolds but rate must match tissue regeneration → design via macro-diol chemistry.
• SIBS manufacturing purity crucial (low leachables/extractables) to satisfy ISO 10993.
• Environmental impact: shift toward solvent-free processes (one-shot bulk) vs solvent routes; yet medical grade often still relies on solvent/precipitation for purity control.

Formulae & Key Chemical Groups (for reference)

• Urethane linkage: $R<em>1\,NH\,CO\,O\,R</em>2$
• Urea linkage (from diamine extender): $R<em>1\,NH\,CO\,NH\,R</em>2$
• Hard segment repeat (simplified): $\bigl[\,OCN\,R<em>{iso}\,NCO + HO\,R</em>{ext}\,OH\,\bigr]$
• Soft segment (polyester example): $HO\,(\;O\,C\,R<em>{co}\,O\,R</em>{poly}\,)_n\,OH$
• Stoichiometry requirement: $NCO<em>{tot} \approx OH</em>{tot}$ to avoid free $NCO$.