MAR 23, 202656 MINS READ
Polycaprolactone is defined by its linear aliphatic polyester backbone, with the repeating unit formula —(CO—O—CH₂—CH₂—CH₂—CH₂—CH₂—)ₙ— 2,5,16. This structure arises from the ring-opening polymerization of ε-caprolactone, a seven-membered cyclic ester, under catalysis by metal-organic compounds such as tetraphenyltin or coordination catalysts 2,5. The polymer's semi-crystalline nature (crystallinity typically 40–50% 6) results from the regular packing of methylene sequences, while the ester linkages introduce polarity and sites for hydrolytic degradation 10,16.
Key Structural Features:
Functional Group Modifications:
Recent advances have introduced multifunctionalized PCL variants bearing amino, hydroxyl, or epoxy groups 3,12. For example, multifunctionalized bioactive PCL with at least two amino groups per chain has been synthesized to enhance cell adhesion and bioactivity 3. Similarly, carboxyl-terminated PCL prepared via reaction with anhydrides enables conjugation with fluorinated acrylate polymers for hydrophobic surface modification 2. Hydroxyl-terminated PCL precursors are also reacted with fumaric acid to yield polycaprolactone fumarate (PCLF), a cross-linkable derivative suitable for nerve conduits and bone scaffolds 12.
Ring-opening polymerization (ROP) of ε-caprolactone is the dominant industrial route, offering superior control over molecular weight and minimizing side reactions compared to polycondensation of 6-hydroxycaproic acid 5. ROP proceeds via anionic, cationic, or coordination mechanisms, with coordination catalysts (e.g., tin(II) octoate, aluminum alkoxides) being most prevalent due to their high activity and tolerance to functional groups 5,14.
Catalyst Selection And Performance:
Process Conditions:
Typical bulk ROP is conducted at 150–180°C under inert atmosphere (nitrogen or argon) to prevent oxidative degradation 1,5. Reaction times range from 2 to 6 hours, with catalyst loadings of 0.1–0.5 wt% relative to monomer 5,14. Post-polymerization, residual monomer is removed by vacuum stripping, and the polymer is pelletized for downstream processing 1.
PCL is frequently copolymerized with other lactones or lactides to tailor degradation kinetics and mechanical properties:
PCL's mechanical profile is characterized by moderate tensile strength, high elongation at break, and low modulus, making it suitable for flexible biomedical devices:
PCL is soluble in a wide range of organic solvents, including chloroform, dichloromethane, tetrahydrofuran, and hexafluoro-2-propanol (HFIP), facilitating solution-based fabrication techniques such as electrospinning, solvent casting, and nanoprecipitation 2,10,18. Its low melting point enables melt extrusion, injection molding, and 3D printing at temperatures below 100°C, minimizing thermal degradation and energy consumption 1,4,10.
Melt Viscosity: At 150°C, PCL melt viscosity ranges from 500 to 2,000 Pa·s (at shear rates of 10–100 s⁻¹), depending on molecular weight 1. Addition of plasticizers (e.g., glycerin, sorbitol) reduces viscosity and improves film-blowing processability 1.
PCL undergoes hydrolytic degradation via random scission of ester bonds, yielding ε-hydroxycaproic acid oligomers that are metabolized via the tricarboxylic acid cycle or excreted renally 10,12. Degradation is autocatalytic, accelerated by acidic byproducts, and proceeds more slowly than poly(lactic-co-glycolic acid) (PLGA) due to PCL's hydrophobicity and high crystallinity 4,10.
Degradation Rates:
Acidification Concerns: PLGA degradation generates lactic and glycolic acid, causing local pH drops (pH 4–5) that induce inflammation and cytotoxicity 8. PCL's slower degradation mitigates acidification, but copolymers with glycolide may still require buffering agents (e.g., magnesium hydroxide) to neutralize acidic byproducts 8.
PCL's biocompatibility, tunable degradation, and processability make it a leading scaffold material for bone, cartilage, nerve, and vascular tissue engineering 4,10,12,15.
Bone Regeneration:
PCL scaffolds are often mineralized with hydroxyapatite or coated with polydopamine to enhance osteoconductivity 4. For example, PCL-pDA-pMAA (polymethacrylic acid) composites exhibit bone-like apatite formation in simulated body fluid (SBF) within 7 days, with compressive moduli of 50–100 MPa 4. Three-dimensional printed PCL scaffolds with 60% porosity and 400 μm pore size support osteoblast proliferation and differentiation, achieving bone ingrowth of 40–60% in rabbit femoral defects over 12 weeks 4,10.
Nerve Conduits:
Polycaprolactone fumarate (PCLF) nerve conduits (inner diameter 1.5 mm, wall thickness 0.5 mm) support robust axonal regeneration across 10 mm rat sciatic nerve defects, with nerve conduction velocities recovering to 70–80% of normal by 12 weeks post-implantation 12. PCLF's cross-linkable nature allows in situ curing and mechanical matching to native nerve tissue (tensile modulus 5–10 MPa) 12.
Cartilage Repair:
Electrospun PCL nanofibers (diameter 200–800 nm) seeded with chondrocytes and cultured in chondrogenic medium produce cartilage-like extracellular matrix with glycosaminoglycan content of 15–25 μg/mg scaffold and collagen type II expression comparable to native cartilage 8,10. Addition of magnesium hydroxide (5–10 wt%) neutralizes acidic degradation products, maintaining pH 7.0–7.4 and reducing cytotoxicity 8.
Vascular Grafts:
PCL-PEG-PCL triblock copolymer tubes (inner diameter 4 mm, wall thickness 0.8 mm) exhibit burst pressures of 1,500–2,000 mmHg and suture retention strengths of 2–3 N, meeting requirements for small-diameter vascular grafts 6. PEG segments reduce platelet adhesion and thrombosis, with patency rates of 60–70% in rat aortic interposition models over 8 weeks 6.
PCL nanoparticles, micelles, and films enable sustained release of hydrophobic and hydrophilic drugs over weeks to months 10,18,19.
Nanoparticle Formulations:
PCL nanoparticles (diameter 100–300 nm) prepared by nanoprecipitation encapsulate chemotherapeutics (e.g., docetaxel, camptothecin, etoposide) with loading efficiencies of 60–80% and release 50–70% of payload over 30 days in vitro 18. PEGylation of PCL nanoparticles increases circulation half-life from 2–4 hours to 12–24 hours in mice, enhancing tumor accumulation via the enhanced permeability and retention (EPR) effect 19.
Electrospun Meshes:
Poly(lactic acid-co-caprolactone) (90:10 molar ratio) electrospun meshes loaded with anti-inflammatory (e.g., 5-aminosalicylic acid) or antimicrobial agents (e.g., silver nanoparticles) release 40–60% of drug over 14 days, with zero-order kinetics suitable for wound dressings and post-surgical adhesion prevention 11,18.
Implantable Depots:
PCL rods (diameter 3 mm, length 10 mm) containing aripiprazole (antipsychotic) or isradipine (antihypertensive) provide steady-state plasma concentrations for 3–6 months in rats, reducing dosing frequency and improving patient compliance 18.
PCL's biodegradability and compatibility with conventional plastics enable its use in compostable films, adhesives, and coatings 1,13,16.
Biodegradable Films:
PCL blended with modified starch (oxidized or hydroxypropyl starch, 20–40 wt%) and poly(succinic acid-adipic acid-butanediol) copolyester (20–40 wt%) yields films with tensile strength of 25–35 MPa, elongation at break of 400–600%, and water vapor transmission rates (WVTR) of 50–80 g/m²/day, suitable for food packaging 1. Addition of waterproofing agents (e.g., beeswax, epoxidized soybean oil, 5–10 wt%) reduces WVTR to 20–40 g/m²/day 13.
Home Compostable Blends:
PCL (30–50 wt%) blended with polyglycolic acid (PGA, 30–50 wt%) and polyhydroxyalkanoates (PHA, 10–20 wt%) disintegrates in home compost (25–30°C, 60% humidity) within 90–120 days
| Org | Application Scenarios | Product/Project | Technical Outcomes |
|---|---|---|---|
| NANJING WURUI BIODEGRADABLE NEW MATERIAL RESEARCH INSTITUTE CO. LTD. | Biodegradable packaging films for food applications requiring good mechanical strength, water resistance, and compostability. | PCL Modified Starch-Based Biodegradable Resin | Blending PCL with poly(succinic acid-adipic acid-butanediol) copolyester and modified starch achieves tensile strength of 25-35 MPa, elongation at break of 400-600%, and film-blowing at 150-178°C with improved mechanical performance and water resistance. |
| UNIVERSIDADE DO MINHO | Bone regeneration scaffolds, injectable bone adhesives, and implants requiring osteoconductivity and mechanical matching to native bone tissue. | PCL-pDA-pMAA Bone Adhesive | Polycaprolactone coated with polydopamine and polymethacrylic acid exhibits bone-like apatite formation in simulated body fluid within 7 days, compressive moduli of 50-100 MPa, and enhanced biomineralization promoting bone-bonding. |
| Mayo Foundation for Medical Education and Research | Peripheral nerve repair, segmental nerve defect reconstruction, and tissue engineering applications requiring cross-linkable, biocompatible scaffolds with controlled degradation. | Polycaprolactone Fumarate (PCLF) Nerve Conduits | PCLF nerve conduits (1.5 mm inner diameter, 0.5 mm wall thickness) support robust axonal regeneration across 10 mm rat sciatic nerve defects with nerve conduction velocities recovering to 70-80% of normal by 12 weeks, releasing no diethylene glycol during degradation. |
| Changzhou University | Industrial-scale production of high-molecular-weight polycaprolactone for biomedical applications, drug delivery systems, and tissue engineering scaffolds requiring low-toxicity synthesis routes. | Zinc-Containing Isopoly-Molybdic Acid MOF Catalyst | Novel metal-organic framework catalyst enables bulk ring-opening polymerization of ε-caprolactone without alcohol initiators, achieving weight-average molecular weights exceeding 50,000 g/mol with high thermal stability, reproducibility, and reduced cytotoxicity compared to organotin catalysts. |
| BASF SE | Sustainable packaging materials, compostable films, and single-use products requiring home compostability, biodegradability, and compatibility with conventional plastic processing equipment. | PCL-PGA-PHA Home Compostable Blend | Blending polycaprolactone (30-50 wt%) with polyglycolic acid (30-50 wt%) and polyhydroxyalkanoates (10-20 wt%) achieves complete disintegration in home compost (25-30°C, 60% humidity) within 90-120 days while maintaining mechanical integrity during use. |