Biodegradable Polymeric Biomaterial

Presented by: Ikhwan Hidayat ( 이흐완 히다얏 )

Contents Introduction & Application Poly (α-esters)

Polyglycolide (PGA) Polylactide (PLA) Polycaprolactone

Other Polymers under Development Biodegradation Mechanism Packaging & Sterilization Surface Modification for Biodegradable Polymer

Introduction

The current trend, Biodegradable are more favorable than biostable material for biomedical applications.

Important properties of a biodegradable polymer: Appropriate mechanical properties. Does not evoke inflame or toxic response. Have acceptable shelf life. Degradation time should match the healing. Fully metabolized & Easily sterilized.

Classifications Hydrolytically & Enzymatically degradable

Applications

Large Implants: Orthopedic fixation devices; bone screws , bone plates

Small implants: Sutures, Staples, Nano/Micro-sized drug delivery

Dental devices: as a void filler and as a guided-tissue-regeneration (GTR)

Multifilament meshes or porous structures for tissue engineering

Figure 1. Biodegradable intravascular stent

Poly(α-esters) Thermoplastic polymer with hydrolytically labile aliphatic

ester linkages in their backbone. Only short aliphatic chains can degrade over the time required

for biomedical application Good biocompatibility and controllable degradation profiles

Poly(α-esters) based on polylactide (PLA), polyglycolide (PGA), and polycaprolactone (PCL) have been extensively employed as biomaterials.

Figure 2. Polyester based, meniscus repair devices

Polyglycolide (PGA) Highly crystalline polymer

Excellent mechanical properties Excellent fiber forming ability

Initially investigated for developing resorbable sutures DEXON, approved 1960

In the body, PGA are broken down into glycine Excreted or converted

Applications: Scaffolding matrices for tissue regeneration Bone Internal Fixation Devices (Biofix)

Polylactides (PLA) Lactide is a chiral molecule

L-lactide (PLLA) DL-lactide (PDLLA)

PLLA: slow degradation time, crystalline, good tensile strength, low elongation and high modulus Load bearing applications Scaffold for developing ligament replacement

Poly DL-lactide (PDLLA): amorphous, lower strength & higher elongation, rapid degradation time Drug delivery system

Poly(ε-caprolactone) (PCL) Semicrystalline polyester

Highly processible,Low melting point (55-60 oC) &Glass transition temperature (-60 oC)

Low tensile strength but extremely high elongation Slow rate degradation, high permeability to many

drugs and non-toxicity Long-term drug/vaccine delivery devices A copolymer of ε-caprolactone with glycolide, as a

monofilament suture (Monacryl)

Other Polymers under Development Low-cost biodegradable polyemer

Synthesis of polymers using microorganism Polyhydroxybutyrate (PHB) & polyhydroxyvalerate (PHV),

commercially available as a copolymer named Biopol Require enzymes for biodegradation Under consideration for several biomedical application

Synthetic poly(amino acids) Wide occurrence in nature High crystalline: difficult to process and slow degradation Synthesizing “pseudo” poly(amino acids) using tyrosine

derivative

Biodegradation Mechanism

Second phase Enzymatic attack and metabolization

of the fragments occur Resulting in a rapid loss of polymer

mass, this type of degradation is also called “bulk erosion”

Simple chemical hydrolysis of the hydrolytically unstable backbone First phase

Water penetrates the bulk of the device, attacking the chemical bonds

Reduction in molecular weight &the physical properties

Biodegradation Mechanism Surface Erosion

Polymer penetrates the device, slower than the rate of conversion of the polymer into water-soluble materials.

Results in the device thinning over time while maintaining its bulk integrity.

Related factors that resulting degradation: Chemical Stability The presence of catalyst, additives,

impurities. The geometry of the device

Packaging Hydrolytically unstable

the presence of moisture can degrade the biodegradable polymers

The polymers are quickly packaged after manufacture Double-bagged, under an inert atmosphere or vacuum

Final packaging Placing the device in a moisture proof container

Sterilization Biodegradable polymer is sterilized by gamma or E-beam

irradiation or Ethylene Oxide (EtO) gas Temperature and humidity should be considered

“Biomimetic calcium phosphate coating on electrospun- poly(ε-caprolactone) scaffolds for bone tissue engineering”

PCL scaffolds with uniform fibrous structure were fabricated by electrospinning.

Before CaP coating, a plasma surface treatment was applied to clean and activate the PCL surface for calcium and phosphate

ion grafting.

The treated PCL scaffolds were immersed in 10× simulated body fluid (SBF10) for varying time periods.

By: F. Yang, J.G.C. Wolke, J.A. Jansen

The deposited calcium phosphate coatings improved the wettability of the electrospun PCL scaffold.

As the mineralized electrospun scaffold has a similar structure as the natural bone, it is expected to be a

potential cell carrier in bone tissue engineering.

characterization

• Scanning Electron Microscopy (SEM)• Gravimetric measurement• X-ray Diffraction• Energy Dispersive Spectroscopy• Water wettability test

Appendix a. Properties of common biodegradable polymers

Polymer Melting Point (°C) Glass-Transition Temp (°C) Modulus (Gpa)a Degradation Time

(months)b

PGA 225—230 35—40 7.0 6 to 12

PLLA 173—178 60—65 2.7 >24

DLLA Amorphous 55—60 1.9 12 to 16

PCL 58—63 (—65)— (—60) 0.4 >24

PDO N/A (—10)— 0 1.5 6 to 12

PGA-TMC N/A N/A 2.4 6 to 12

85/15 DLPLG Amorphous 50—55 2.0 5 to 6

75/25 DLPLG Amorphous 50—55 2.0 4 to 5

65/35 DLPLG Amorphous 45—50 2.0 3 to 4

50/50 DLPLG Amorphous 45—50 2.0 1 to 2

a Tensile or flexural modulus.

b Time to complete mass loss. Rate also depends on part geometry.

Appendix b. Commercial biodegradable medical products

Application Trade Name Composition a Manufacturer Dexon PGA Davis and Geck

Maxon PGA-TMC Davis and Geck

Vicryl PGA-LPLA EthiconSutures Monocryl PGA-PCL Ethicon PDS PDO Ethicon Polysorb PGA-LPLA U.S. Surgical Biosyn PDO-PGA-TMC U.S. Surgical

PGA Suture PGA Lukens

Sysorb DLPLA Synos Endofix PGA-TMC or LPLA Acufex

Arthrex LPLA ArthrexInterference screws Bioscrew LPLA Linvatec

Phusiline LPLA-DLPLA Phusis Biologically Quiet PGA-DLPLA Instrument Makar

Suture anchor Bio-Statak LPLA Zimmer Suretac PGA-TMC Acufex

Anastomosis clip Lactasorb LPLA Davis and Geck

Anastomosis ring Valtrac PGA Davis and Geck

Dental Drilac DLPLA THM Biomedical

Angioplastic plug Angioseal PGA-DLPLA AHP

Screw SmartScrew LPLA Bionx

Pins and rods Biofix LPLA or PGA Bionx Resor-Pin LPLA-DLPLA Geistlich

Tack SmartTack LPLA BionxPlates, mesh, screws LactoSorb PGA-LPLA Lorenz

감사합니다

Thank you for your attention….

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