Materials

Fig. 4 Representation of co-polymer using two different monomers

The full range of copolymers of lactic acid and glycolic acid has been investigated. The two main series are those of LA/ GA and (DL) LA/GA. It has been shown that composition in the 25 to 75% range for (L) LA/GA and 0 to 70% for the (DL) LA/GA are amorphous. For the (L) LA/GA copolymers, resistance to hydrolysis is more pronounced at either end of the copolymers compositions range. The 70/30 LA/GA has the highest water uptake, hence the most readily degradable in the series. In another study it has been shown that the 50/ 50 copolymer was the most unstable with respect to hydrolysis.

However, it is generally accepted that intermediate copolymers are very much more unstable than the homopolymers. The first commercial use of this copolymer range was the suture material vicryl ((L) LA/GA=10:90). The application of ((DL) LA/GA) copolymer has been in the field of controlled drug release.

Polymer Degradation

Degradation characteristics depend not only on compolymer ratios but also on microstructure, molecular structure processing conditions, shape of the implant, and implantation site.

The microstructure of a polymer refers to whether it is amorphous or crystalline (Fig.5). An amorphous structure means that the polymer chains are randomly oriented. The chains are lossely packed and can slip past each other relatively easily. Crystalline polymers have regions in which the chains lie parallel and in close proximity to each other. Fig. 5 Polymer micro structures, Amorphous (left), and semi crystalline (right) regions.

Homopolymer chains tend to form more ordered structures which are therefore more crystalline Copolymers tend to form less ordered structures which are therefore usually amorphous. However, even crystalline homopolymers are never completely crystalline. Further a crystalline polymer will always contain both crystalline and amorphous regions and is best termed semi-crystalline (Fig 5).

Crystalline polymers have a regular internal structure and because of the orderly arrangement are slow to degrade. Amorphous polymers have a random structure and completely and more easily degraded. Semicrystalline polymers have crystalline and amorphous regions. Breakdown of the implant begins in the amorphous area leaving the more slowly degrading crystalline debris.

During the first phase of degradation water penetrates the biodegradable device, initially cutting the chemical bonds and converting the long polymer chains into shorter and shorter fragments (hydrolysis).

In the second phase, the fragments are degraded into natural monomeric acid found in the body, such as lactic acid. These acids enter the Kreb’s (citric acid) cycle and metabolized into carbon dioxide and water which are then exhaled and excreted in phase three.

Fig.6 illustrates the degradation process of a biodegradable polymer. The polymer PLLA and PGA exhibit distinctly different degradation behaviour. PGA is hydrophilic and degrades very quickly, losing virtually all strength within one month and all mass within 6-12 months. During this phase of rapid degradation large quantities of Glycolide monomer are released.

Fig. 6 Degradable process of a biodegradable polymers

PLLA has a much slower rate of absorption. This homopolymer of L lactide is highly crystalline due to the ordered pattern of the monomers and has been documented to take more than 5 years to absorb.

Bio-degradable implants do induce a non-symptomatic but histopathologically recognizable tissue response, it seems to be a phenomenon inherent in the degradation and absorption processes. This is expected and normal as long as it does not cause any clinical signs.

However, incidence of adverse tissue reaction to implants made of PGA (faster degradation) has been reported from 2.0 to 46.7%. Adverse reactions can occur if the rate of degradation exceeds the limit of tissue tolerance. Local accumulation or released monomers may lower the local PH of the tissue. This drop in the local PH in turn can lead to increased osmotic pressure which may lead to a temporary expansion of the implant cavity or to a local sterile fluid

accumulation. The patient would notice this reaction as swelling and pain and would typically be prescribed anti inflammatory drugs and rest. Conversely in studies investigation PLA – based implants (slower degradation) the incidence of adverse tissue reaction is much lower from 0 to 1%.

IDEAL BIODEGRADABLE MATERIALS

The ideal biodegradable material provides appropriate strength while degrading in a predictable fashion throughout the healing process, without causing adverse reactions. The material of Inion OPTIMATM live upto this ideal. The polymers of OPTIMA library of blends get thing physical properties from varying proportions or its composite monomers.

• L – Lactide
  - provide strength to implant
  - Hydrophobic – degrades slowly
• D Lactide
  - Disrupts crystallinity
  - Flexibility
• Glycolide
  - Hydrophilic – degrades quickly
• TMC (PGA/Tri-methylene Carbonate)
  - Glass transition temperature is subzero, it is rubbery at room  temperature
  - Provides enhance malleability and toughness

Because these materials consists of several monomer types, they are amorphous and degrade completely. The implants also remain amorphous after manufacturing due to Inion’s carefully controlled production processes. (some other copolymers become semi-crystalline during manufacture) In comparing the degradation of Inion OPTIMATM to PLLA and PGA : PLLA degrades slowly with crystalline debris usually remaining. PGA degrades completely but too quickly. OPTIMATM degrade completely and within the appropriate length at time for each applications (Fig.7).

Fig. 7 Mass loss rate of fast degrading PGA-co-PLA 90/10 copolymer and slowly degrading crystalline PLLA in comparison to Inion OPTSTM 2.0 mm plate material.

Tailored degradation

The tailored degradation rate of the material progressively transfer load to healing tissue so that the material degrades coincide with the rate of tissue healing (Fig.8)

Fig. 8 The material’s mechanical properties decrease as it degrades.

CONCLUSION

Properly designed biodegradable implant often clear advantages over the traditional/conventional/routinely used implants. They retain their strength long enough to support a healing tissue then gradually and harmlessly disintegrate in the patient’s body.

References:-

1. K.P.Andriano, T.Pohjonen and P.Tormala, Processing and characterization of absorbable polylactide polymer for use in surgical implants. J.Appl.Biomater; 5 (2) 133-40, 1994.

2. O.Böstman and H.Pihlaja mä ki, Clinical biocompatibility of biodegradable orthopaedic implants for internal fixation, a review, Biomaterial 21, 2615, 2000.

3. J.C.Middleton and A.J.Tiptone, Synthetic bio-degradable polymers as orthopaedic devices, Biomaterials, 21, 2335, 2000.

4. M.Vert, P.Christel, F.Chabot, J.Lerary and G.W.Hastlings, P.Ducheyne, Macrololecular Biomaterials, CRC Press, Boca Raton, eds. (1984) p.119.

5. D.F.William and E.Mort Enzyme-accelerated hydrolysis of polyglycolic acid. J.Bioleng 1,231 (1977).