BIODEGRADABLE IMPLANTS & MATERIALS new.pptx

biodegradable implants for orthopedic surgeons in day to day clinical practice.for undergraduate and postgraduate learning and for research purpose

1. Moderators Dr .M.Nagendra Babu ( Professor) Dr.K.RamKumar Reddy (Asso.Professor) Dr.T.Koner Rao (Asst.Professor) Dr.Jaisingh Rathod (Asst.Professor) Presented by Dr. B.Kiran Kumar , P.G in Orthopaedics . BIODEGRADABLE MATERIALS & IMPLANTS

2. INTRODUCTION Orthopaedic surgery has evolved in the last 2 centuries from surgeons using amputation saws on mangled limbs, to modified forms of external splintages and tractions , to sophisticated internal fixation implants and devices that have allowed early mobilization and pain free locomotion. Most of the focus in modern orthopaedic implant development is on developing devices that are stronger, more acceptable to the body, cheaper and durable.

3. In the past few decades a lot of research has been done and significant improvement has been seen in the development of bioabsorbable osteosynthetic devices. Biodegradable implants have allowed a paradigm shift away from bionic (mechanical replacement) engineering and toward true biologic solutions to reconstructive problems

4. Further disadvantages to having metal plates, pins, mesh or other metallic implants inside the body include: • Accumulation of metals in tissues • Hypersensitivity to titanium • Growth restriction • Pain • Corrosion • Implant migration • Imaging and radiotherapy interference

5. Definition Biodegradable refers to a biologically assisted degradation process. Within orthopaedics , terms such as bioabsorbable and resorbable refer to the use of biodegradable materials.

6. History Low molecular weight Polyglycolic acid was synthesized by Bischoff and Walden in 1893. The first synthetic absorbable suture was developed from Polyglycolic acid (PGA) by American Cyanamid Co. in 1962. The 90:10 copolymer of glycolide and lactide - polygalactin - has been applied as the competitive suture ' Vicryl ' since 1975. Since then sutures of polyglycolide and polylactide have been used for many years and no carcinogenic, teratogenic , toxic, or allergic side effects have been observed. The only adverse reaction reported has been a mild non specific inflammation.

7. Use of PGA as reinforcing pins, screws, and plates for bone surgery was first suggested by Schmitt and Polistina  in 1969. Since then there has been a lot of development in manufacturing biodegradable implants with properties appropriate for osteosynthesis .

8. Materials All products are chemically based on lactic or glycolic acid Many are combinations of the two Polydioxanone (PDS) 1991 – Too flexible Polyhydroxybutyrate (PHB) Polycaprolactone (PCL) Polyglycolic acid (PGA) 1991 – Undesirable tissue reaction Polylactic acid (PLA) – 1994. Polylevolactic acid (PLLA) Poly-D-Lactic acid (PDLA) Currently, PGA, PDS, polylevolactic acid(PLLA), and racemic poly(D, L)-lactic acid (PDLLA) are the primary alpha polyesters used for bioabsorbable implants

9. What makes a good material? Mechanical properties match the application, remaining sufficiently strong until the surrounding tissue has healed No inflammatory, toxic, or carcinogenic response Metabolized after fulfilling purpose, leaves no trace Consistently reproducible Demonstrates acceptable shelf life Easily sterilized

10. PGA Semi-crystalline structure Stronger acid than PLA More hydrophilic and thus more susceptible to hydrolysis than PLA Complete strength loss by 1 month Fully degrades in 3 months

11. Biocompatibility of PGA Although highly crystalline, becomes absorbed very quickly Broken down into glycine and glycolic acid Glycine enters TCA cycle Glycolic acid can accumulate and lower local pH PGA is degraded by hydrolysis primarily to pyruvic acid and is excreted as carbon dioxide and water.

12. PLA Semi-crystalline structure Two stereo isomers – L and D lactide Presence of methyl groups makes it more hydrophobic than PGA Complete mass loss in 5-6 years PLLA – most commonly used in orthopaedic fixation Hydrophobic, thus resistant to hydrolysis

13. Biocompatibility of PLA Excellent biocompatibility and slow degradation No inflammatory cell infiltrates have been reported Foreign body reaction limited to peri -implant Broken down into lactic acid and enters TCA cycle. PDLLA is similarly hydrolyzed via the TCA cycle to CO2 and water and excreted by respiration.

14. The Reality Most absorbable fixation is a composite of PGA, PLLA, PDLLA Attain the benefits of each material while limiting the disadvantages Specific composition depends on manufacturer as well as application

15. Structure, strength and properties Polyglycolic acid (PGA) is a hard, tough, crystalline polymer with an average molecular weight of 20,000 to 145,000 and a melting point of 224-230°C. Polylactic acid (PLA) on the other hand is a polymer with initial molecular weights of 180,000 to 530,000 and a melting point of about 174°C. In orthopaedic implants poly-L-lactic acid (PLLA) has been used more extensively because it retains its initial strength longer than poly-D-lactic acid (PDLA). PGA belongs to the category of fast degrading polymers, and intraosseously implanted PGA screws have been shown to completely disappear within 6 months. PLLA on the other hand has a very long degradation time and has been shown to persist in tissues for as long as 5 years post implantation.

16. For Orthopaedic usage, the main hindrance to development of bioabsorbable implants is obtaining sufficient initial strength and retaining this strength in the bone. With the use of self reinforcing (SR) technique the material was sintered together at high temperature and pressure, resulting in initial strengths 5 to 10 times higher than those implants manufactured with melt moulding technique. Though initial strengths of SR-PLLA screws are lower than SR-PGA, retention in the former is longer than the latter. Now a- days, bio­absorbable implants show no difference in the stiffness, linear load & failure mode when compared with metallic devices.

17. FACTORS AFFECTING THE BIOMECHANICAL PROPERTIES OF BIOABSORBABLE POLYMERS: Chemical Composition Molecular weight Viscosity Molar ratio of copolymers Sequence of chains Crystallinity Manufacturing Processes Machining Extrusion Melt molding Compression molding Injection molding Fiber reinforcement Sterilization

18. Physical Dimensions Diameter Mechanical designs Environmental Temperature pH Blood flow Rate of removal of degraded polymer Oxidation/air exposure Enzymatic action Time Viscoelasticity Rate of degradation

19. Physical Properties Molecular weight Effects mechanical properties and degradation High M.wt = slower degradation Intrinsic viscosity Measure of resistance to flow High M.wt = high viscosity Crystallinity Crystaline , semi- crystaline , amorphous More crystalline = more strength More amorphous = faster absorption

20. Porosity – low porous – enhances auto catalysis Glass transition temperature - the temperature at which the compound becomes as hard as glass. Temp below- polymer is stiff and hard Temp above -soft and rubbery Polymers used clinically have GTT above body temp. Physical Properties

21. Mechanical Properties Ductility Amount of plastic strain the polymer will withstand without fracturing Elastic modulus Stiffness of the polymer Depends primarily on the crystallinity

22. Degradation: Crystalline polymers have a regular internal structure and because of the orderly arrangement are slow to degrade. Amorphous polymers have a random structure and are completely and more easily degraded. Semi-crystalline polymers have crystalline and amorphous (random structure) regions. Hydrolysis begins at the amorphous area leaving the more slowly degrading crystalline debris  .   Some earlier biodegradable implants have had problems with degradation time and tissue reactions .

23. One commonly used material, Polyglycolide (PGA), is hydrophilic and degrades very quickly, losing virtually all strength within one month and all mass within 6-12 months. Adverse reactions can occur if the rate of degradation exceeds the limit of tissue tolerance  incidence of adverse tissue reactions to implants made of PGA - 2.0 to 46.7%. So PGA in isolation is rarely used these days in the manufacture of bioabsorbable implants

24. Poly L Lactic Acid (PLLA), has a much slower rate of absorption. This homopolymer of L lactide is highly crystalline due to the ordered pattern of the polymer chains and has been documented to take >5 yrs to absorb. The newer generation of implants remain predominantly amorphous after manufacturing due to controlled production processes of copolymers. D Lactide when copolymerized with L Lactide increases the amorphous nature of these implants. This increases the bioabsorbability of these devices. The ideal material is perhaps one that has a "medium" degradation time of around 2 years.

25. Degradation Affected by many factors Implant size Material type Molecular weight Material phase (crystalline Vs amorphous) Presence of additives / impurities Implantation site ( vascularity ) Age and health status

26. Degradation Begins on contact with tissues Phase I Hydrolysis water penetrates the biodegradable device, initially cutting the chemical bonds and converting the long polymer chains into shorter and shorter fragments

27. Degradation Phase II Metabolism The fragments are degraded into natural monomeric acids found in the body, such as lactic acid. “TCA cycle”-These acids enter the Kreb’s (citric acid) cycle and are metabolised into CO2 and water which are then exhaled and excreted in phase three.

28. Biodegradable implants have many advantages over metal implants, specifically for: • Patients No additional surgery required for implant removal No permanent implant in the body Safe and biocompatible material, no risk of metal allergic reactions Reduced trauma No long-term implant palpability No implant temperature sensitivity Advantages:

29. • Clinicians Compatible with Magnetic Resonance Imaging (MRI) for postoperative diagnosis Reduced radiographic scatter/obstruction Minimised risk of obstruction during any follow-up surgery Increased patient satisfaction • Additional benefits Predictable degradation to provide progressive bone loading, preventing stress shielding to aid better bone healing Reduced total cost - no removal operation Provided sterile reducing risk of cross infection No growth disturbances in children Allows micro-movement to aid fracture healing Advantages:

30. Disadvantages: Primarily the inadequate stiffness of the device and weakness compared to metal implant can pose implantation difficulties like screw breakage during insertion and also make early mobilization precarious. The other potential disadvantages are an inflammatory response described with bioabsorbable implants, rapid loss of initial implant strength and higher refracture rates. Bostman et al reported an 11% incidence of foreign body reaction to PGA screws in malleolar fractures.

31. INDICATIONS FOR ABSORBABLE FIXATION DEVICES Metatarsal osteotomies ( hallux valgus ) Metacarpal and metatarsal fusions Malleolar fractures Osteochondritis dissecans Fractures of the radius and olecranon Epiphyseal fractures Ruptures of the ulnar collateral ligament of the thumb Arthroscopic fixation of meniscus lesions Femoral canal occlusion for cement restriction Drug delivery Cell transplantation (e.g., Dermagraft ) Nerve reconstruction (e.g., Neurotube ) Adhesion prevention

32. Indications Pins or rods Osteotomies or fractures of mets that are inherently stable Digital arthrodesis Transarticular fixation Medial column fusion Trauma Intraarticular calcaneal fractures Ankle fractures Physeal injuries in children

33. Indications Screws Displaced malleolar fractures Forefoot osteotomies providing both compression and stability Midfoot and rearfoot fusions

34. Bionx L1 Fully threaded smart screw. L2 Cannulated L3 SmartPin R1 Partial R2 Smartnails

35. Bionx L. Pin insertion kit R. Smart screw insertion set

36. Contraindications Osteoporosis Comminution of fractures Sensitivity to absorbable materials Presence of infection

37. Adverse Reactions Seen most frequently with PGA implants Foreign body reaction Severe synovitis granuloma Formation of: Aseptic inflammation Sterile sinus tract Sterile abscess

38. Adverse Reactions Bone resorption Osteolytic lesions with cystic extensions of implant tracks Osteoarthritis

39. Clinical Presentation of Foreign Body Reaction Usually seen 50-113 days post implantation PGA – avg 11 weeks PLA – avg 4 years Painful, red, fluctuant swelling Suddenly appearing in otherwise normally healed incision Suspected with persistent swelling, erythema and increasing pain Sinus discharge of polymeric debris Extensive skin slough

40. Adverse Reaction Cultures are usually negative Wound drainage may persist 5 weeks – 4 months Acute reaction usually subsides after 4 months and can be replaced by osteoarthritis that may lead to fusions Radiographically see osteolysis along pin tract. Recommended that PGA implants not be used near joint spaces due to FBR with intraarticular dissemination of polymeric debris

41. Allofix Cortical Pins and Screws First used in 1994 Allograft Devitalized, freeze dried cortical pins and screws Average time of graft incorporation is 4 months

42. Allofix Unique benefits Provides osteoconduction giving creeping substitution Better biocompatibility Decreased sterile abscess formation, osteolysis, bone resorption

43. Allofix Disadvantages Concern for transmitted pathogens such as HIV, Hep B & C Possible host rejection Specific insertional instrumentation

44. Current uses: Biodegradable implants are available for stabilization of fractures, osteotomies , bone grafts and fusions particularly in cancellous bones, as well as for reattachment of ligaments, tendons, meniscal tears and other soft tissue structures. Knee:  Arthroscopic surgery is used extensively for ACL reconstruction in the form of interference screws and transfixation screws. Osteochondral fractures can be well fixed by using arthroscopic techniques and biodegradable pins.

45. Shoulder:   Repair and reconstruction of many intra- articular and extra- articular abnormalities in the shoulder, including rotator cuff tears, shoulder instability, and biceps lesions that require labrum repair or biceps tendon tenodesis . Spine:   Bioresorbable implants have significant potential for use in spine surgery. Coe and Vaccaro  published the first clinical series using bioresorbable implants as interbody spacers in lumbar interbody fusion. The clinical and radiographic results of their study allowed them to recommend the use of bioresorbable devices structural interbody support in the TLIF procedure.

46. Paediatric Orthopaedics :   The applications have been widely varied, and the results very successful. Bostman et al showed that self reinforced absorbable rods were suitable for fixation of physeal fractures in children. In 1991, Hope et al had compared the self reinforced absorbable rods with metallic fixation of elbow fractures in children. Partio et al found SR-PLLA screws firm enough for fixation of subtalar extra articular arthrodesis in children. Bioabsorbable fixation technique for pediatric olecranon fractures has been described, with the advantage of avoiding reoperation to remove hardware

47. Hand:   mini-plating systems are available for fixation of fractures, osteotomies and arthrodesis in the wrist and hand.   Miscellaneous:   There are bioabsorbable implants now available for use in humeral condyle , distal radius and ulna, radial head and other metaphyseal areas. Bioabsorbable meshes are available for acetabular reconstructions. Bioabsorbable implants are also variously used in craniomaxillofacial surgery and dental surgery.

48. Future: Bioabsorbable implant research is an evolving science. Resorbable plates can be covalently linked with compounds such as IL-2, and BMP-2 and represents a novel protein delivery technique. BMP-2 covalently linked to resorbable plates has been used to facilitate bone healing. Covalent linking of compounds to plates represents a novel method for delivering concentrated levels of growth factors to a specific site and potentially extending their half-life. An area for future development would have to focus on developing implants that degrade at the "medium term". Since the screw that persists in its track for 5 years or more does not offer the advantage of bioresorbability , newer molecules may have to be studied.

49. Thank you…