Fred R. Rozema

Foreign body reactions to resorbable poly(L-lactide) bone plates and screws used for the fixation of unstable zygomatic fractures.

In a previous article in the Journal of Oral and Maxillofacial Surgery, the initial results of treating 10 patients with solitary, unstable, displaced zygomatic fractures using resorbable poly(L-lactide) (PLLA) plates and screws was reported (Bos et al, 1987). This article describes the long-term results in these patients. Three years postoperatively, four patients returned because they were concerned about an intermittent swelling at the site of implantation. The remaining patients were recalled after the same postoperative period. All patients were examined clinically, and six patients were operated on again for evaluation of the swelling and to investigate the nature of the tissue reaction. The explanted material showed remnants of degraded PLLA surrounded by a dense fibrous capsule. The swelling was classified as a nonspecific foreign body reaction to the degraded PLLA material. Ultrastructural investigation of the degraded material showed an internalization of crystal-like PLLA material in the cytoplasm of various cells.

RESORBABLE POLY(L-LACTIDE) PLATES AND SCREWS FOR THE FIXATION OF ZYGOMATIC FRACTURES

Ten patients with unstable zygomatic fractures were treated with resorbable poly(L-lactide) (PLLA) plates and screws. The results show that this method of fixation gives good stability over a sufficiently long period to enable undisturbed fracture healing.

Resorbable materials of poly(l-lactide). VI. Plates and screws for internal fracture fixation

Poly(L-lactide) (PLLA) with an extremely high molecular weight (Mv up to 1 X 10(6)) was synthesized at a low catalyst concentration (0.015 wt%) and temperatures between 100-110 degrees C. Besides good mechanical properties the as-polymerized PLLA exhibited a microporous structure. Plates and screws of this material were used for the treatment of mandibular fractures, both in dogs and in sheep. Bone healing was uneventful and proceeded without callus formation or signs of inflammation. Fracture healing was accompanied by a progressive degradation of the microporous implants of PLLA.

Resorbable materials of poly(l-lactide): VII. In vivo and in vitro degradation

In vivo and in vitro degradation of high molecular weight poly(L-lactide) used for internal bone fixation has been investigated. Within 3 months as-polymerized, microporous PLLA (Mv = 6.8-9.5 X 10(5] exhibited a massive strength-loss (sigma b = 68-75 MPa to sigma b = 4 MPa) and decrease of Mv (90-95%). At week 39, the first signs of resorption were evident (mass-loss 5 wt%). Except for dynamically loaded bone plates no differences between in vivo and in vitro degradation of PLLA were observed. The increase of crystallinity of PLLA upon degradation (up to 83%) is likely to be attributed to recrystallization of tie-chain segments. A more ductile PLLA exhibiting a lower rate of degradation was prepared by extraction of low molecular weight compounds with ethyl acetate.

In vivo degradation and biocompatibility study of in vitro pre-degraded as-polymerized polylactide particles

The degradation of high molecular weight as-polymerized poly(L-lactide) (PLLA) is very slow; it takes more than 5.6 yr for total resorption. Moreover, the degradation products of as-polymerized PLLA bone plates, consisting of numerous stable particles of high crystallinity, are related with a subcutaneous swelling in patients 3 yr postoperatively. In order to avoid these complications, polymers were developed that are anticipated to have comparable mechanical properties but a higher degradation rate and do not degrade into highly stable particles that can induce a subcutaneous swelling. On chemical grounds it can be expected that copolymerization of PLLA with 4% D-lactide (PLA96) or by modifying PLLA through cross-linking (CL-PLLA) will lead to less stable particles and a higher degradation rate. To evaluate the long-term suitability of these as-polymerized polymers, the biocompatibility of the degradation products should be studied. Considering the very slow degradation rate of as-polymerized PLLA, in vitro pre-degradation at elevated temperatures was used to shorten the in vivo follow-up periods. In this study, the biocompatibility and degradation of as-polymerized PLLA, PLA96 and CL-PLLA were investigated by implanting pre-degraded particulate materials subcutaneously in rats. Animals were killed after a postoperative period varying from 3 to 80 wk. Light and electron microscopical analysis and quantitative measurements were performed. The histological response of all three pre-degraded materials showed a good similarity with in vivo implanted material. Pre-degraded PLLA induced a mild foreign body reaction and showed a slow degradation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Bio-absorbable plates and screws for internal fixation of mandibular fractures: A study in six dogs

Bio-absorbable plates and screws were used for internal fixation of artificially created mandibular fractures in 6 dogs. The plates and screws were fabricated from a block of poly(L-lactide) (PLLA), with a high molecular weight. The material is microporous and has excellent mechanical properties. Plates and screws were inserted in accordance with Champys principles on internal fixation. Clinical and radiographical follow-up and examination of the fracture site under general anesthesia showed that all fractures healed without callus and without complications. The plates or screws did not fail, despite the tensile strength of the PLLA used is less than stainless steel or any other metal. An explanation for their successful application may be the high impact resilience of this material. The proprioceptive mechanisms, however, that keep the dogs from maximal loading of their broken mandibles, may also play a role. Plates and screws of this bio-absorbable PLLA appear to be an attractive alternative for internal fixation of mandibular fractures and certainly for less loaded fractures of the human skeleton. The necessity to remove metallic osteosynthesis can be avoided.

Poly(L-lactide) implants in repair of defects of the orbital floor: An animal study

Because of the life-long presence of alloplastic, nonresorbable orbital floor implants and the complications of their use mentioned in literature, the use of a resorbable material appears to be preferable in the repair of orbital floor defects. A high-molecular-weight, as-polymerized poly(L-lactide) (PLLA) was used for repair of orbital floor defects of the blowout type in goats. An artificial defect was created in the bony floor of both orbits. Reconstruction of the orbital floor was then carried out using a concave PLLA implant of 0.4-mm thickness. At 3, 6, 12, 19, 26, 52, and 78 weeks postoperatively, one goat was killed. Microscopic examination showed full encapsulation of the implant by connective tissue after 3 weeks. After 6 weeks, resorption and remodeling of the bone at the points of support of the implant could be detected. A differentiation between the sinus and orbital sides of the connective tissue capsule was observed. The orbital side showed a significantly more dense capsule than the antral side, which had a loose appearance. At 19 weeks, a bony plate was progressively being formed, and at 78 weeks, new bone had fully covered the plate on the antral and orbital side. No inflammation or rejection of the PLLA implant was seen.

Poly(L-lactide) implants for repair of human orbital floor defects: Clinical and magnetic resonance imaging evaluation of long-term results

PURPOSE The purpose of this study was to evaluate the long-term outcome of repair of orbital floor defects in patients with resorbable as-polymerized poly(L-lactide) (PLLA) implants and to determine whether these patients showed symptoms that could be indicative of the presence of a late tissue response. PATIENTS AND METHODS Six patients (four women, two men; mean age, 39 years; range, 18 to 67 years) treated with PLLA implants for orbital floor fractures were recalled for follow-up examination after a period ranging from 3 1/2 to 6 1/2 years. The examination consisted of an interview and a physical examination, including an ophthalmologic and orthoptic consultation. For evaluation of the orbital tissues, coronal spin echo T1- and T2-weighted magnetic resonance images (MRIs) were made through both orbits. RESULTS None of the patients reported any problems in the years preceding the follow-up examination that might have indicated complications. Clinical examination of the operative sites revealed no abnormalities. At ophthalmologic and orthoptic consultation, normal eye function, without diplopia or restriction of motility, was found in all patients. The MRIs showed no indication of an abnormal or increased soft tissue reaction in the orbital region. CONCLUSIONS Based on the results of this study, it can be concluded that PLLA orbital floor implants have the potential for successful use in repair of human orbital floor defects.

HIGH-IMPACT POLY(L/D-LACTIDE) FOR FRACTURE FIXATION - IN-VITRO DEGRADATION AND ANIMAL PILOT-STUDY

The impact strength of amorphous lactide copolymers can be significantly improved by blending with biodegradable rubbers. Rubber toughening of amorphous poly(85L/15D -lactide) with the copolymer poly (50/50-trimethylenecarbonate-co-epsilon-caprolactone) results in a high-impact polymer (PDLLA/P(TMC-CL)). In vitro, the PDLLA/P(TMC-CL) blend retained its tensile and impact strength for a long period of time. Up to 45 weeks, the amount of water absorbed by the blend remained very low and no significant mass loss was observed. To test the suitability for fracture fixation, in a dog study mandibular fractures were fixated with PDLLA/P(TMC-CL) bone plates and screws. Bone healing was uneventful without premature failure of the implants. Although long-term degradation studies have to be carried out, PDLLA/P(TMC-CL) seems to be promising for application in fracture fixation.

Cytotoxicity of poly(96L/4D-lactide): the influence of degradation and sterilization.

The cytotoxicity of poly(96L/4D-lactide) (PLA96), and of its accumulated degradation products, was investigated following different sterilization methods and pre-determined heat-accelerated degradation intervals. PLA96 samples sterilized by either steam, ethylene oxide, or gamma irradiation were left untreated (S0 samples), or were degraded for 30 h or 60 h (S30 and S60 samples) at 90 degrees C in water. Extracts of the samples and of the remaining degradation fluids (F30 and F60) were prepared. The toxicity of both unfiltered and filtered extracts was analyzed in a cell growth inhibition (CGI) assay and a lactate dehydrogenase (LDH) leakage assay. Physical analysis of the extracted samples and of the degradation fluids also was performed. The S0 extracts demonstrated no significant CGI. The CGI of the S30 extracts ranged from 37 to 78%, whereas the CGI of the S60 extracts ranged from 6 to 33%. The CGI of the F30 extracts ranged from 19 to 38% and the CGI of the F60 extracts was 98 to 123%. The LDH leakage assay only showed a high response to the unfiltered F60 extracts. Neither sterilization nor filtration appeared to influence the cytotoxicity of the extracts. Particle accumulation, however, might affect cell membrane permeability resulting in LDH leakage. The results of this study suggest that the cytotoxicity of PLA96 is related to the pH and possibly the osmolarity of the tested extracts. The pH and osmolarity, in turn, may depend on variations in the amounts of solubilized lactic acid and oligomers. These variations appear to result from degradation stage-dependent differences in crystallinity, molecular weight and molecular weight distribution of the PLA96 samples.