Copolymeric biodegradable osteosynthesis systems are safe to use but degradation takes longer than previously presumed

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Osteosynthesis systems consist of plates and screws, and are used to fixate bone segments after, e.g., fractures of the facial bones. In oral and maxillofacial surgery (OMF-surgery), titanium osteosynthesis systems are considered the gold standard. However, in 1 out of every 5 patients, titanium systems are removed in second operation because of clinical symptoms. Biodegradable osteosynthesis systems are composed of degradable (co)polymers, and can reduce the need for removal of plates and screws in a second operation.

The complete degradation and resorption of these biomaterials was presumed to be within 24 months. In a recent study by Gareb et al. (W.J. Kolff Institute), a group of researchers from the UMCG, Radboudumc and University of Twente have collaborated to assess the in vivo biocompatibility and degradation profiles of four copolymeric biodegradable osteosynthesis systems used in OMF-surgery.  The study showed that all the biodegradable systems were safe to use and were well-tolerated. However, nanoscale polymeric fragments of all four copolymeric systems were still observed  at the 4-year follow-up. Whether these nanoparticles may be harmful on the long run (i.e., >4 years) is not clear.

Figure legend: 6 different biodegradable plates (from left to right: plates 1-6) and 2 different titanium plates (plates 7-8).

The disadvantages of titanium osteosynthesis systems include sensitivity due to environmental temperature changes, tactile sensation of plates and screws, possible growth restrictions in children, hampering of imaging and radiotherapy, and leeching of titanium particles in surrounding lymph nodes. Consequently, titanium systems often have to be removed in a second operation. Biodegradable osteosynthesis systems are commonly composed of degradable (co)polymers (e.g.,  polylactide) and may reduce removal rates of these osteosynthesis systems in a second operation while also avoiding the aforementioned disadvantages of titanium osteosyntheses. Biodegradable systems have, however, their own limitations including decreased mechanical properties. In addition, foreign body reactions remain a major concern and evidence of complete resorption is lacking. Therefore, the study aimed to assess and compare the histological responses of four commonly used copolymeric biodegradable osteosynthesis systems in a goat model up to a four-year follow-up. These insights are essential for biocompatibility evaluations as well as to gain knowledge of the development of foreign body reactions to such biodegradable polymers.

The current study

The BioSorb FX [poly(70L-lactic acid-co-30D,L-lactic acid)], Inion CPS [poly([70–78.5]L-lactic acid-co-[16–24]DL-lactic acid-co-4trimethylene carbonate)], SonicWeld Rx [poly(DL-lactic acid], LactoSorb [poly(82L-lactic acid-co-18glycolic acid)] osteosynthesis systems and a negative control were randomly implanted in each extremity of 12 goats. Samples were assessed at 6-, 12-, 18-, 24-, 36- and 48-month follow-up. Surface topography was performed using scanning electron microscopy (SEM). Differential scanning calorimetry and gel permeation chromatography were performed on initial and explanted samples to assess the physico-chemical properties. Histological sections were systematically assessed by two blinded researchers using (polarised) light microscopy, SEM and energy-dispersive X-ray analysis. 

The results showed that the SonicWeld Rx system was amorphous while the others were semi-crystalline. Foreign-body reactions were not observed during follow-up. The implant sites of the SonicWeld Rx and LactoSorb systems reached newly formed bone percentages similar to negative controls after 18 months while the BioSorb FX and Inion CPS systems reached these levels after 36 months. The SonicWeld Rx system showed the most predictable degradation profile. All the biodegradable systems were safe to use and well-tolerated (i.e., complete implant replacement by bone, no clinical or histological foreign body reactions, no [sterile] abscess formation, no re-interventions needed), but nanoscale residual polymeric fragments were observed at every system's assessment. This study emphasises that biodegradable copolymeric biomaterials are safe to use, but that the degradation takes longer than previously presumed.
Several key factors could be assigned for a predictable degradation profile. Preferably, biodegradable osteosynthesis systems are composed of (1) completely amorphous (co)polymers (e.g., poly[DL-lactic acid]) with (2) low intrinsic viscosity. In addition, the systems should have (3) well-contoured shapes without acute angles (e.g., by welding pins instead of using screws), (4) a smooth and homogenous surface, and (5) low implant volume but with sufficient mechanical properties for the purpose of the implant.


Since it is unclear whether these nanoparticles may be harmful, the next essential step in biocompatibility assessment of biodegradable copolymeric osteosynthesis systems should be to assess whether the amount of observed nanoparticles is able to induce a foreign body reaction on the long-run. Therefore, nanoparticles could be implanted in large animal models to assess the long-term outcome. A more ethical alternative would be to seek for new in vitro techniques for analysing biological response to biomaterials such as foreign body reactions on a chip and complex cell-culture systems mimicking in vivo tissue environments without the need for sacrificing animals for scientific research. These new techniques are currently being developed and the results are eagerly awaited.

The results of this study are published open access in Bioactive Materials.
Read the study: "Biocompatibility and degradation comparisons of four biodegradable copolymeric osteosynthesis systems used in maxillofacial surgery: A goat model with four years follow-up"