Can Hardware Removal be Avoided Using Bioresorbable Mg-Zn-Ca Screws After Medial Malleolar Fracture Fixation? Mid-Term Results of a First-In-Human Study

Magnesium (Mg)-based implants are highly attractive for the orthopedic field and may replace titanium (Ti) as support for fracture healing. To determine the implant-bone-interaction in different bony regions, we implanted Mg-based alloy ZX00 (Mg < 0.5 Zn < 0.5 Ca, in wt%) and Ti-screws into the distal epiphysis and distal metaphysis of sheep tibiae. The implant degradation and osseointegration were assessed in vivo and ex vivo after 4, 6 and 12 weeks, using a combination of clinical computed tomography (cCT), medium-resolution micro CT (µCT) and high-resolution synchrotron radiation µCT (SRµCT). Implant volume loss, gas formation, and bone growth were evaluated for both implantation sites and each bone region independently. Additionally, histological analysis of bone growth was performed on embedded hard-tissue samples. We demonstrate that in all cases, the degradation rate of ZX00-implants ranges between 0.23-0.75 mm/year. The highest degradation rates were found in the epiphysis. Bone-to-implant-contact varied between the time points and bone types for both materials. Mostly, bone-volume-to-total-volume was higher around Ti-implants. However, we found an increased cortical thickness around the ZX00-screws when compared to the Ti-screws. Our results showed the suitability of ZX00-screws for implantation into the distal meta- and epiphysis.

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“…[ 8 ] and Herber et al . [ 9 ]. They showed highly satisfactory results in two clinical studies using ZX00-screws for fracture treatment.…”

Section: Discussionmentioning

confidence: 99%

“…[ 8 ] and Herber et al . [ 9 ] showed a good clinical outcome after operative treatment of medial malleolus fractures with ZX00-screws in humans. However, implant degradation is strongly influenced by the direct environment, such as tissue types of the peri-implant area.…”

Section: Introductionmentioning

confidence: 99%

Degradation behavior and osseointegration of Mg–Zn–Ca screws in different bone regions of growing sheep: a pilot study

Marek

Ćwieka

Donohue

et al. 2022

Regenerative Biomaterials

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“…Some examples of pre-clinical in vivo studies using ZX systems are given in refs. [ 58 , 59 , 60 ], suggesting a bright future for biodegradable Mg-based orthopedic implants.…”

Section: Motivationmentioning

confidence: 99%

Attaining High Functional Performance in Biodegradable Mg-Alloys: An Overview of Challenges and Prospects for the Mg-Zn-Ca System

et al. 2023

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This article presents a concise overview of modern achievements and existing knowledge gaps in the area of biodegradable magnesium alloys. Hundreds of Mg-based alloys have been proposed as candidates for temporary implants, and this number tends to increase day by day. Therefore, while reviewing common aspects of research in this field, we confine ourselves primarily to the popular Mg-Zn-Ca system, taken as a representative example. Over the last decades, research activities in this area have grown enormously and have produced many exciting results. Aiming at highlighting the areas where research efforts are still scarce, we review the state-of-the-art processing techniques and summarize the functional properties attained via a wide variety of processing routes devised towards achieving a desired properties profile, including the mechanical response in terms of strength, ductility, and fatigue resistance paired with biocompatibility and bio-corrosion resistance or controlled degradability. We pay keen attention to a summary of corrosion properties and mechano-chemical interactions between an aggressive environment and loaded Mg-based structures, resulting in stress corrosion cracking and premature corrosion fatigue failures. The polemic issues and challenges practitioners face in their laboratory research are identified and discussed.

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“…The biocompatibility and resorption of ZX00 has been investigated in mouse and sheep models [7,20], including proof-of-concept for successful fixation of osteotomies [9]. The first in-human Mg-alloy (ZX00) screw implantations were performed in 2018 and 2019 [8,10], when feasibility in the clinical environment was demonstrated with a medial malleolar fracture model. Successful healing of the medial malleolar fracture was achieved with Mg-alloy (ZX00) screws, avoiding screw removal.…”

Section: Introductionmentioning

confidence: 99%

Mg-Zn-Ca Alloy (ZX00) Screws Are Resorbed at a Mean of 2.5 Years After Medial Malleolar Fracture Fixation: Follow-up of a First-in-humans Application and Insights From a Sheep Model

Labmayr,

Suljevic,

Sommer

et al. 2023

Clin Orthop Relat Res

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Background In the ongoing development of bioresorbable implants, there has been a particular focus on magnesium (Mg)-based alloys. Several Mg alloys have shown promising properties, including a lean, bioresorbable magnesium-zinc-calcium (Mg-Zn-Ca) alloy designated as ZX00. To our knowledge, this is the first clinically tested Mg-based alloy free from rare-earth elements or other elements. Its use in medial malleolar fractures has allowed for bone healing without requiring surgical removal. It is thus of interest to assess the resorption behavior of this novel bioresorbable implant. Questions/purposes (1) What is the behavior of implanted Mg-alloy (ZX00) screws in terms of resorption (implant volume, implant surface, and gas volume) and bone response (histologic evaluation) in a sheep model after 13 months and 25 months? (2) What are the radiographic changes and clinical outcomes, including patient-reported outcome measures, at a mean of 2.5 years after Mg-alloy (ZX00) screw fixation in patients with medial malleolar fractures? Methods A sheep model was used to assess 18 Mg-alloy (ZX00) different-length screws (29 mm, 24 mm, and 16 mm) implanted in the tibiae and compared with six titanium-alloy screws. Micro-CT was performed at 13 and 25 months to quantify the implant volume, implant surface, and gas volume at the implant sites, as well as histology at both timepoints. Between July 2018 and October 2019, we treated 20 patients with ZX00 screws for medial malleolar fractures in a first-in-humans study. We considered isolated, bimalleolar, or trimalleolar fractures potentially eligible. Thus, 20 patients were eligible for follow-up. However, 5% (one patient) of patients were excluded from the analysis because of an unplanned surgery for a pre-existing osteochondral lesion of the talus performed 17 months after ZX00 implantation. Additionally, another 5% (one patient) of patients were lost before reaching the minimum study follow-up period. Our required minimum follow-up period was 18 months to ensure sufficient time to observe the outcomes of interest. At this timepoint, 10% (two patients) of patients were either missing or lost to follow-up. The follow-up time was a mean of 2.5 ± 0.6 years and a median of 2.4 years (range 18 to 43 months). Results In this sheep model, after 13 months, the 29-mm screws (initial volume: 198 ± 1 mm3) degraded by 41% (116 ± 6 mm3, mean difference 82 [95% CI 71 to 92]; p < 0.001), and after 25 months by 65% (69 ± 7 mm3, mean difference 130 [95% CI 117 to 142]; p < 0.001). After 13 months, the 24-mm screws (initial volume: 174 ± 0.2 mm3) degraded by 51% (86 ± 21 mm3, mean difference 88 [95% CI 52 to 123]; p = 0.004), and after 25 months by 72% (49 ± 25 mm3, mean difference 125 [95% CI 83 to 167]; p = 0.003). After 13 months, the 16-mm screws (initial volume: 112 ± 5 mm3) degraded by 57% (49 ± 8 mm3, mean difference 63 [95% CI 50 to 76]; p < 0.001), and after 25 months by 61% (45 ± 10 mm3, mean difference 67 [95% CI 52 to 82]; p < 0.001). Histologic evaluation qualitatively showed ongoing resorption with new bone formation closely connected to the resorbing screw without an inflammatory reaction. In patients treated with Mg-alloy screws after a mean of 2.5 years, the implants were radiographically not visible in 17 of 18 patients and the bone had homogenous texture in 15 of 18 patients. No clinical or patient-reported complications were observed. Conclusion In this sheep model, Mg-alloy (ZX00) screws showed a resorption to one-third of the original volume after 25 months, without eliciting adverse immunologic reactions, supporting biocompatibility during this period. Mg-alloy (ZX00) implants were not detectable on radiographs after a mean of 2.5 years, suggesting full resorption, but further studies are needed to assess environmental changes regarding bone quality at the implantation site after implant resorption. Clinical Relevance The study demonstrated successful healing of medial malleolar fractures using bioresorbable Mg-alloy screws without clinical complications or revision surgery, resulting in pain-free ankle function after 2.5 years. Future prospective studies with larger samples and extended follow-up periods are necessary to comprehensively assess the long-term effectiveness and safety of ZX00 screws, including an exploration of limitations when there is altered bone integrity, such as in those with osteoporosis. Additional use of advanced imaging techniques, such as high-resolution CT, can enhance evaluation accuracy.

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Can Hardware Removal be Avoided Using Bioresorbable Mg-Zn-Ca Screws After Medial Malleolar Fracture Fixation? Mid-Term Results of a First-In-Human Study

Cited by 18 publications

References 35 publications

Degradation behavior and osseointegration of Mg–Zn–Ca screws in different bone regions of growing sheep: a pilot study

Degradation behavior and osseointegration of Mg–Zn–Ca screws in different bone regions of growing sheep: a pilot study

Attaining High Functional Performance in Biodegradable Mg-Alloys: An Overview of Challenges and Prospects for the Mg-Zn-Ca System

Mg-Zn-Ca Alloy (ZX00) Screws Are Resorbed at a Mean of 2.5 Years After Medial Malleolar Fracture Fixation: Follow-up of a First-in-humans Application and Insights From a Sheep Model

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