Resorbable magnesium metal membrane for sinus lift procedures: a case series.

BACKGROUND: The purpose of this case series was to demonstrate the use of a magnesium membrane for repairing the perforated membrane in both direct and indirect approaches, as well as its application in instances where there has been a tear of the Schneiderian membrane. CASE PRESENTATION: The case series included four individual cases, each demonstrating the application of a magnesium membrane followed by bone augmentation using a mixture of xenograft and allograft material in the sinus cavity. In the first three cases, rupture of Schneiderian membrane occurred as a result of tooth extraction, positioning of the dental implant, or as a complication during the procedure. In the fourth case, Schneiderian membrane was perforated as a result of the need to aspirate a polyp in the maxillary sinus. In case one, 10 mm of newly formed bone is visible four months after graft placement. Other cases showed between 15 and 20 mm of newly formed alveolar bone. No residual magnesium membrane was seen on clinical inspection. The vertical and horizontal augmentations proved stable and the dental implants were placed in the previously grafted sites. CONCLUSION: Within the limitations of this case series, postoperative clinical examination, and panoramic and CBCT images demonstrated that resorbable magnesium membrane is a viable material for sinus lift and Schneiderian membrane repair. The case series showed successful healing and formation of new alveolar bone with separation of the oral cavity and maxillary sinus in four patients.

Degradation, Bone Regeneration and Tissue Response of an Innovative Volume Stable Magnesium-Supported GBR/GTR Barrier Membrane.

INTRODUCTION: Bioresorbable collagenous barrier membranes are used to prevent premature soft tissue ingrowth and to allow bone regeneration. For volume stable indications, only non-absorbable synthetic materials are available. This study investigates a new bioresorbable hydrofluoric acid (HF)-treated magnesium (Mg) mesh in a native collagen membrane for volume stable situations. MATERIALS AND METHODS: HF-treated and untreated Mg were compared in direct and indirect cytocompatibility assays. In vivo, 18 New Zealand White Rabbits received each four 8 mm calvarial defects and were divided into four groups: (a) HF-treated Mg mesh/collagen membrane, (b) untreated Mg mesh/collagen membrane (c) collagen membrane and (d) sham operation. After 6, 12 and 18 weeks, Mg degradation and bone regeneration was measured using radiological and histological methods. RESULTS: In vitro, HF-treated Mg showed higher cytocompatibility. Histopathologically, HF-Mg prevented gas cavities and was degraded by mononuclear cells via phagocytosis up to 12 weeks. Untreated Mg showed partially significant more gas cavities and a fibrous tissue reaction. Bone regeneration was not significantly different between all groups. DISCUSSION AND CONCLUSIONS: HF-Mg meshes embedded in native collagen membranes represent a volume stable and biocompatible alternative to the non-absorbable synthetic materials. HF-Mg shows less corrosion and is degraded by phagocytosis. However, the application of membranes did not result in higher bone regeneration.

Electrochemical removal of metallic implants from Technovit 9100 New embedded hard and soft tissues prior to histological sectioning.

Solid metallic implants in soft or hard tissues are serious challenges for histological processing. However, metallic implants are more frequently used in e.g. cardiovascular or orthopaedic therapies. Before clinical use, these devices need to be tested thoroughly in a biological environment and histological analysis of their biocompatibility is a major requirement. To allow the histological analysis of metallic implants in tissues especially in calcified hard tissues, we describe a method for embedding these tissues in the resin Technovit 9100 New and removing the metallic implants by electrochemical dissolution. With the combination of these two processes, we are able to achieve 5 µm thick sections from soft or hard tissues with a superior preservation of tissue architecture and especially the implant-tissue interface. These sections can be stained by classical stainings, immunohistochemical and enzymehistochemical as well as DNA-based staining methods.

Open-porous magnesium-based scaffolds withstand in vitro corrosion under cyclic loading: A mechanistic study.

The successful application of magnesium (Mg) alloys as biodegradable bone substitutes for critical-sized defects may be comprised by their high degradation rate resulting in a loss of mechanical integrity. This study investigates the degradation pattern of an open-porous fluoride-coated Mg-based scaffold immersed in circulating Hanks' Balanced Salt Solution (HBSS) with and without in situ cyclic compression (30 N/1 Hz). The changes in morphological and mechanical properties have been studied by combining in situ high-resolution X-ray computed tomography mechanics and digital volume correlation. Although in situ cyclic compression induced acceleration of the corrosion rate, probably due to local disruption of the coating layer where fatigue microcracks were formed, no critical failures in the overall scaffold were observed, indicating that the mechanical integrity of the Mg scaffolds was preserved. Structural changes, due to the accumulation of corrosion debris between the scaffold fibres, resulted in a significant increase (p < 0.05) in the material volume fraction from 0.52 ± 0.07 to 0.47 ± 0.03 after 14 days of corrosion. However, despite an increase in fibre material loss, the accumulated corrosion products appear to have led to an increase in Young's modulus after 14 days as well as lower third principal strain (εp3) accumulation (-91000 ± 6361 µÎµ and -60093 ± 2414 µÎµ after 2 and 14 days, respectively). Therefore, this innovative Mg scaffold design and composition provide a bone replacement, capable of sustaining mechanical loads in situ during the postoperative phase allowing new bone formation to be initially supported as the scaffold resorbs.

Application of Biodegradable Magnesium Membrane Shield Technique for Immediate Dentoalveolar Bone Regeneration.

For the first time, the clinical application of the first CE registered magnesium membrane is reported. Due to the material characteristics of magnesium metal, new treatment methodologies become possible. This has led to the development of a new technique: the magnesium membrane shield technique, used to rebuild the buccal or palatal walls of compromised extraction sockets. Four clinical cases are reported, demonstrating the handling options of this new technique for providing a successful regenerative outcome. Using the technique, immediate implant placement is possible with a provisional implant in the aesthetic zone. It can also be used for rebuilding both the buccal and palatal walls simultaneously. For instances where additional mechanical support is required, the membrane can be bent into a double layer, which additionally provides a rounder edge for interfacing with the soft tissue. In all reported clinical cases, there was a good bone tissue regeneration and soft tissue healing. In some instances, the new bone had formed a thick cortical bone visible in cone beam computed tomography (CBCT) radiographs of the regenerated sites, which is known to be remodeled in the post treatment period. Overall, the magnesium membrane shield technique is presented as an alternative treatment option for compromised extraction sockets.

Immunomodulatory biomaterials against bacterial infections: Progress, challenges, and future perspectives.

Bacterial infectious diseases are one of the leading causes of death worldwide. Even with the use of multiple antibiotic treatment strategies, 4.95 million people died from drug-resistant bacterial infections in 2019. By 2050, the number of deaths will reach 10 million annually. The increasing mortality may be partly due to bacterial heterogeneity in the infection microenvironment, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants. In addition, the complexity of the immune microenvironment at different stages of infection makes biomaterials with direct antimicrobial activity unsatisfactory for the long-term treatment of chronic bacterial infections. The increasing mortality may be partly attributed to the biomaterials failing to modulate the active antimicrobial action of immune cells. Therefore, there is an urgent need for effective alternatives to treat bacterial infections. Accordingly, the development of immunomodulatory antimicrobial biomaterials has recently received considerable interest; however, a comprehensive review of their research progress is lacking. In this review, we focus mainly on the research progress and future perspectives of immunomodulatory antimicrobial biomaterials used at different stages of infection. First, we describe the characteristics of the immune microenvironment in the acute and chronic phases of bacterial infections. Then, we highlight the immunomodulatory strategies for antimicrobial biomaterials at different stages of infection and their corresponding advantages and disadvantages. Moreover, we discuss biomaterial-mediated bacterial vaccines' potential applications and challenges for activating innate and adaptive immune memory. This review will serve as a reference for future studies to develop next-generation immunomodulatory biomaterials and accelerate their translation into clinical practice.

In vitro corrosion of ZEK100 plates in Hank's Balanced Salt Solution.

BACKGROUND: In recent years magnesium alloys have been intensively investigated as potential resorbable materials with appropriate mechanical and corrosion properties. Particularly in orthopedic research magnesium is interesting because of its mechanical properties close to those of natural bone, the prevention of both stress shielding and removal of the implant after surgery. METHODS: ZEK100 plates were examined in this in vitro study with Hank's Balanced Salt Solution under physiological conditions with a constant laminar flow rate. After 14, 28 and 42 days of immersion the ZEK100 plates were mechanically tested via four point bending test. The surfaces of the immersed specimens were characterized by SEM, EDX and XRD. RESULTS: The four point bending test displayed an increased bending strength after 6 weeks immersion compared to the 2 week group and 4 week group. The characterization of the surface revealed the presence of high amounts of O, P and Ca on the surface and small Mg content. This indicates the precipitation of calcium phosphates with low solubility on the surface of the ZEK100 plates. CONCLUSIONS: The results of the present in vitro study indicate that ZEK100 is a potential candidate for degradable orthopedic implants. Further investigations are needed to examine the degradation behavior.

Biomechanical characterisation of a degradable magnesium-based (MgCa0.8) screw.

Magnesium alloys have been in the focus of research in recent years as degradable biomaterial. The purpose of this study was the biomechanical characterisation of MgCa0.8-screws. The maximum pull out force of screws was determined in a synthetic bone without corrosion and after fixed intervals of corrosion: 24, 48, 72 and 96 h. This in vitro study has been carried out with Hank's solution with a flow rate corresponding to the blood flow in natural bone. A maximum pull out force (F(max)) of 201.5 ± 9.3 N was measured without corrosion. The biomechanical parameter decreased by 30% after 96 h in corrosive medium compared to the non-corrosion group. A maximum load capacity of 28 ± 7.6 N/h was determined. Our biomechanical data suggests that this biodegradable screw provides a promising bone-screw-fixation and has great potential for medical application.

Exploring the degradation behavior of MgXAg alloys by in vitro electrochemical methods.

Magnesium as biodegradable biomaterial could serve as bone augmentation material in implant dentistry. The knowledge about the predictability of the biodegradation process is essential as this process needs to go hand in hand with the formation of new bone to gradually replace the augmentation material. Therefore, this work aimed to assess if the electrochemistry (EC) measurements of the corrosion process correlate with the surface features at various time points during the surface degradation, in order to describe the degradation process of Mg and Mg alloys more reliably, under the assumption that differences in EC behavior can be detected and related to specific patterns on the surface. In this test setup, a special optical chamber was used for electrochemical measurements on Mg and Mg-alloys (Mg2Ag, Mg4Ag, and Mg6Ag). Specimens were investigated using different circulating cell culture solutions as electrolytes, these were minimum essential medium (MEM), Hank's Balanced Salt Solution (HBSS), and MEM+ (MEM with added sodium hydrogen carbonate) at 37 °C. Open circuit potential measurements (OCP) over 30 min followed by cyclic polarization were performed. The electrochemistry data, including OCP, exchange current density and corrosion potential, were compared with visible changes at the surface during these treatments over time. The results show that the addition of silver (Ag) leads to a "standardization" of the degradation regardless of the selected test medium. It is currently difficult to correlate the visible microscopic changes with the data taken from the measurements. Therefore, further investigations are necessary.

Analysis of a Pure Magnesium Membrane Degradation Process and Its Functionality When Used in a Guided Bone Regeneration Model in Beagle Dogs.

For the surgical technique of guided bone regeneration (GBR), the choice of available barrier membranes has until recently not included an option that is mechanically strong, durable, synthetic and resorbable. The most commonly used resorbable membranes are made from collagen, which are restricted in their mechanical strength. The purpose of this study is to evaluate the degradation and regeneration potential of a magnesium membrane compared to a collagen membrane. In eighteen beagle dogs, experimental bone defects were filled with bovine xenograft and covered with either a magnesium membrane or collagen membrane. The health status of the animals was regularly monitored and recorded. Following sacrifice, the hemimandibles were prepared for micro-CT (µ-CT) analysis. Complications during healing were observed in both groups, but ultimately, the regenerative outcome was similar between groups. The µ-CT parameters showed comparable results in both groups in terms of new bone formation at all four time points. In addition, the µ-CT analysis showed that the greatest degradation of the magnesium membranes occurred between 1 and 8 weeks and continued until week 16. The proportion of new bone within the defect site was similar for both treatment groups, indicating the potential for the magnesium membrane to be used as a viable alternative to collagen membranes. Overall, the new magnesium membrane is a functional and safe membrane for the treatment of defects according to the principles of GBR.

Sustained local ionic homeostatic imbalance caused by calcification modulates inflammation to trigger heterotopic ossification.

Heterotopic ossification (HO) is a condition triggered by an injury leading to the formation of mature lamellar bone in extraskeletal soft tissues. Despite being a frequent complication of orthopedic and trauma surgery, brain and spinal injury, the etiology of HO is poorly understood. The aim of this study is to evaluate the hypothesis that a sustained local ionic homeostatic imbalance (SLIHI) created by mineral formation during tissue calcification modulates inflammation to trigger HO. This evaluation also considers the role SLIHI could play for the design of cell-free, drug-free osteoinductive bone graft substitutes. The evaluation contains five main sections. The first section defines relevant concepts in the context of HO and provides a summary of proposed causes of HO. The second section starts with a detailed analysis of the occurrence and involvement of calcification in HO. It is followed by an explanation of the causes of calcification and its consequences. This allows to speculate on the potential chemical modulators of inflammation and triggers of HO. The end of this second section is devoted to in vitro mineralization tests used to predict the ectopic potential of materials. The third section reviews the biological cascade of events occurring during pathological and material-induced HO, and attempts to propose a quantitative timeline of HO formation. The fourth section looks at potential ways to control HO formation, either acting on SLIHI or on inflammation. Chemical, physical, and drug-based approaches are considered. Finally, the evaluation finishes with a critical assessment of the definition of osteoinduction. STATEMENT OF SIGNIFICANCE: The ability to regenerate bone in a spatially controlled and reproducible manner is an essential prerequisite for the treatment of large bone defects. As such, understanding the mechanism leading to heterotopic ossification (HO), a condition triggered by an injury leading to the formation of mature lamellar bone in extraskeletal soft tissues, would be very useful. Unfortunately, the mechanism(s) behind HO is(are) poorly understood. The present study reviews the literature on HO and based on it, proposes that HO can be caused by a combination of inflammation and calcification. This mechanism helps to better understand current strategies to prevent and treat HO. It also shows new opportunities to improve the treatment of bone defects in orthopedic and dental procedures.

Characterization of a Magnesium Fluoride Conversion Coating on Mg-2Y-1Mn-1Zn Screws for Biomedical Applications.

MgF2-coated screws made of a Mg-2Y-1Mn-1Zn alloy, called NOVAMag® fixation screws (biotrics bioimplants AG), were tested in vitro for potential applications as biodegradable implants, and showed a controlled corrosion rate compared to non-coated screws. While previous studies regarding coated Mg-alloys have been carried out on flat sample surfaces, the present work focused on functional materials and final biomedical products. The substrates under study had a complex 3D geometry and a nearly cylindrical-shaped shaft. The corrosion rate of the samples was investigated using an electrochemical setup, especially adjusted to evaluate these types of samples, and thus, helped to improve an already patented coating process. A MgF2/MgO coating in the µm-range was characterized for the first time using complementary techniques. The coated screws revealed a smoother surface than the non-coated ones. Although the cross-section analysis revealed some fissures in the coating structure, the electrochemical studies using Hanks' salt solution demonstrated the effective role of MgF2 in retarding the alloy degradation during the initial stages of corrosion up to 24 h. The values of polarization resistance (Rp) of the coated samples extrapolated from the Nyquist plots were significantly higher than those of the non-coated samples, and impedance increased significantly over time. After 1200 s exposure, the Rp values were 1323 ± 144 Ω.cm2 for the coated samples and 1036 ± 198 Ω.cm2 for the non-coated samples, thus confirming a significant decrease in the degradation rate due to the MgF2 layer. The corrosion rates varied from 0.49 mm/y, at the beginning of the experiment, to 0.26 mm/y after 1200 s, and decreased further to 0.01 mm/y after 24 h. These results demonstrated the effectiveness of the applied MgF2 film in slowing down the corrosion of the bulk material, allowing the magnesium-alloy screws to be competitive as dental and orthopedic solutions for the biodegradable implants market.

Biodegradable open-porous scaffolds made of sintered magnesium W4 and WZ21 short fibres show biocompatibility in vitro and in long-term in vivo evaluation.

Open-porous scaffolds made of W4 and WZ21 fibres were evaluated to analyse their potential as an implant material. WZ21 scaffolds without any surface modification or coating, showed promising mechanical properties which were comparable to the W4 scaffolds tested in previous studies. Eudiometric testing results were dependent on the experimental setup, with corrosion rates differing by a factor of 3. Cytotoxicity testing of WZ21 showed sufficient cytocompatibility. The corrosion behavior of the WZ21 scaffolds in different cell culture media are indicating a selective dealloying of elements from the magnesium scaffold by different solutions. Long term in-vivo studies were using 24 W4 scaffolds and 12 WZ21 scaffolds, both implanted in rabbit femoral condyles. The condyles and important inner organs were explanted after 6, 12 and 24 weeks and analyzed. The in-vivo corrosion rate of the WZ21 scaffolds calculated by microCT-based volume loss was up to 49 times slower than the in-vitro corrosion rate based on weight loss. Intramembranous bone formation within the scaffolds of both alloys was revealed, however a low corrosion rate and formation of gas cavities at initial time points were also detected. No systemic or local toxicity could be observed. Investigations by µ-XRF did not reveal accumulation of yttrium in the neighboring tissue. In summary, the magnesium scaffold´s performance is biocompatible, but would benefit from a surface modification, such as a coating to obtain lower the initial corrosion rates, and hereby establish a promising open-porous implant material for load-bearing applications. STATEMENT OF SIGNIFICANCE: Magnesium is an ideal temporary implant material for non-load bearing applications like bigger bone defects, since it degrades in the body over time. Here we developed and tested in vitro and in a rabbit model in vivo degradable open porous scaffolds made of sintered magnesium W4 and WZ21 short fibres. These scaffolds allow the ingrowth of cells and blood vessels to promote bone healing and regeneration. Both fibre types showed in vitro sufficient cytocompatibility and proliferation rates and in vivo, no systemic toxicity could be detected. At the implantation site, intramembranous bone formation accompanied by ingrowth of supplying blood vessels within the scaffolds of both alloys could be detected.

Biodegradation of a Magnesium Alloy Fixation Screw Used in a Guided Bone Regeneration Model in Beagle Dogs.

Nowadays, the most commonly used fixation systems are non-resorbable, but new resorbable magnesium alloy fixation screws have been introduced recently. Therefore, the aim of this study was to compare the magnesium fixation screw and the commonly used non-resorbable titanium screw in an animal model. Four 3-wall defect sites were covered with collagen membranes in the mandible of twenty beagle dogs (two sites on the left and two on the right). Each membrane was fixed with either four magnesium screws or four titanium screws. Post-operative follow-up revealed the expected observations such as transient inflammation and pain. Both groups showed a good healing response, with no differences between groups. Micro-CT analysis showed no significant difference between groups in terms of BV/TV or soft tissue volume. The void volume in the magnesium fixation screw group continued to decrease on average between the different timepoints, but not significantly. Furthermore, a gradual progression of the degradation process of the magnesium screws was observed in the same group. Magnesium screws and titanium screws showed equal performance in tissue regeneration according to GBR principles. An additional advantage of magnesium screws is their resorbable nature, which eliminates the need for a second surgical step to remove the screws.

Biodegradable magnesium barrier membrane used for guided bone regeneration in dental surgery.

Barrier membranes are commonly used as part of the dental surgical technique guided bone regeneration (GBR) and are often made of resorbable collagen or non-resorbable materials such as PTFE. While collagen membranes do not provide sufficient mechanical protection of the covered bone defect, titanium reinforced membranes and non-resorbable membranes need to be removed in a second surgery. Thus, biodegradable GBR membranes made of pure magnesium might be an alternative. In this study a biodegradable pure magnesium (99.95%) membrane has been proven to have all of the necessary requirements for an optimal regenerative outcome from both a mechanical and biological perspective. After implantation, the magnesium membrane separates the regenerating bone from the overlying, faster proliferating soft tissue. During the initial healing period, the membrane maintained a barrier function and space provision, whilst retaining the positioning of the bone graft material within the defect space. As the magnesium metal corroded, it formed a salty corrosion layer and local gas cavities, both of which extended the functional lifespan of the membrane barrier capabilities. During the resorption of the magnesium metal and magnesium salts, it was observed that the membrane became surrounded and then replaced by new bone. After the membrane had completely resorbed, only healthy tissue remained. The in vivo performance study demonstrated that the magnesium membrane has a comparable healing response and tissue regeneration to that of a resorbable collagen membrane. Overall, the magnesium membrane demonstrated all of the ideal qualities for a barrier membrane used in GBR treatment.

Biodegradable magnesium fixation screw for barrier membranes used in guided bone regeneration.

An ideal fixation system for guided bone (GBR) regeneration in oral surgery must fulfil several criteria that includes the provision of adequate mechanical fixation, complete resorption when no longer needed, complete replacement by bone, as well as be biocompatible and have a good clinical manageability. For the first time, a biodegradable magnesium fixation screw made of the magnesium alloy WZM211 with a MgF2 coating has been designed and tested to fulfill these criteria. Adequate mechanical fixation was shown for the magnesium fixation screw in several benchtop tests that directly compared the magnesium fixation screw with an equivalent polymeric resorbable device. Results demonstrated slightly superior mechanical properties of the magnesium device in comparison to the polymeric device even after 4 weeks of degradation. Biocompatibility of the magnesium fixation screw was demonstrated in several in vitro and in vivo tests. Degradation of the magnesium screw was investigated in in vitro and in vivo tests, where it was found that the screw is resorbed slowly and completely after 52 weeks, providing adequate fixation in the early critical healing phase. Overall, the magnesium fixation screw demonstrates all of the key properties required for an ideal fixation screw of membranes used in guided bone regeneration (GBR) surgeries.

Action potentials in primary osteoblasts and in the MG-63 osteoblast-like cell line.

Whole-cell patch-clamp analysis revealed a resting membrane potential of -60 mV in primary osteoblasts and in the MG-63 osteoblast-like cells. Depolarization-induced action potentials were characterized by duration of 60 ms, a minimal peak-to-peak distance of 180 ms, a threshold value of -20 mV and a repolarization between the spikes to -45 mV. Expressed channels were characterized by application of voltage pulses between -150 mV and 90 mV in 10 mV steps, from a holding potential of -40 mV. Voltages below -60 mV induced an inward current. Depolarizing voltages above -30 mV evoked two currents: (a) a fast activated and inactivated inward current at voltages between -30 and 30 mV, and (b) a delayed-activated outward current that was induced by voltages above -30 mV. Electrophysiological and pharmacological parameters indicated that hyperpolarization activated strongly rectifying K(+) (K(ir)) channels, whereas depolarization activated tetrodotoxin sensitive voltage gated Na(+) (Na(v)) channels as well as delayed, slowly activated, non-inactivating, and tetraethylammonium sensitive voltage gated K(+) (K(v)) channels. In addition, RT-PCR showed expression of Na(v)1.3, Na(v)1.4, Na(v)1.5, Na(v)1.6, Na(v)1.7, and K(ir)2.1, K(ir)2.3, and K(ir)2.4 as well as K(v)2.1. We conclude that osteoblasts express channels that allow firing of action potentials.

Mesenchymal stem cell-dependent formation of heterotopic tendon-bone insertions (osteotendinous junctions).

Ligament-to-bone and tendon-to-bone interfaces (entheses, osteotendinous junctions [OTJs]) serve to dissipate stress between soft tissue and bone. Surgical reconstruction of these interfaces is an issue of considerable importance as they are prone to injury and the integration of bone and tendon/ligament is in general not satisfactory. We report here the stem cell-dependent spontaneous formation of fibrocartilaginous and fibrous entheses in heterotopic locations of the mouse if progenitors possess a tenogenic and osteo-/chondrogenic capacity. This study followed the hypothesis that enhanced Bone Morphogenetic Protein (BMP)-signaling in adult mesenchymal stem cells that are induced for tendon formation may overcome the tendon-inherent interference with bone formation and may thus allow the stem cell-dependent formation of tendon-bone interfaces. The tenogenic and osteo-/chondrogenic competence was mediated by the adeno- and/or lentiviral expression of the biologically active Smad8 signaling mediator (Smad8ca) and of Bone Morphogenetic Protein 2 (BMP2). Modified mesenchymal progenitors were implanted in subcutaneous or intramuscular sites of the mouse. The stem cell-dependent enthesis formation was characterized histologically by immunohistological approaches and by in situ hybridization. Transplantation of modified murine stem cells resulted in the formation of tendinous and osseous structures exhibiting fibrocartilage-type OTJs, while, in contrast, the viral modification of primary human bone marrow-derived mesenchymal stromal/stem cells showed evidence of fibrous tendon-bone interface formation. Moreover, it could be demonstrated that Smad8ca expression alone was sufficient for the formation of tendon/ligament-like structures. These findings may contribute to the establishment of stem cell-dependent regenerative therapies involving tendon/ligaments and to the improvement of the insertion of tendon grafts at bony attachment sites, eventually.

Coating of titanium implants with copolymer supports bone regeneration: a comparative in vivo study in rabbits.

PURPOSE: In modern orthopedics aseptic loosening caused by the formation of micro-wear particles remains a problem for endoprosthetic joint replacements as revision surgery is necessary with corresponding costs and exertions by patients. This study is devoted to the question of how the osseous ingrowth of implants can be supported. It was investigated whether the developed copolymer, p-VBP-co-GMA, coated on the surface of the implants, supports bone healing. In addition, it was analyzed whether covalent linkage of Bone Morphogenetic Protein 2 (BMP-2) to the copolymer layer enhances bone formation. METHODS: Eight adult New Zealand White Rabbits were implanted with four different foils (control, copolymer, copolymer + BMP-2, control + BMP-2) each. The histomorphometric analysis of all samples was made 28 days after implantation. RESULTS: The copolymer had a positive effect on bone remodeling compared to the control group. We observed that the copolymer group had a significantly increased bone volume per tissue volume ratio and bone density to the control group. In contrast, this in-vivo study showed that the immobilization of BMP-2 onto the copolymer layer did not enhance bone healing. The bone volume per tissue volume ratio was decreased as well as the bone density compared to control + BMP-2 group. CONCLUSION: The analysis showed that the bone remodeling process in the copolymer + BMP-2-group is in an early phase comparable to the control group. These results suggest that the coating with the developed copolymer has major potential for medical use as it enhances bone mass around the implant.

Multi-scale mechanical and morphological characterisation of sintered porous magnesium-based scaffolds for bone regeneration in critical-sized defects.

Magnesium (Mg) and its alloys are very promising degradable, osteoconductive and osteopromotive materials to be used as regenerative treatment for critical-sized bone defects. Under load-bearing conditions, Mg alloys must display sufficient morphological and mechanical resemblance to the native bone they are meant to replace to provide adequate support and enable initial bone bridging. In this study, unique highly open-porous Mg-based scaffolds were mechanically and morphologically characterised at different scales. In situ X-ray computed tomography (XCT) mechanics, digital volume correlation (DVC), electron microscopy and nanoindentation were combined to assess the influence of material properties on the apparent (macro) mechanics of the scaffold. The results showed that Mg exhibited a higher connected structure (38.4mm-3 and 6.2mm-3 for Mg and trabecular bone (Tb), respectively) and smaller spacing (245µm and 629µm for Mg and Tb, respectively) while keeping an overall appropriate porosity of 55% in the range of trabecular bone (30-80%). This fully connected and highly porous structure promoted lower local strain compared to the trabecular bone structure at material level (i.e. -22067 ± 8409µÎµ and -40120 ± 18364µÎµ at 6% compression for Mg and trabecular bone, respectively) and highly ductile mechanical behaviour at apparent level preventing premature scaffold failure. Furthermore, the Mg scaffolds exceeded the physiological strain of bone tissue generated in daily activities such as walking or running (500-2000µÎµ) by one order of magnitude. The yield stress was also found to be close to trabecular bone (2.06MPa and 6.67MPa for Mg and Tb, respectively). Based on this evidence, the study highlights the overall biomechanical suitability of an innovative Mg-based scaffold design to be used as a treatment for bone critical-sized defects. STATEMENT OF SIGNIFICANCE: Bone regeneration remains a challenging field of research where different materials and solutions are investigated. Among the variety of treatments, biodegradable magnesium-based implants represent a very promising possibility. The novelty of this study is based on the characterisation of innovative magnesium-based implants whose structure and manufacturing have been optimised to enable the preservation of mechanical integrity and resemble bone microarchitecture. It is also based on a multi-scale approach by coupling high-resolution X-ray computed tomography (XCT), with in situ mechanics, digital volume correlation (DVC) as well as nano-indentation and electron-based microscopy imaging to define how degradable porous Mg-based implants fulfil morphological and mechanical requirements to be used as critical bone defects regeneration treatment.