Challenges and Pitfalls of Research Designs Involving Magnesium-Based Biomaterials: An Overview.

Magnesium-based biomaterials hold remarkable promise for various clinical applications, offering advantages such as reduced stress-shielding and enhanced bone strengthening and vascular remodeling compared to traditional materials. However, ensuring the quality of preclinical research is crucial for the development of these implants. To achieve implant success, an understanding of the cellular responses post-implantation, proper model selection, and good study design are crucial. There are several challenges to reaching a safe and effective translation of laboratory findings into clinical practice. The utilization of Mg-based biomedical devices eliminates the need for biomaterial removal surgery post-healing and mitigates adverse effects associated with permanent biomaterial implantation. However, the high corrosion rate of Mg-based implants poses challenges such as unexpected degradation, structural failure, hydrogen evolution, alkalization, and cytotoxicity. The biocompatibility and degradability of materials based on magnesium have been studied by many researchers in vitro; however, evaluations addressing the impact of the material in vivo still need to be improved. Several animal models, including rats, rabbits, dogs, and pigs, have been explored to assess the potential of magnesium-based materials. Moreover, strategies such as alloying and coating have been identified to enhance the degradation rate of magnesium-based materials in vivo to transform these challenges into opportunities. This review aims to explore the utilization of Mg implants across various biomedical applications within cellular (in vitro) and animal (in vivo) models.

Osteosynthesis-associated infection in maxillofacial surgery by bacterial biofilms: a retrospective cohort study of 11 years.

OBJECTIVES: The aim of this retrospective cohort study was to determine risk factors for osteosynthesis-associated infections (OAI) with subsequent necessity of implant removal in oral and maxillofacial surgery. MATERIALS AND METHODS: A total of 3937 records of patients who received either orthognathic, trauma, or reconstructive jaw surgery from 2009 to 2021 were screened for osteosynthetic material removal due to infection. Treatment-intervals, volume of applied osteosynthetic material, and respective surgical procedures were also assessed. Moreover, intraoperatively harvested microbial flora was cultured and subsequently identified by MALDI TOF. Bacteria were then screened for antibiotic resistance via VITEK system or, if necessary, via agar diffusion or epsilometer test. Data was analyzed utilizing SPSS statistical software. For statistical analysis of categorical variables, chi-square tests or Fisher exact tests were used. Continuous variables were compared via non-parametric tests. The level of significance for p-values was set at < 0.05. Descriptive analysis was also performed. RESULTS: The lower jaw was more prone to OAI than the mid face region. Larger volumes of osteosynthetic material led to significantly more OAI, resulting in reconstruction plates bearing the highest risk for OAI especially when compared to small-volume mini-plates frequently applied in trauma surgery. Among OAI associated with implant volumes smaller than 1500 mm3, the detection of Streptococcus spp., Prevotella spp., Staphylococcus spp., and Veillonella spp. was significantly elevated, whereas implant volumes larger than 1500 mm3 showed a significant increase of Enterococcus faecalis, Proteus mirabilis and Pseudomonas aeruginosa. High susceptibility rates (87.7-95.7%) were documented for 2nd- and 3rd-generation cephalosporines and piperacillin/tazobactam. CONCLUSION: High material load and lower jaw reconstruction bear the greatest risks for OAI. When working with large volume osteosynthetic implants, gram-negative pathogens must be considered when choosing an appropriate antibiotic regime. Suitable antibiotics include, e.g., piperacillin/tazobactam and 3rd-generation cephalosporines. CLINICAL RELEVANCE: Osteosynthetic material utilized in reconstructive procedures of the lower jaw may be colonized with drug-resistant biofilms.

Outcomes of the Nonendoscopic Transoral Approach to Subcondylar Mandible Fractures.

PURPOSE: The transoral approach (TRA) to subcondylar fractures without any endoscopic or transbuccal assistance is not a common technique. The purpose of this study was to measure and compare the quality of open reduction and internal fixation (ORIF) between the TRA and the retromandibular approach (RMB), including types and frequencies of postoperative complications. METHODS: In our retrospective cohort study, we enrolled a sample of patients with displaced subcondylar mandible fractures treated by ORIF. The predictor was the approach mode: TRA or RMB. In postoperative computed tomography (CT) data sets, we measured the angles of the condylar process in relation to references: 1) midline, 2) lateral ramus border, and 3) posterior ramus border. The primary outcome variable was the reduction outcome, which was calculated as the difference between the total of all angles of the operated side and the non-affected side. Secondary outcomes were postoperative complications extracted from patients' files. Other variables were age, gender, number of plates, operation time and a modified AO trauma score. In bivariate analysis, we compared the outcome between both groups. RESULTS: Sixty-four patients were included in total, with TRA performed in 50%. Patients with TRA were younger (31 vs 41, P = .003), and the trauma score was lower (1.9 vs 3.3, P < .001). Reduction outcome remained comparable between both techniques (mean 3.7° for both, P = .92). Complication rates were similar, although facial nerve palsy was absent for TRA (0 vs 4, P = .039). CONCLUSION: We suggest TRA for selected patients with displaced, single fragmented subcondylar fractures. Reduction outcome shows a comparable exactness to RMB, while TRA is safer for the facial nerve.

The Benefits of Fibrinolysis Combined with Venous Systemic Oxygen Persufflation (VSOP) in a Rat Model of Donation after Circulatory Death and Orthotopic Liver Transplantation.

Organ shortage has led to the increasing utilization of livers retrieved from donors after circulatory death (DCD). These pre-damaged organs are susceptible to further warm ischemia and exhibit minimal tolerance for cold storage. The aim was thus to examine the effects of fibrinolysis combined with Venous Systemic Oxygen Persufflation (VSOP) on the preservation of DCD livers in vivo. Livers of male Lewis rats were explanted after 45 min of warm ischemia, cold-stored for 18 h, and transplanted into a recipient animal. Livers were left untreated or underwent either VSOP or fibrinolysis via Streptokinase (SK) or received combined SK and VSOP. Combined treatment exhibited improved microvascular flow at 168 h (p = 0.0009) and elevated microperfusion velocity at 24 h post-transplantation (p = 0.0007). Combination treatment demonstrated increased portal venous flow (PVF) at 3 and 24 h post-transplantation (p = 0.0004, p < 0.0001), although SK and VSOP analogously achieved increases at 24 h (p = 0.0036, p = 0.0051). Enzyme release was decreased for combination treatment (p = 0.0002, p = 0.0223) and lactate dehydrogenase (LDH) measurements were lower at 24 h post-transplantation (p = 0.0287). Further supporting findings have been obtained in terms of serum cytokine levels and in the alterations of endothelial injury markers. The combination treatment of SK + VSOP might provide improved organ integrity and viability and may therefore warrant further investigation as a potential therapeutic approach in the clinical setting of DCD.

Influence of the Casting Concentration on the Mechanical and Optical Properties of FA/CaCl2-Derived Silk Fibroin Membranes.

In this study, we describe the manufacturing and characterization of silk fibroin membranes derived from the silkworm Bombyx mori. To date, the dissolution process used in this study has only been researched to a limited extent, although it entails various potential advantages, such as reduced expenses and the absence of toxic chemicals in comparison to other conventional techniques. Therefore, the aim of this study was to determine the influence of different fibroin concentrations on the process output and resulting membrane properties. Casted membranes were thus characterized with regard to their mechanical, structural and optical assets via tensile testing, SEM, light microscopy and spectrophotometry. Cytotoxicity was evaluated using BrdU, XTT, and LDH assays, followed by live-dead staining. The formic acid (FA) dissolution method was proven to be suitable for the manufacturing of transparent and mechanically stable membranes. The fibroin concentration affects both thickness and transparency of the membranes. The membranes did not exhibit any signs of cytotoxicity. When compared to other current scientific and technical benchmarks, the manufactured membranes displayed promising potential for various biomedical applications. Further research is nevertheless necessary to improve reproducible manufacturing, including a more uniform thickness, less impurity and physiological pH within the membranes.

Combined severe plastic deformation processing of commercial purity titanium enables superior fatigue resistance for next generation implants.

Commercial purity titanium (cp-Ti) is considered for replacing Ti64 as an implant material in various applications, due to the potential toxicity associated with the release of Al and V ions. However, the mechanical properties of cp-Ti, particularly fatigue resistance, are inadequate for this purpose. In this study, cp-Ti grade 4 rods were processed using a combination of equal channel angular pressing and rotary swaging (ECAP/RS). Tensile and fatigue tests were conducted, along with detailed microscopy and evaluation of corrosion resistance and biocompatibility. An average yield strength of 1383 MPa was obtained while maintaining moderate ductility of 10 %. This represents the highest strength ever recorded for cp-Ti, even exceeding that of Ti64. Additionally, fatigue endurance limit increased by 43 % up to 600 MPa, almost obtaining that of Ti64. Strengthening mechanisms were attributed to the ultrafine-grained (UFG) microstructure generated by ECAP/RS, along with strong crystallographic texture and formation of sub-grain structure. Furthermore, the corrosion resistance and biocompatibility of cp-Ti were largely unaffected, potentially easing regulatory transition in future medical devices. Thus, these results demonstrate high potential of combined ECAP/RS processing to manufacture UFG cp-Ti grade 4 materials that prospectively allow for the substitution of questionable alloys and downsizing of medical implants.

An Overview of Scaffolds and Biomaterials for Skin Expansion and Soft Tissue Regeneration: Insights on Zinc and Magnesium as New Potential Key Elements.

The utilization of materials in medical implants, serving as substitutes for non-functional biological structures, supporting damaged tissues, or reinforcing active organs, holds significant importance in modern healthcare, positively impacting the quality of life for millions of individuals worldwide. However, certain implants may only be required temporarily to aid in the healing process of diseased or injured tissues and tissue expansion. Biodegradable metals, including zinc (Zn), magnesium (Mg), iron, and others, present a new paradigm in the realm of implant materials. Ongoing research focuses on developing optimized materials that meet medical standards, encompassing controllable corrosion rates, sustained mechanical stability, and favorable biocompatibility. Achieving these objectives involves refining alloy compositions and tailoring processing techniques to carefully control microstructures and mechanical properties. Among the materials under investigation, Mg- and Zn-based biodegradable materials and their alloys demonstrate the ability to provide necessary support during tissue regeneration while gradually degrading over time. Furthermore, as essential elements in the human body, Mg and Zn offer additional benefits, including promoting wound healing, facilitating cell growth, and participating in gene generation while interacting with various vital biological functions. This review provides an overview of the physiological function and significance for human health of Mg and Zn and their usage as implants in tissue regeneration using tissue scaffolds. The scaffold qualities, such as biodegradation, mechanical characteristics, and biocompatibility, are also discussed.

Evolution from Bioinert to Bioresorbable: In Vivo Comparative Study of Additively Manufactured Metal Bone Scaffolds.

Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most successful orthopedic material - have yet to yield satisfactory results. Conventional bio-inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non-bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L-PBF) technology. This in vivo study presents a comprehensive, side-by-side comparative analysis of the interactions between bone regeneration and additively manufactured bio-inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in-depth understanding of the metal scaffold-assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Long-term in vivo observations show biocompatibility and performance of ZX00 magnesium screws surface-modified by plasma-electrolytic oxidation in Göttingen miniature pigs.

Bioabsorbable magnesium implants for orthopedic fixation of bone have recently become available for different fields of indication. While general questions of biocompatibility have been answered, tailoring suitable degradation kinetics for specific applications as well as long-term tissue integration remain the focus of current research. The aim of this study was the evaluation of the long-term degradation behavior and osseointegration of Mg-Ca-Zn (ZX00MEO) based magnesium implants with plasma-electrolytic oxidation (PEO) surface modification (ZX00MEO-PEO) in comparison to non-surface modified implants in vivo and in vitro. Besides a general evaluation of the biological performance of the alloy over a prolonged period, the main hypothesis was that PEO surface modification significantly reduces implant degradation rate and improves tissue interaction. In vitro, the microstructure and surface of the bioabsorbable screws were characterized by SEM/EDS, cytocompatibility and degradation testing facilitating hydrogen gas evolution, carried out following ISO 10993-5/-12 and ASTM F3268-18a/ASTM G1-03 (E1:2017). In vivo, screws were implanted in the frontal bone of Minipigs for 6, 12, and 18 months, following radiological and histomorphometric analysis. A slower and more uniform degradation and improved cytocompatibility could be shown for the ZX00MEO-PEO group in vitro. A significant reduction of degradation rate and enhanced bone formation around the ZX00MEO-PEO screws in vivo was confirmed. Proficient biocompatibility and tissue integration could generally be shown in vivo regardless of surface state. The tested magnesium alloy shows generally beneficial properties as an implant material, while PEO-surface modification further improves the bioabsorption behavior both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Devices from bioabsorbable Magnesium have recently been introduced to orthopedic applications. However, the vast degradation of Magnesium within the human body still gives limitations. While reliable in-vivo data on most promising surface treatments such as Plasma-electrolytic-Oxidation is generally scarce, long-time results in large animals are to this date completely missing. To overcome this lack of evidence, we studied a Magnesium-Calzium-Zinc-alloy with surface enhancement by PEO for the first time ever over a period of 18 months in a large animal model. In-vitro, surface-modified screws showed significantly improved cytocompatibility and reduction of degradation confirmed by hydrogen gas evolution testing, while in-vivo radiological and histological evaluation generally showed good biocompatibility and bioabsorption as well as significantly enhanced reduction of degradation and faster bone regeneration in the PEO-surface-modified group.

Development and validation of a parametric human mandible model to determine internal stresses for the future design optimization of maxillofacial implants.

Large segmental mandible bone defects still represent a challenge for endogenous regeneration. Despite the bone's capacity to heal in many clinical situations, bone defects over a critical size do not heal spontaneously. An emerging treatment of critically sized mandibular defects is the implantation of individually manufactured scaffolds consisting of biodegradable magnesium alloys. Biomedical engineers faced the challenge of developing a scaffold structure that not only provides sufficient stability, but also stimulates and promotes bone growth while considering the degradation of the magnesium alloy. The porosity of the scaffold must also support bone ingrowth and neovascularization. For an optimal design and subsequent structural optimization knowledge of external load cases is essential. However, currently the muscle and joint forces of the mandible cannot be measured directly. The aim of our study was therefore the development of a parametric human mandible model to determine the relevant boundary conditions for the subsequent structural optimization of individual jawbone implants. Using a model-based approach, determining the essential external load of the mandible as a function of the age and sex of a patient individually and the realistic simulation of the mechanical stress for patient-specific loads and anatomies has been realized. The developed model is successfully validated by evaluating the deformations and stresses of the lower jaw of a possible patient and comparing them with the results of dental research. Based on the results of the modelling, in a subsequent optimization process section forces at the interface between the bone tissue and jawbone implant can be determined and used to optimize the design of the jawbone implant.

Antibacterial properties of functionalized silk fibroin and sericin membranes for wound healing applications in oral and maxillofacial surgery.

Oral wounds are among the most troublesome injuries which easily affect the patients' quality of life. To date, the development of functional antibacterial dressings for oral wound healing remains a challenge. In this regard, we investigated antibacterial silk protein-based membranes for the application as wound dressings in oral and maxillofacial surgery. The present study includes five variants of casted membranes, i.e., i) membranes-silver nanoparticles (CM-Ag), ii) membranes-gentamicin (CM-G), iii) membranes-control (without functionalization) (CM-C), iv) membranes-silk sericin control (CM-SSC), and v) membranes-silk fibroin/silk sericin (CM-SF/SS), and three variants of nonwovens, i.e., i) silver nanoparticles (NW-Ag), ii) gentamicin (NW-G), iii) control (without functionalization) (NW-C). The surface structure of the samples was visualized with scanning electron microscopy. In addition, antibacterial testing was accomplished using agar diffusion assay, colony forming unit (CFU) analysis, and qrt-PCR. Following antibacterial assays, biocompatibility was evaluated by cell proliferation assay (XTT), cytotoxicity assay (LDH), and live-dead assay on L929 mouse fibroblasts. Findings indicated significantly lower bacterial colony growth and DNA counts for CM-Ag with a reduction of bacterial counts by 3log levels (99.9% reduction) in CFU and qrt-PCR assay compared to untreated control membranes (CM-C and CM-SSC) and membranes functionalized with gentamicin (CM-G and NW-G) (p < 0.001). Similarly, NW-G yielded significantly lower DNA and colony growth counts compared to NW-Ag and NW-C (p < 0.001). In conclusion, CM-Ag represented 1log level better antibacterial activity compared to NW-G, whereas NW-G showed better cytocompatibility for L929 cells. As data suggest, these two membranes have the potential of application in the field of bacteria-free oral wound healing. However, provided that loading strategy and cytocompatibility are adjusted according to the antibacterial agents' characteristic and fabrication technique of the membranes.

Preoperative Perforator Mapping in DIEP Flaps for Breast Reconstruction. The Impact of New Contrast-Enhanced Ultrasound Techniques.

Deep inferior epigastric artery flaps (DIEP) represent the gold standard of autologous breast reconstruction. Due to significant variations in vascular anatomy, preoperative perforator mapping (PM) is mandatory in order to ensure the presence of a sufficient perforator within the flap. In this regard, CT angiography (CTA) is currently the method of choice. Therefore, we investigated the value of contrast-enhanced ultrasound (CEUS) techniques for preoperative PM in comparison to CTA. Patients underwent PM, utilizing both CTA and CEUS techniques. Documentation included the course of the vascular pedicle through the rectus muscle (M), fascial penetration (F), the subcutaneous plexus (P) and the skin point (SP) on either side of the abdomen. Thus, contrast-enhanced B-Flow (BCEUS), B-Flow ultrasound (BUS), CEUS, color Doppler ultrasound (CDUS) and CTA were evaluated in terms of the diagnostic consistency and effectiveness of PM. Precision (∆L) was then calculated in relation to the actual intraoperative location. Statistical analysis included Kruskall-Wallis, Levene and Bonferroni tests, as well as Spearman correlations. A total of 39 DIEP flaps were analyzed. Only CTA (∆L = 2.85 mm) and BCEUS (∆L = 4.57 mm) enabled complete PM, also including P and SP, whereas CDUS, CEUS and BUS enabled clear PM throughout M and F only. Regarding the number of detected perforators, PM techniques are ranked from high to low as follows: CTA, BCEUS, BUS, CEUS and CDUS. CTA and BCEUS showed sufficient diagnostic consistency for SP, P and F, while CDUS and CTA had a superior performance for M. BCEUS offers precise image-controlled surface tags and dynamic information for PM without imposing radiation and may, therefore, be considered a feasible add-on or alternative to CTA. However, BCEUS requires an experienced examiner and is more time-consuming.

Microstructure, mechanical properties, corrosion resistance and cytocompatibility of WE43 Mg alloy scaffolds fabricated by laser powder bed fusion for biomedical applications.

Open-porous scaffolds of WE43 Mg alloy with a body-center cubic cell pattern were manufactured by laser powder bed fusion with different strut diameters. The geometry of the unit cells was adequately reproduced during additive manufacturing and the porosity within the struts was minimized. The microstructure of the scaffolds was modified by means of thermal solution and ageing heat treatments and was analysed in detail by means of X-ray microtomography, optical, scanning and transmission electron microscopy. Moreover, the corrosion rates and the mechanical properties of the scaffolds were measured as a function of the strut diameter and metallurgical condition. The microstructure of the as-printed scaffolds contained a mixture of Y-rich oxide particles and Rare Earth-rich intermetallic precipitates. The latter could be modified by heat treatments. The lowest corrosion rates of 2-3 mm/year were found in the as-printed and solution treated scaffolds and they could be reduced to ~0.1 mm/year by surface treatments using plasma electrolytic oxidation. The mechanical properties of the scaffolds improved with the strut diameter: the yield strength increased from 8 to 40 MPa and the elastic modulus improved from 0.2 to 0.8 GPa when the strut diameter increased from 275 µm to 800 µm. Nevertheless, the strength of the scaffolds without plasma electrolytic oxidation treatment decreased rapidly when immersed in simulated body fluid. In vitro bicompatibility tests showed surface treatments by plasma electrolytic oxidation were necessary to ensure cell proliferation in scaffolds with high surface-to-volume ratio.

Towards a flexible electrochemical biosensor fabricated from biocompatible Bombyx mori silk.

In modern days, there is an increasing relevance of and demand for flexible and biocompatible sensors for in-vivo and epidermal applications. One promising strategy is the implementation of biological (natural) polymers, which offer new opportunities for flexible biosensor devices due to their high biocompatibility and adjustable biodegradability. As a proof-of-concept experiment, a biosensor was fabricated by combining thin- (for Pt working- and counter electrode) and thick-film (for Ag/AgCl quasi-reference electrode) technologies: The biosensor consists of a fully bio-based and biodegradable fibroin substrate derived from silk fibroin of the silkworm Bombyx mori combined with immobilized enzyme glucose oxidase. The flexible glucose biosensor is encapsulated by a biocompatible silicon rubber which is certificated for a safe use onto human skin. Characterization of the sensor set-up is exemplarily demonstrated by glucose measurements in buffer and Ringer's solution, while the stability of the quasi-reference electrode has been investigated versus a commercial Ag/AgCl reference electrode. Repeated bending studies validated the mechanical properties of the electrode structures. The cross-sensitivity of the biosensor against ascorbic acid, noradrenaline and adrenaline was investigated, too. Additionally, biocompatibility and degradation tests of the silk fibroin with and without thin-film platinum electrodes were carried out.

An Innovative Approach for Preoperative Perforator Flap Planning Using Contrast-enhanced B-flow Imaging.

Precise perforator mapping of the epifascial and subcutaneous course of the perforator flaps, including the precise detection of the skin point, is mandatory for successful preoperative flap design and planning of supramicrosurgery. We investigated the effectiveness of contrast-enhanced B-flow (BCEUS) imaging for perforator mapping and preoperative perforator flap planning and compared it with B-flow ultrasound, contrast-enhanced ultrasound, and color Doppler ultrasound. Sixteen patients who received an individualized perforator flap reconstruction were included in the study. Preoperative perforator mapping includes the following structures: subfascial course of the pedicle, fascial penetration point, subcutaneous course (epifascial and subcutaneous), and perforator skin point. The precision of the preoperative perforator mapping was analyzed for color Doppler ultrasound, contrast-enhanced ultrasound, B-flow ultrasound, and BCEUS. Each technique was able to precisely display the subfascial course of the vascular pedicle, including the fascial penetration point. However, only BCEUS enabled precise mapping of the epifascial and subcutaneous (suprafascial) course, including the skin point of the perforators with a clear delineation. Precise knowledge of the suprafascial course of the perforators is mandatory for successful supermicrosurgery and perforator flap planning. BCEUS imaging facilitates full perforator mapping, which improves the safety of flap harvesting. However, BCEUS is technically demanding and requires an experienced sonographer.

A novel titanium implant surface modification by plasma electrolytic oxidation (PEO) preventing tendon adhesion.

Titanium is one of the most commonly used materials for implants in trauma applications due to its low density, high corrosion resistance and biocompatibility. Nevertheless, there is still a need for improved surface modifications of Titanium, in order to change surface properties such as wettability, antibacterial properties or tissue attachment. In this study, different novel plasma electrolytic oxidation (PEO) modifications have been investigated for tendon adhesion to implants commonly used in hand surgery. Titanium samples with four different PEO modifications were prepared by varying the electrolyte composition and analyzed with regards to their surface properties. Unmodified titanium blanks and Dotize® coating served as controls. Samples were examined using scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), contact angle measuring system and analyzed for their biocompatibility and hemocompatibility (according to DIN ISO 10993-5 and 10,993-4). Finally, tendon adhesion of these specific surfaces were investigated by pull-off tests. Our findings show that surface thickness of PEO modifications was about 12-20 µm and had porous morphology. One modification demonstrated hydrophilic behavior accompanied by good biocompatibility without showing cytotoxic properties. Furthermore, no hemolytic effect and no significant influence on hemocompatibility were observed. Pull-off tests revealed a significant reduction of tendon adhesion by 64.3% (35.7% residual adhesion), compared to unmodified titanium (100%). In summary, the novel PEO-based ceramic-like porous modification for titanium surfaces might be considered a good candidate for orthopedic applications supporting a more efficient recovery.

Improved in vivo osseointegration and degradation behavior of PEO surface-modified WE43 magnesium plates and screws after 6 and 12 months.

Magnesium is a highly promising candidate with respect to its future use as a material for resorbable implants. When magnesium degrades, hydrogen gas is released. High doses of gas emergence are reported to impair osseointegration and may therefore lead to fixation failure. The successful delay and reduction of the degradation rate by applying plasma electrolytic oxidation (PEO) as a post processing surface modification method for magnesium alloy has recently been demonstrated. The aim of this study was thus to compare the degradation behavior of a WE43-based plate system with and without respective PEO surface modification and to further investigate osseointegration, as well as the resulting effects on the surrounding bony tissue of both variants in a miniature pig model. WE43 magnesium screws and plates without (WE43) and with PEO surface modification (WE43-PEO) were implanted in long bones of Göttingen Miniature Pigs. At six and twelve months after surgery, micro-CT and histomorphometric analysis was performed. Residual screw volume (SV/TV; WE43: 28.8 ± 21.1%; WE43-PEO: 62.9 ± 31.0%; p = 0.027) and bone implant contact area (BIC; WE43: 18.1 ± 21.7%; WE43-PEO: 51.6 ± 27.7%; p = 0.015) were increased after six months among the PEO-modified implants. Also, surrounding bone density within the cortical bone was not affected by surface modification (BVTV; WE43: 76.7 ± 13.1%; WE43-PEO: 73.1 ± 16.2%; p = 0.732). Intramedullar (BV/TV; WE43: 33.2 ± 16.7%; WE43-PEO 18.4 ± 9.0%; p = 0.047) and subperiosteal (bone area; WE43: 2.6 ± 3.4 mm2; WE43-PEO: 6,9 ± 5.2 mm2; p = 0.049) new bone formation was found for both, surface-modified and non-surface-modified groups. After twelve months, no significant differences of SV/TV and BV/TV were found between the two groups. PEO surface modification of WE43 plate systems improved osseointegration and significantly reduced the degradation rate within the first six months in vivo. Osteoconductive and osteogenic stimulation by WE43 magnesium implants led to overall increased bone growth, when prior PEO surface modification was conducted.

Influence of surface condition on the degradation behaviour and biocompatibility of additively manufactured WE43.

The further development of future Magnesium based biodegradable implants must consider not only the freedom of design, but also comprise implant volume reduction, as both aspects are crucial for the development of higher functionalised implants, such as plate systems or scaffold grafts in bone replacement therapy. As conventional manufacturing methods such as turning and milling are often accompanied by limitations concerning implant design and functionality, the process of laser powder bed fusion (LPBF) specifically for Magnesium alloys was recently introduced. In addition, the control of the degradation rate remains a key aspect regarding biodegradable implants. Recent studies focusing on the degradation behaviour of additively manufactured Magnesium scaffolds disclosed additional intricacies when compared to conventionally manufactured Magnesium parts, as a notably larger surface area was exposed to the immersion medium and scaffold struts degraded non-uniformly. Moreover, chemical etching as post processing technique is applied to remove sintered powder particles from the surface, altering surface chemistry. In this study, cylindrical Magnesium specimens were manufactured by LPBF and surfaces were consecutively modified by phosphoric etching and machining. Degradation behaviour and biocompatibility were then investigated, revealing that etched samples exhibited the overall lowest degradation rates, but experienced large pit formation, while the reduction of surface roughness resulted in a delay of degradation.

Effect of process parameters on additive-free electrospinning of regenerated silk fibroin nonwovens.

Silk fibroin is a biomaterial with multiple beneficial properties for use in regenerative medicine and tissue engineering. When dissolving and processing the reconstituted silk fibroin solution by electrospinning, the arrangement and size of fibers can be manifold varied and according fiber diameters reduced to the nanometer range. Such nonwovens show high porosity as well as potential biocompatibility. Usually, electrospinning of most biomaterials demands for the application of additives, which enable stable electrospinning by adjusting viscosity, and are intended to evaporate during processing or to be washed out afterwards. However, the use of such additives increases costs and has to be taken into account in terms of biological risks when used for biomedical applications. In this study, we explored the possibilities of additive-free electrospinning of pure fibroin nonwovens and tried to optimize process parameters to enable stable processing. We used natural silk derived from the mulberry silkworm Bombyx mori. After degumming, the silk fibroin was dissolved and the viscosity of the spinning solution was controlled by partial evaporation of the initial solving agent. This way, we were able to completely avoid the use of additives and manufacture nonwovens, which potentially offer higher biocompatibility and reduced immunogenicity. Temperature and relative humidity during electrospinning were systematically varied (25-35 °C, 25-30% RH). In a second step, the nonwovens optionally underwent methanol treatment to initiate beta-sheet formation in order to increase structural integrity and strength. Comprehensive surface analysis on the different nonwovens was performed using scanning electron microscopy and supplemented by additional mechanical testing. Cytotoxicity was evaluated using BrdU-assay, XTT-assay, LDH-assay and live-dead staining. Our findings were, that an increase of temperature and relative humidity led to unequal fiber diameters and defective nonwovens. Resistance to penetration decreased accordingly. The most uniform fiber diameters of 998 ± 63 nm were obtained at 30 °C and 25% relative humidity, also showing the highest value for resistance to penetration (0.20 N). The according pure fibroin nonwoven also showed no signs of cytotoxicity. However, while the biological response showed statistical evidence, the material characteristics showed no statistically significant correlation to changes of the ambient conditions within the investigated ranges. We suggest that further experiments should explore additional ranges for temperature and humidity and further focus on the repeatability of material properties in dependency of suitable process windows.

Influence of design and postprocessing parameters on the degradation behavior and mechanical properties of additively manufactured magnesium scaffolds.

Magnesium shows promising properties concerning its use in absorbable implant applications such as biodegradability, improved mechanical strength and plastic deformability. Following extensive research, the first fixation and compression screws composed of magnesium rare earth alloys were commercialised, notably in the field of orthopaedic surgery. Preclinical and clinical follow-up studies showed that the rapid degradation of unprotected metallic Magnesium surfaces and concomitant hydrogen gas bursts still raise concern regarding certain surgical indications and need to be further improved. In order to enlarge the scope of further applications, the development of future magnesium implants must aim at freedom of design and reduction of volume, hereby enabling higher functionalised implants, as e.g. plate systems or scaffold grafts for bone replacement therapy. In order to overcome the boundaries of conventional manufacturing methods such as turning or milling, the process of Laser Powder Bed Fusion (LPBF) for magnesium alloys was recently introduced. It enables the production of lattice structures, therefore allowing for reduction of implant material volume. Nevertheless, the concomitant increase of free surface of such magnesium scaffolds further stresses the aforementioned disadvantages of vast degradation and early loss of mechanical stability if not prevented by suitable postprocessing methods. Magnesium scaffold structures with different pore sizes were therefore manufactured by LPBF and consequently further modified either by thermal heat treatment or Plasma Electrolytic Oxidation (PEO). Implant performance was assessed by conducting degradation studies and mechanical testing. PEO modified scaffolds with small pore sizes exhibited improved long-term stability, while heat treated specimens showed impaired performance regarding degradation and mechanical stability. STATEMENT OF SIGNIFICANCE: Magnesium based scaffold structures offer wide possibilities for advanced functionalized bioabsorbable implants. By implementing lattice structures, big implant sizes and mechanically optimized implant geometries can be achieved enabling full bone replacement or large-scale plate systems, e.g. for orthopedic applications. As shape optimization and lattice structuring of such scaffolds consequently lead to enlarged surface, suitable design and postprocessing routines come into focus. The presented study addresses these new and relevant topics for the first time by evaluating geometry as well as heat and surface treatment options as input parameters for improved chemical and mechanical stability. The outcome of these variations is measured by degradation tests and mechanical analysis. Evaluating these methods, a significant contribution to the development of absorbable magnesium scaffolds is made. The findings can help to better understand the interdependence of high surface to volume ratio Magnesium implants and to deliver methods to incorporate such lattice structures into future large-scale implant applications manufactured from bioabsorbable Magnesium alloys.