In Vivo Evaluation of Mg-5%Zn-2%Nd Alloy as an Innovative Biodegradable Implant Material.

Mg-based alloys have been considered as potential structural materials for biodegradable implants in orthopedic and cardiovascular applications, particularly when combined with other biocompatible alloying elements. However, the performances of Mg-based alloys in in vitro conditions do not accurately reflect their behavior in an in vivo environment. As such, the present study aimed at evaluating the in vivo behavior of a novel Mg-5Zn-2Nd-0.13Y-0.35Zr alloy designated as ZE52 alloy. In vivo assessment was carried out using cylindrical disks implanted into the sub-cutaneous layer of the skin at the back midline of male Wistar rats for up to 11 weeks. Post-implantation responses evaluated included well-being behavior, blood biochemical tests and histology. The corrosion rate of the implants, expressed in terms of hydrogen gas formation, was evaluated by radiographic assessment and CT examination. Results of the well-being behavioral and blood biochemical tests indicated that the in vivo behavior of ZE52 alloy implants was similar to that of inert Ti-6Al-4V alloy implants introduced into a control group. Moreover, histological analysis did not reveal any severe inflammation, as compared to the reference alloy. However, significant sub-cutaneous gas cavities were observed, indicative of the accelerated degradation of the ZE52 alloy implants. The accelerated degradation was also manifested by the formation of alloy debris that was encapsulated within the gas cavities. Post-implantation gas bubble puncturing resulted in the complete degradation of the Mg-based implants, indicating that the inert nature of the gas prevented accelerated degradation of the alloy before it was naturally absorbed by the body.

Correction to: In Vivo Evaluation of Mg-5%Zn-2%Nd Alloy as an Innovative Biodegradable Implant Material.

The article In Vivo Evaluation of Mg-5%Zn-2%Nd Alloy as an Innovative Biodegradable Implant Materialwritten by Elkaiam et al. was originally published electronically on the publisher's internet portal (currently SpringerLink) on September 17, 2019 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on October 3, 2019 to Biomedical Engineering Society 2019 and the article is forthwith distributed under the terms of copyright.

Porous biodegradable EW62 medical implants resist tumor cell growth.

Magnesium alloys have been widely investigated for biodegradable medical applications. However, the shielding of harmful cells (eg. bacteria or tumorous cells) from immune surveillance may be compounded by the increased porosity of biodegradable materials. We previously demonstrated the improved corrosion resistance and mechanical properties of a novel EW62 (Mg-6%Nd-2%Y-0.5%Zr)) magnesium alloy by rapid solidification followed by extrusion (RS) compared to its conventional counterpart (CC). The present in vitro study evaluated the influence of rapid solidification on cytotoxicity to murine osteosarcoma cells. We found that CC and RS corrosion extracts significantly reduced cell viability over a 24-h exposure period. Cell density was reduced over 48 h following direct contact on both CC and RS surfaces, but was further reduced on the CC surface. The direct presence of cells accelerated corrosion for both materials. The corroded RS material exhibited superior mechanical properties relative to the CC material. The data show that the improved corrosion resistance of the rapidly solidified EW62 alloy (RS) resulted in a relatively reduced cytotoxic effect on tumorous cells. Hence, the tested alloy in the form of a rapidly solidified substance may introduce a good balance between its biodegradation characteristics and cytotoxic effect towards cancerous and normal cells.

The response of tenocytes to commercial scaffolds used for rotator cuff repair.

Surgical repairs of rotator cuff tears have high re-tear rates and many scaffolds have been developed to augment the repair. Understanding the interaction between patients' cells and scaffolds is important for improving scaffold performance and tendon healing. In this in vitro study, we investigated the response of patient-derived tenocytes to eight different scaffolds. Tested scaffolds included X-Repair, Poly-Tape, LARS Ligament, BioFiber (synthetic scaffolds), BioFiber-CM (biosynthetic scaffold), GraftJacket, Permacol, and Conexa (biological scaffolds). Cell attachment, proliferation, gene expression, and morphology were assessed. After one day, more cells attached to synthetic scaffolds with dense, fine and aligned fibres (X-Repair and Poly-Tape). Despite low initial cell attachment, the human dermal scaffold (GraftJacket) promoted the greatest proliferation of cells over 13 days. Expression of collagen types I and III were upregulated in cells grown on non-cross-linked porcine dermis (Conexa). Interestingly, the ratio of collagen I to collagen III mRNA was lower on all dermal scaffolds compared to synthetic and biosynthetic scaffolds. These findings demonstrate significant differences in the response of patient-derived tendon cells to scaffolds that are routinely used for rotator cuff surgery. Synthetic scaffolds promoted increased cell adhesion and a tendon-like cellular phenotype, while biological scaffolds promoted cell proliferation and expression of collagen genes. However, no single scaffold was superior. Our results may help understand the way that patients' cells interact with scaffolds and guide the development of new scaffolds in the future.

A layered electrospun and woven surgical scaffold to enhance endogenous tendon repair.

Surgical reattachments of tendon to bone in the rotator cuff are reported to fail in around 40% of cases. There are no adequate solutions to improve tendon healing currently available. Electrospun, sub-micron materials, have been extensively studied as scaffolds for tendon repair with promising results, but are too weak to be surgically implanted or to mechanically support the healing tendon. To address this, we developed a bonding technique that enables the processing of electrospun sheets into multi-layered, robust, implantable fabrics. Here, we show a first prototype scaffold created with this method, where an electrospun sheet was reinforced with a woven layer. The resulting scaffold presents a maximum suture pull out strength of 167N, closely matched with human rotator cuff tendons, and the desired nanofibre-mediated bioactivity in vitro and in vivo. This type of scaffold has potential for broader application for augmenting other soft tissues.

Improved stress corrosion cracking resistance of a novel biodegradable EW62 magnesium alloy by rapid solidification, in simulated electrolytes.

The high corrosion rate of magnesium (Mg) and Mg-alloys precludes their widespread acceptance as implantable biomaterials. Here, we investigated the potential for rapid solidification (RS) to increase the stress corrosion cracking (SCC) resistance of a novel Mg alloy, Mg-6%Nd-2%Y-0.5%Zr (EW62), in comparison to its conventionally cast (CC) counterpart. RS ribbons were extrusion consolidated in order to generate bioimplant-relevant geometries for testing and practical use. Microstructural characteristics were examined by SEM. Corrosion rates were calculated based upon hydrogen evolution during immersion testing. The surface layer of the tested alloys was analyzed by X-ray photoelectron spectroscopy (XPS). Stress corrosion resistance was assessed by slow strain rate testing and fractography. The results indicate that the corrosion resistance of the RS alloy is significantly improved relative to the CC alloy due to a supersaturated Nd enrichment that increases the Nd2O3 content in the external oxide layer, as well as a more homogeneous structure and reduced grain size. These improvements contributed to the reduced formation of hydrogen gas and hydrogen embrittlement, which reduced the SCC sensitivity relative to the CC alloy. Therefore, EW62 in the form of a rapidly solidified extruded structure may serve as a biodegradable implant for biomedical applications.

An electrospun polydioxanone patch for the localisation of biological therapies during tendon repair.

Rotator cuff tendon pathology is thought to account for 30-70 % of all shoulder pain. For cases that have failed conservative treatment, surgical re-attachment of the tendon to the bone with a non-absorbable suture is a common option. However, the failure rate of these repairs is high, estimated at up to 75 %. Studies have shown that in late disease stages the tendon itself is extremely degenerate, with reduced cell numbers and poor matrix organisation. Thus, it has been suggested that adding biological factors such as platelet rich plasma (PRP) and mesenchymal stem cells could improve healing. However, the articular capsule of the glenohumeral joint and the subacromial bursa are large spaces, and injecting beneficial factors into these sites does not ensure localisation to the area of tendon damage. Thus, the aim of this study was to develop a biocompatible patch for improving the healing rates of rotator cuff repairs. The patch will create a confinement around the repair area and will be used to guide injections to the vicinity of the surgical repair. Here, we characterised and tested a preliminary prototype of the patch utilising in vitro tools and primary tendon-derived cells, showing exceptional biocompatibility despite rapid degradation, improved cell attachment and that cells could migrate across the patch towards a chemo-attractant. Finally, we showed the feasibility of detecting the patch using ultrasound and injecting liquid into the confinement ex vivo. There is a potential for using this scaffold in the surgical repair of interfaces such as the tendon insertion in the rotator cuff, in conjunction with beneficial factors.

Tenocyte proliferation on collagen scaffolds protects against degradation and improves scaffold properties.

Tissue engineering scaffolds encourage cell proliferation whilst degrading to facilitate tissue regeneration. Their mechanical properties therefore change, decreasing due to scaffold degradation and increasing due to extracellular matrix deposition. This work compares the changing properties of collagen scaffolds incubated in culture medium, with and without human tenocytes, in order to investigate the relationship between degradation and tenocyte proliferation. The material properties of scaffolds are compared over 26 days using mechanical testing, differential scanning calorimetry, infra-red spectroscopy, and histology and biochemical assays. For medium-only scaffolds, the mechanical properties decrease rapidly, while culture medium sulfhydryl content increases significantly, with no significant changes in the denaturation temperature of scaffold collagen content. Conversely, the mechanical properties and collagen content of tenocyte-seeded scaffolds increase significantly while culture medium sulfhydryl content decreases and denaturation temperature remains the same. These results indicate that tenocytes proliferation both reduces the degradation of collagen scaffolds incubated in culture medium and produces scaffolds with improved properties.