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  1. Md Yusop AH, Al Sakkaf A, Nur H
    J Biomed Mater Res B Appl Biomater, 2022 01;110(1):18-44.
    PMID: 34132457 DOI: 10.1002/jbm.b.34893
    Iron (Fe) and Fe-based scaffolds have become a research frontier in absorbable materials which is inherent to their promising mechanical properties including fatigue strength and ductility. Nevertheless, their slow corrosion rate and low biocompatibility have been their major obstacles to be applied in clinical applications. Over the last decade, various modifications on porous Fe-based scaffolds have been performed to ameliorate both properties encompassing surface coating, microstructural alteration via alloying, and advanced topologically order structural design produced by additive manufacturing (AM) techniques. The recent advent of AM produces topologically ordered porous Fe-based structures with an optimized architecture having controllable pore size and strut thickness, intricate internal design, and larger exposed surface area. This undoubtedly opens up new options for controlling Fe corrosion and its structural strengths. However, the in vitro biocompatibility of the AM porous Fe still needs to be addressed considering its higher corrosion rate due to the larger exposed surface area. This review summarizes the latest progress of the modifications on porous Fe-based scaffolds with a specific focus on their responses on the corrosion behavior and biocompatibility.
  2. Ulum MF, Arafat A, Noviana D, Yusop AH, Nasution AK, Abdul Kadir MR, et al.
    Mater Sci Eng C Mater Biol Appl, 2014 Mar 1;36:336-44.
    PMID: 24433920 DOI: 10.1016/j.msec.2013.12.022
    Biodegradable metals such as magnesium, iron and their alloys have been known as potential materials for temporary medical implants. However, most of the studies on biodegradable metals have been focusing on optimizing their mechanical properties and degradation behavior with no emphasis on improving their bioactivity behavior. We therefore investigated the possibility of improving iron biodegradation rate and bioactivity by incorporating various bioactive bioceramics. The iron-based bioceramic (hydroxyapatite, tricalcium phosphate and biphasic calcium phosphate) composites were prepared by mechanical mixing and sintering process. Degradation studies indicated that the addition of bioceramics lowered the corrosion potential of the composites and slightly increased their corrosion rate compared to that of pure iron. In vitro cytotoxicity results showed an increase of cellular activity when rat smooth muscle cells interacted with the degrading composites compared to pure iron. X-ray radiogram analysis showed a consistent degradation progress with that found in vivo and positive tissue response up to 70 days implantation in sheep animal model. Therefore, the iron-based bioceramic composites have the potential to be used for biodegradable bone implant applications.
  3. Yusop AH, Bakir AA, Shaharom NA, Abdul Kadir MR, Hermawan H
    Int J Biomater, 2012;2012:641430.
    PMID: 22919393 DOI: 10.1155/2012/641430
    Scaffolds have been utilized in tissue regeneration to facilitate the formation and maturation of new tissues or organs where a balance between temporary mechanical support and mass transport (degradation and cell growth) is ideally achieved. Polymers have been widely chosen as tissue scaffolding material having a good combination of biodegradability, biocompatibility, and porous structure. Metals that can degrade in physiological environment, namely, biodegradable metals, are proposed as potential materials for hard tissue scaffolding where biodegradable polymers are often considered as having poor mechanical properties. Biodegradable metal scaffolds have showed interesting mechanical property that was close to that of human bone with tailored degradation behaviour. The current promising fabrication technique for making scaffolds, such as computation-aided solid free-form method, can be easily applied to metals. With further optimization in topologically ordered porosity design exploiting material property and fabrication technique, porous biodegradable metals could be the potential materials for making hard tissue scaffolds.
  4. Md Yusop AH, Ulum MF, Al Sakkaf A, Hartanto D, Nur H
    Biotechnol J, 2021 Dec;16(12):e2100255.
    PMID: 34520117 DOI: 10.1002/biot.202100255
    Iron (Fe) and Fe-based materials have been vigorously explored in orthopedic applications in the past decade mainly owing to their promising mechanical properties including high yield strength, elastic modulus and ductility. Nevertheless, their corrosion products and low corrosion kinetics are the major concerns that need to be improved further despite their appealing mechanical strengths. The current studies on porous Fe-based scaffolds show an improved corrosion rate but the in vitro biocompatibility is still problematic in general. Unlike the Mg implants, the biodegradation and bioabsorption of Fe-based implants are still not well described. This vague issue could implicate the development of Fe-based materials as potential medical implants as they have not reached the clinical trial stage yet. Thus, there is a need to understand in-depth the Fe corrosion behavior and its bioabsorption mechanism to facilitate the material design of Fe-based scaffolds and further improve its biocompatibility. This manuscript provides an important insight into the basic bioabsorption of the multi-ranged Fe-based corrosion products with a review of the latest progress on the corrosion & in vitro biocompatibility of porous Fe-based scaffolds together with the remaining challenges and the perspective on the future direction.
  5. Md Yusop AH, Alsakkaf A, Noordin MA, Idris H, Nur H, Szali Januddi F
    J Biomed Mater Res B Appl Biomater, 2021 12;109(12):2184-2198.
    PMID: 33983686 DOI: 10.1002/jbm.b.34866
    This work is dedicated to the investigation of drug-release control by a direct effect of degradation from biodegradable metallic surfaces. Degradation behaviors characterized by surface morphology, immersion, and electrochemical techniques demonstrated that curcumin-coated zinc (c-Zn) had a higher degradation rate compared to curcumin-coated Fe (c-Fe). High anodic dissolution rate due to the higher degradation rate and widely extended groove-like degradation structure of c-Zn propelled a higher curcumin release. On the other hand, a slower curcumin release rate shown by c-Fe scaffolds is ascribed to its lower anodic dissolution and to its pitting degradation regime with relatively smaller pits. These findings illuminate the remarkable advantage of different degradation behaviors of degradable metallic surfaces in directly controlling the drug release without the need for external electrical stimulus.
  6. Yusop AH, Daud NM, Nur H, Kadir MR, Hermawan H
    Sci Rep, 2015;5:11194.
    PMID: 26057073 DOI: 10.1038/srep11194
    Iron and its alloy have been proposed as biodegradable metals for temporary medical implants. However, the formation of iron oxide and iron phosphate on their surface slows down their degradation kinetics in both in vitro and in vivo scenarios. This work presents new approach to tailor degradation behavior of iron by incorporating biodegradable polymers into the metal. Porous pure iron (PPI) was vacuum infiltrated by poly(lactic-co-glycolic acid) (PLGA) to form fully dense PLGA-infiltrated porous iron (PIPI) and dip coated into the PLGA to form partially dense PLGA-coated porous iron (PCPI). Results showed that compressive strength and toughness of the PIPI and PCPI were higher compared to PPI. A strong interfacial interaction was developed between the PLGA layer and the iron surface. Degradation rate of PIPI and PCPI was higher than that of PPI due to the effect of PLGA hydrolysis. The fast degradation of PIPI did not affect the viability of human fibroblast cells. Finally, this work discusses a degradation mechanism for PIPI and the effect of PLGA incorporation in accelerating the degradation of iron.
  7. Ulum MF, Nasution AK, Yusop AH, Arafat A, Kadir MR, Juniantito V, et al.
    J Biomed Mater Res B Appl Biomater, 2015 Oct;103(7):1354-65.
    PMID: 25385691 DOI: 10.1002/jbm.b.33315
    Iron-bioceramic composites have been developed as biodegradable implant materials with tailored degradation behavior and bioactive features. In the current work, in vivo bioactivity of the composites was comprehensively studied by using sheep animal model. Five groups of specimens (Fe-HA, Fe-TCP, Fe-BCP composites, and pure-Fe and SS316L as controls) were surgically implanted into medio proximal region of the radial bones. Real-time ultrasound analysis showed a decreased echo pattern at the peri-implant biodegradation site of the composites indicating minimal tissue response during the wound healing process. Peripheral whole blood biomarkers monitoring showed a normal dynamic change of blood cellular responses and no stress effect was observed. Meanwhile, the released Fe ion concentration was increasing along the implantation period. Histological analysis showed that the composites corresponded with a lower inflammatory giant cell count than that of SS316L. Analysis of the retrieved implants showed a thicker degradation layer on the composites compared with pure-Fe. It can be concluded that the iron-bioceramic composites are bioactive and induce a preferable wound healing process.
  8. Md Yusop AH, Wan Ali WFF, Jamaludin FH, Szali Januddi F, Sarian MN, Saad N, et al.
    Biotechnol J, 2024 Mar;19(3):e2300464.
    PMID: 38509814 DOI: 10.1002/biot.202300464
    The present study evaluates the corrosion behavior of poly[xylitol-(1,12-dodecanedioate)](PXDD)-HA coated porous iron (PXDD140/HA-Fe) and its cell-material interaction aimed for temporary bone scaffold applications. The physicochemical analyses show that the addition of 20 wt.% HA into the PXDD polymers leads to a higher crystallinity and lower surface roughness. The corrosion assessments of the PXDD140/HA-Fe evaluated by electrochemical methods and surface chemistry analysis indicate that HA decelerates Fe corrosion due to a lower hydrolysis rate following lower PXDD content and being more crystalline. The cell viability and cell death mode evaluations of the PXDD140/HA-Fe exhibit favorable biocompatibility as compared to bare Fe and PXDD-Fe scaffolds owing to HA's bioactive properties. Thus, the PXDD140/HA-Fe scaffolds possess the potential to be used as a biodegradable bone implant.
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