PDLLA scaffolds with Cu‐ and Zn‐doped bioactive glasses having multifunctional properties for bone regeneration

Electrospun scaffolds are emerging as extracellular matrix (ECM)mimicking structures for tissue engineering thanks to their nanofibrous architecture. For the development of suitable electrospun scaffolds for bone tissue engineering, the addition of inorganic components has been implemented with the aim to confer important bioactivity like osteoinduction, osteointegration, and cell adhesion to the scaffolds. In this context, we propose a tricomponent electrospun scaffold composed of poly(d,l‐lactide), gelatin and RKKP glass‐ceramics. The bioactive RKKP glass‐ceramic system has attracted interest, due to the presence of ions such as La3+ and Ta5+, which turned out to be valuable as growth supporting agents for bones. In this work, RKKP glass‐ceramics were embedded inside the microfibers of electrospun scaffolds and the structural and biological properties were investigated. Our results showed that the glass‐ceramic microparticles were uniformly distributed in the fibrous structure of the scaffold. Furthermore, the glass‐ceramics promoted biomineralization of the scaffolds and improved cell viability and osteogenic differentiation. The mineralized layer formed on RKKP‐containing scaffolds after incubation in simulated body fluid medium has been shown to be hydroxyapatite by Raman spectroscopy and X‐ray diffraction. The results on differentiation studies of canine adipose‐derived mesenchymal stem cells grown on the electrospun scaffolds suggest that on varying the content of RKKP in the scaffold, it is possible to drive the differentiation toward chondrogenic or osteogenic commitment. The presence of ions, like La3+ and Ta5+, in the RKKP embedded polymeric composite scaffolds could play a role in supporting cell growth and promoting differentiation.

Section: Introductionmentioning

confidence: 99%

Electrospun poly(d,l‐lactide)/gelatin/glass‐ceramics tricomponent nanofibrous scaffold for bone tissue engineering

Bochicchio

Barbaro

Bonis

et al. 2020

“…Cu can act as an angiogenic agent and enhances in vivo angiogenesis and stimulates the proliferation of endothelial cell (Hu, 1998;Lakhkar et al, 2013). Zn and Cu incorporation into hybrid material has remarkable multifunctional properties in tissue engineering (Bejarano, Detsch, Boccaccini, & Palza, 2017). Zn and Cu incorporation into hybrid material has remarkable multifunctional properties in tissue engineering (Bejarano, Detsch, Boccaccini, & Palza, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…These biomaterials will also exert their antimicrobial effects to avoid the hazard of bacterial infections and reduce costs of treatment (Campoccia, Montanaro, & Arciola, 2013). So, it seems to be a logic approach to synthesize novel multipurpose scaffolds for regenerating the bones by designing multicomponent systems based on biodegradable polymers mixed with bioactive particles releasing ions, mainly, Cu +2 and Zn +2 (Bejarano et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Either Zn or Cu or both can be decorated into different types of materials such as polymers and ceramics with antibacterial and angiogenic properties and play an important role in deposition of collagen, cellular activity, and proliferation of osteoblasts (Balasubramanian, Strobel, Kneser, & Boccaccini, 2015;Erol et al, 2012). Zn and Cu incorporation into hybrid material has remarkable multifunctional properties in tissue engineering (Bejarano, Detsch, Boccaccini, & Palza, 2017). Therefore, we believed that coating of Zn-Cu imidazole MOF on a scaffold could improve the surface and biochemical properties of PLLA nanofiber scaffolds for tissue engineering purposes by promoting the bone cell attachment, proliferation, differentiation, and expression of osteogenic proteins (Dhand et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced osteogenic differentiation of mesenchymal stem cells on metal–organic framework based on copper, zinc, and imidazole coated poly‐l‐lactic acid nanofiber scaffolds

Telgerd

Sadeghinia

Birhanu

et al. 2019

The presence of inorganic bioactive minerals with polymers can accelerate and promote several processes including: bone cell joining, proliferation, differentiation, and expression of osteogenic proteins. In this study, zinc (Zn), copper (Cu), and imidazole metal–organic framework (MOF) nanoparticles were synthesized and coated over poly‐l‐lactic acid (PLLA) nanofibrous scaffolds for bone tissue engineering application. The surface and bioactive features of the scaffolds were characterized. The osteogenic potential of the scaffolds on human adipose tissue‐derived mesenchymal stem cells (MSCs) was evaluated. Zn–Cu imidazole MOF coated PLLA scaffolds (PLLA@MOF) showed a comparable rate of MSC proliferation with the pure PLLA scaffolds and tissue culture plate (TCP). However, the PLLA@MOF potential of osteogenic differentiation was significantly greater than either pristine PLLA scaffolds or TCP. Hence, coating Zn–Cu imidazole MOF has a significant effect on the osteogenesis of MSC. Therefore, PLLA@MOF is novel scaffolds with bioactive components which are crucial for osteoconductivity and also able to provoke the osteogenesis and angiogenesis.

“…Doping bioactive glasses with functional ions is important to modify their properties and enhance their interaction with the human body. Nevertheless, in most cases the doping ions were added separately, and their investigated effects were not compared to a parent glass (Bejarano, Detsch, Boccaccini, & Palza, 2017;Tylkowski & Brauer, 2013;Wers, Oudadesse, Lefeuvre, Bureau, & Merdrignac-Conanec, 2014). There have been a few systematic studies of combined doping with multiple elements, such as binary Sr 2+ -Li + dopants (Khan et al, 2016), but no such binary studies have been made on solgel derived bioglass.…”

mentioning

confidence: 99%

Cytotoxicity and bioactivity assessments for Cu²⁺ and La³⁺ doped high‐silica sol‐gel derived bioglasses: The complex interplay between additive ions revealed

Ben–Arfa

Palamà

Salvado

et al. 2019

We show the influence of two functional ions (Cu2+ and La3+), incorporated into a quaternary (Si, Ca, Na, P) sol‐gel derived bioactive glass system, on its particle size, cytotoxicity, and bioactivity. By doping the parent glass with the two ions in singular or combined forms, 15 doped glasses were prepared by a rapid sol‐gel technique. The influence of the combined doping on the particle size and cell viability was successfully evaluated by the aid of signal‐to‐noise‐ratio (S/N), using Taguchi analysis. This allowed us to analyze the complex interplay of effects between these ions, and the marked differences in biocompatibility between the three cell types studied. Cu addition had a significant effect on reducing the glass particle size, while both increased density. Cell viability was significantly improved for some doping combinations, demonstrating that while combined Cu–La doping was beneficial for biocompatibility with lymphoblasts, individual high‐Cu or low‐La doping was better with fibroblasts, and either high‐Cu or low‐La doping, or certain combined Cu–La combinations, were the optimum for osteoblasts. However, the bioactivity of doped samples was generally similar to that of the parent glass, although both La, and particularly Cu, did appear to aid dissolution of ions when immersed in SBF, act as glass modifiers, and encourage HAp crystallization. The results reveal that potential synergistic benefits can be obtained by combining the effects on the mean particle size, density, cytotoxicity, and bioactivity of the glasses. The greatly improved biocompatibility of some of the doped glasses makes them promising candidates for biomedical applications.