Promotion of In Vitro Osteogenic Activity by Melt Extrusion-Based PLLA/PCL/PHBV Scaffolds Enriched with Nano-Hydroxyapatite and Strontium Substituted Nano-Hydroxyapatite

Kontogianni, Georgia-Ioanna; Bonatti, Amedeo Franco; Maria, Carmelo De; Naseem, Raasti; Melo, Priscila; Coelho, Catarina C.; Vozzi, Giovanni; Dalgarno, Kenneth; Quadros, Paulo A.; Vitale-Brovarone, C.; Chatzinikolaidou, Μaria

doi:10.3390/polym15041052

Cited by 20 publications

(18 citation statements)

References 71 publications

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“…Due to the wide range of processable materials, low material and use cost, environmental protection, and nontoxicity, fused deposition modeling (FDM), as the most common 3D printing technology, offers the potential for design and manufacturing in the combination of polymers and the biomedical field [ 32 , 33 ]. Furthermore, FDM has shown obvious competitiveness in the preparation of biodegradable polymer bone scaffolds including PLA [ 34 , 35 , 36 ]. However, to the best of our knowledge, there are few studies currently available on PLA/Mg(OH) 2 porous bone scaffolds, let alone those using FDM 3D printing technology.…”

Section: Introductionmentioning

confidence: 99%

Magnesium Hydroxide as a Versatile Nanofiller for 3D-Printed PLA Bone Scaffolds

Guo,

Bu,

Mao

et al. 2024

Polymers

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Polylactic acid (PLA) has attracted much attention in bone tissue engineering due to its good biocompatibility and processability, but it still faces problems such as a slow degradation rate, acidic degradation product, weak biomineralization ability, and poor cell response, which limits its wider application in developing bone scaffolds. In this study, Mg(OH)2 nanoparticles were employed as a versatile nanofiller for developing PLA/Mg(OH)2 composite bone scaffolds using fused deposition modeling (FDM) 3D printing technology, and its mechanical, degradation, and biological properties were evaluated. The mechanical tests revealed that a 5 wt% addition of Mg(OH)2 improved the tensile and compressive strengths of the PLA scaffold by 20.50% and 63.97%, respectively. The soaking experiment in phosphate buffered solution (PBS) revealed that the alkaline degradation products of Mg(OH)2 neutralized the acidic degradation products of PLA, thus accelerating the degradation of PLA. The weight loss rate of the PLA/20Mg(OH)2 scaffold (15.40%) was significantly higher than that of PLA (0.15%) on day 28. Meanwhile, the composite scaffolds showed long-term Mg2+ release for more than 28 days. The simulated body fluid (SBF) immersion experiment indicated that Mg(OH)2 promoted the deposition of apatite and improved the biomineralization of PLA scaffolds. The cell culture of bone marrow mesenchymal stem cells (BMSCs) indicated that adding 5 wt% Mg(OH)2 effectively improved cell responses, including adhesion, proliferation, and osteogenic differentiation, due to the release of Mg2+. This study suggests that Mg(OH)2 can simultaneously address various issues related to polymer scaffolds, including degradation, mechanical properties, and cell interaction, having promising applications in tissue engineering.

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Section: Introductionmentioning

confidence: 99%

Magnesium Hydroxide as a Versatile Nanofiller for 3D-Printed PLA Bone Scaffolds

Guo,

Bu,

Mao

et al. 2024

Polymers

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“…The past few decades have witnessed the rapid development of scaffolds for BTE, owing to the increasing abundance of biomaterials and continuous emergence of new fabrication techniques [10,12]. Different categories of biomaterials have been explored to construct BTE scaffolds for cranial bone regeneration including metals, ceramics, polymers, hydrogels, and composites, among which bioactive composites have demonstrated enhanced bone repairing capabilities as they combine the advantages of individual groups of materials, providing greater flexibility in tuning the biological, mechanical, and structural properties of the engineered scaffolds [13][14][15][16][17][18][19][20][21][22][23][24][25]. For example, Kim et al have developed a multifunctional hybrid scaffold by immobilizing a bioactive nanocomplex (NC) composed of bone morphogenetic protein 2 (BMP2) and polydeoxyribonucleotide (PDRN) on a preformed scaffold (PME) comprising poly(lactic-co-glycolic) acid (PLGA), ricinoleic acid modified magnesium hydroxide (mMH), and bone extracellular matrix (bECM) [17].…”

Section: Introductionmentioning

confidence: 99%

Towards the Clinical Translation of 3D PLGA/β-TCP/Mg Composite Scaffold for Cranial Bone Regeneration

Zhou,

Hu,

et al. 2024

Materials

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Recent years have witnessed the rapid development of 3D porous scaffolds with excellent biocompatibility, tunable porosity, and pore interconnectivity, sufficient mechanical strength, controlled biodegradability, and favorable osteogenesis for improved results in cranioplasty. However, clinical translation of these scaffolds has lagged far behind, mainly because of the absence of a series of biological evaluations. Herein, we designed and fabricated a composite 3D porous scaffold composed of poly (lactic-co-glycolic) acid (PLGA), β-tricalcium phosphate (β-TCP), and Mg using the low-temperature deposition manufacturing (LDM) technique. The LDM-engineered scaffolds possessed highly porous and interconnected microstructures with a porosity of 63%. Meanwhile, the scaffolds exhibited mechanical properties close to that of cancellous bone, as confirmed by the compression tests. It was also found that the original composition of scaffolds could be maintained throughout the fabrication process. Particularly, two important biologic evaluations designed for non-active medical devices, i.e., local effects after implantation and subchronic systemic toxicity tests, were conducted to evaluate the local and systemic toxicity of the scaffolds. Additionally, the scaffolds exhibited significant higher mRNA levels of osteogenic genes compared to control scaffolds, as confirmed by an in vitro osteogenic differentiation test of MC3T3-E1 cells. Finally, we demonstrated the improved cranial bone regeneration performance of the scaffolds in a rabbit model. We envision that our investigation could pave the way for translating the LDM-engineered composite scaffolds into clinical products for cranial bone regeneration.

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“…Specifically, nanoHA holds great promise for various applications, particularly in the treatment of bone defects such as those derived from osteoporotic pathologies, a significant global health concern characterized by brittle bones [ 8 ], leading to decreased bone mass, increased fracture risk, and reduced bone strength. In this context, bone fractures can be treated either by filling them with medical devices enriched with nanoHA, such as bioactive bone cements and osteogenic injectable hydrogels and microspheres [ 9 ] containing nanoHA, polymeric composite matrices such as 3D osteogenic scaffolds [ 10 ], or coatings of metallic implants with nanoHA compounds [ 11 , 12 ]. The use of minimally and noninvasive therapeutic agents for bone tumor ablation and bone regeneration as bifunctional materials is another recently reported challenge [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Osteogenic Potential of Nano-Hydroxyapatite and Strontium-Substituted Nano-Hydroxyapatite

Kontogianni

Coelho²,

Gauthier

et al. 2023

Nanomaterials

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Nanohydroxyapatite (nanoHA) is the major mineral component of bone. It is highly biocompatible, osteoconductive, and forms strong bonds with native bone, making it an excellent material for bone regeneration. However, enhanced mechanical properties and biological activity for nanoHA can be achieved through enrichment with strontium ions. Here, nanoHA and nanoHA with a substitution degree of 50 and 100% of calcium with strontium ions (Sr-nanoHA_50 and Sr-nanoHA_100, respectively) were produced via wet chemical precipitation using calcium, strontium, and phosphorous salts as starting materials. The materials were evaluated for their cytotoxicity and osteogenic potential in direct contact with MC3T3-E1 pre-osteoblastic cells. All three nanoHA-based materials were cytocompatible, featured needle-shaped nanocrystals, and had enhanced osteogenic activity in vitro. The Sr-nanoHA_100 indicated a significant increase in the alkaline phosphatase activity at day 14 compared to the control. All three compositions revealed significantly higher calcium and collagen production up to 21 days in culture compared to the control. Gene expression analysis exhibited, for all three nanoHA compositions, a significant upregulation of osteonectin and osteocalcin on day 14 and of osteopontin on day 7 compared to the control. The highest osteocalcin levels were found for both Sr-substituted compounds on day 14. These results demonstrate the great osteoinductive potential of the produced compounds, which can be exploited to treat bone disease.

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Promotion of In Vitro Osteogenic Activity by Melt Extrusion-Based PLLA/PCL/PHBV Scaffolds Enriched with Nano-Hydroxyapatite and Strontium Substituted Nano-Hydroxyapatite

Cited by 20 publications

References 71 publications

Magnesium Hydroxide as a Versatile Nanofiller for 3D-Printed PLA Bone Scaffolds

Magnesium Hydroxide as a Versatile Nanofiller for 3D-Printed PLA Bone Scaffolds

Towards the Clinical Translation of 3D PLGA/β-TCP/Mg Composite Scaffold for Cranial Bone Regeneration

Osteogenic Potential of Nano-Hydroxyapatite and Strontium-Substituted Nano-Hydroxyapatite

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