Polylactic acid-based porous scaffolds doped with calcium silicate and dicalcium phosphate dihydrate designed for biomedical application

Gandolfi, Maria Giovanna; Zamparini, Fausto; Esposti, Mauro Degli; Chiellini, Emo; Aparicio, Conrado; Fava, Fabio; Fabbri, Paola; Taddei, Paola; Prati, Carlo

doi:10.1016/j.msec.2017.08.040

Cited by 64 publications

(78 citation statements)

References 90 publications

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“…For example, Tetsushi Taguchi et al had fabricated the reactive poly(vinyl alcohol) (PVA) membrane for the prevention of bone cement leakage with good potential for implantable balloon kyphoplasty, but further investigations on its clinical efficiency are still in progress [12].On the other hand, polymeric membranes fabricated from a single material more often have limited biological performance compared to the use of hybrid biomaterials composed of biodegradable synthetic polymers and inorganic materials, with the hybrid biomaterials fitting better to bone tissue engineering applications due to their similar compositions to natural bones [13,14]. For example, biodegradable polymers such as poly(L-lactic acid) (PLLA) (L-lactic acid isomer of polylactic acid (PLA), an aliphatic thermoplastic polyester obtained by polymerizing lactide monomers) have been used for scaffold design doped with dicalcium silicate (C 2 S) nanoparticles as an ideal candidate for novel bone graft substitutes with enhanced mechanical and biodegradable properties, and biointeractive nature [15,16]. Scaffolds fabricated from (PLLA)/dicalcium phosphate dihydrate (DCPD) composite by indirect casting had also shown to effectively improve the mechanical strength and biocompatibility for the repair of bone defects when compared to the scaffold from neat PLLA [17].…”

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confidence: 99%

Fabrication of PLLA/C3S Composite Membrane for the Prevention of Bone Cement Leakage

et al. 2019

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Kyphoplasty is an important treatment for stabilizing spine fractures due to osteoporosis. However, leakage of polymethyl-methacrylate (PMMA) bone cement during this procedure into the spinal canal has been reported to cause many adverse effects. In this study, we prepared an implantable membrane to serve as a barrier that avoids PMMA cement leakage during kyphoplasty procedures through a hybrid composite made of poly-l-lactic acid (PLLA) and tricalcium silicate (C 3 S), with the addition of C 3 S into PLLA matrix, showing enhanced mechanical and anti-degradation properties while keeping good cytocompatibility when compared to PLLA alone and most importantly, when this material design was applied under standardized PMMA cement injection conditions, no posterior wall leakage was observed after the kyphoplasty procedure in pig lumbar vertebral bone models. Testing results assess its effectiveness for clinical practice.2 of 17 the created cavity after balloon inflation during the kyphoplasty procedure [10]. Following which the balloon is re-inserted and inflated, creating a cement shell or a cement membrane around the inner walls of the created cavity, and another batch of cement was mixed and injected into the remaining cavity thereafter with limited cement leakage possibility from initial cement setting. Although this double cement application with PMMA as the cement anti-leakage shell or membrane has demonstrated its efficacy in clinical trial during the kyphoplasty procedure [11], the long term complications might be devastating due to PMMA presence on the bone cement surface [9], which makes the development of a new material design for anti-leakage membrane necessary. For example, Tetsushi Taguchi et al. had fabricated the reactive poly(vinyl alcohol) (PVA) membrane for the prevention of bone cement leakage with good potential for implantable balloon kyphoplasty, but further investigations on its clinical efficiency are still in progress [12].On the other hand, polymeric membranes fabricated from a single material more often have limited biological performance compared to the use of hybrid biomaterials composed of biodegradable synthetic polymers and inorganic materials, with the hybrid biomaterials fitting better to bone tissue engineering applications due to their similar compositions to natural bones [13,14]. For example, biodegradable polymers such as poly(L-lactic acid) (PLLA) (L-lactic acid isomer of polylactic acid (PLA), an aliphatic thermoplastic polyester obtained by polymerizing lactide monomers) have been used for scaffold design doped with dicalcium silicate (C 2 S) nanoparticles as an ideal candidate for novel bone graft substitutes with enhanced mechanical and biodegradable properties, and biointeractive nature [15,16]. Scaffolds fabricated from (PLLA)/dicalcium phosphate dihydrate (DCPD) composite by indirect casting had also shown to effectively improve the mechanical strength and biocompatibility for the repair of bone defects when compared to the scaffold from neat PLLA [17]. From which the h...

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confidence: 99%

Fabrication of PLLA/C3S Composite Membrane for the Prevention of Bone Cement Leakage

et al. 2019

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“…The scaffolds were prepared through TIPS according to a previous protocol [28][29][30]. PLA or PCL solutions in 1,4-dioxane were obtained, reaching a 3.5% wt/vol concentration.…”

Section: Scaffolds Preparationmentioning

confidence: 99%

“…CaSi and DCPD mineral powders were added in 10% by weight with respect to PCL or PLA. The solutions were sonicated for 3 h using a ultrasonic processor UP50H (Hielsher, Teltow, Germany; operative parameters 50 W, 30 kHz) with a 2 mm sonotrode MSD titanium tip, then put inside 60 mm plates and cooled at −18 • C for 18 h. Finally, the frozen samples were extracted and immersed in an ethanol bath (Sigma-Aldrich, Milan, Italy) precooled at −18 • C for 18 h, with a solvent refresh every 3 h [29,30].…”

Section: Scaffolds Preparationmentioning

confidence: 99%

“…The images were analyzed using Image J program (National Institutes of Health, Bethesda, MY, USA) to evaluate the surface porosity of the scaffolds, calculated as the ratio between the blackest areas (corresponding to the micropores) and the total investigated area [29,32].…”

Section: Surface Porosity Evaluated By the Morphometric Analysis On Ementioning

confidence: 99%

“…have been designed for angiogenic and osteogenic purposes containing bioactive calcium silicates [31]. Recently, highly porous PLA and PCL scaffolds doped with bioactive calcium silicates and calcium phosphates have been designed [28][29][30]. Mineral-doped PLA scaffolds demonstrated the ability to be colonized by oral derived mesenchymal stem cells and to stimulate their shift through osteogenic lineage [28].…”

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Vascular Wall–Mesenchymal Stem Cells Differentiation on 3D Biodegradable Highly Porous CaSi-DCPD Doped Poly (α-hydroxy) Acids Scaffolds for Bone Regeneration

et al. 2020

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Vascularization is a crucial factor when approaching any engineered tissue. Vascular wall-mesenchymal stem cells are an excellent in vitro model to study vascular remodeling due to their strong angiogenic attitude. This study aimed to demonstrate the angiogenic potential of experimental highly porous scaffolds based on polylactic acid (PLA) or poly-e-caprolactone (PCL) doped with calcium silicates (CaSi) and dicalcium phosphate dihydrate (DCPD), namely PLA-10CaSi-10DCPD and PCL-10CaSi-10DCPD, designed for the regeneration of bone defects. Vascular wall-mesenchymal stem cells (VW-MSCs) derived from pig thoracic aorta were seeded on the scaffolds and the expression of angiogenic markers, i.e. CD90 (mesenchymal stem/stromal cell surface marker), pericyte genes α-SMA (alpha smooth muscle actin), PDGFR-β (platelet-derived growth factor receptor-β), and NG2 (neuron-glial antigen 2) was evaluated. Pure PLA and pure PCL scaffolds and cell culture plastic were used as controls (3D in vitro model vs. 2D in vitro model). The results clearly demonstrated that the vascular wall mesenchymal cells colonized the scaffolds and were metabolically active. Cells, grown in these 3D systems, showed the typical gene expression profile they have in control 2D culture, although with some main quantitative differences. DNA staining and immunofluorescence assay for alpha-tubulin confirmed a cellular presence on both scaffolds. However, VW-MSCs cultured on PLA-10CaSi-10DCPD showed an individual cells growth, whilst on PCL-10CaSi-10DCPD scaffolds VW-MSCs grew in spherical clusters. In conclusion, vascular wall mesenchymal stem cells demonstrated the ability to colonize PLA and PCL scaffolds doped with CaSi-DCPD for new vessels formation and a potential for tissue regeneration.

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Extrusion 3D‐printed tricalcium phosphate‐polycaprolactone biocomposites for quercetin‐KCl delivery in bone tissue engineering

Toulou,

Chaudhari,

Bose

2024

J Biomedical Materials Res

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Critical‐sized bone defects pose a significant challenge in advanced healthcare due to limited bone tissue regenerative capacity. The complex interplay of numerous overlapping variables hinders the development of multifunctional biocomposites. Phytochemicals show promise in promoting bone growth, but their dose‐dependent nature and physicochemical properties halt clinical use. To develop a comprehensive solution, a 3D‐printed (3DP) extrusion‐based tricalcium phosphate‐polycaprolactone (TCP‐PCL) scaffold is augmented with quercetin and potassium chloride (KCl). This composite material demonstrates a compressive strength of 30 MPa showing promising stability for low load‐bearing applications. Quercetin release from the scaffold follows a biphasic pattern that persists for up to 28 days, driven via diffusion‐mediated kinetics. The incorporation of KCl allows for tunable degradation rates of scaffolds and prevents the initial rapid release. Functionalization of scaffolds facilitates the attachment and proliferation of human fetal osteoblasts (hfOB), resulting in a 2.1‐fold increase in cell viability. Treated scaffolds exhibit a 3‐fold reduction in osteosarcoma (MG‐63) cell viability as compared to untreated substrates. Ruptured cell morphology and decreased mitochondrial membrane potential indicate the antitumorigenic potential. Scaffolds loaded with quercetin and quercetin‐KCl (Q‐KCl) demonstrate 76% and 89% reduction in bacterial colonies of Staphylococcus aureus, respectively. This study provides valuable insights as a promising strategy for bone tissue engineering (BTE) in orthopedic repair.

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Polylactic acid-based porous scaffolds doped with calcium silicate and dicalcium phosphate dihydrate designed for biomedical application

Cited by 64 publications

References 90 publications

Fabrication of PLLA/C3S Composite Membrane for the Prevention of Bone Cement Leakage

Fabrication of PLLA/C3S Composite Membrane for the Prevention of Bone Cement Leakage

Vascular Wall–Mesenchymal Stem Cells Differentiation on 3D Biodegradable Highly Porous CaSi-DCPD Doped Poly (α-hydroxy) Acids Scaffolds for Bone Regeneration

Extrusion 3D‐printed tricalcium phosphate‐polycaprolactone biocomposites for quercetin‐KCl delivery in bone tissue engineering

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