Localised controlled release of simvastatin from porous chitosan–gelatin scaffolds engrafted with simvastatin loaded PLGA-microparticles for bone tissue engineering application

Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Daly, Jacqueline S.; Chiono, Valeria; Mattu, Clara; Tonda‐Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

doi:10.1016/j.msec.2015.10.014

Cited by 94 publications

(53 citation statements)

References 39 publications

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“…Numerous studies have reported that the local delivery of simvastatin from carriers such as α-tricalcium phosphate and polylactic acid membranes lead to an increase in bone healing [49] [52]. In addition, a recent in vitro study by Gentile et al showed a controlled localized release of simvastatin over 11 days from porous chitosan-gelatin scaffolds was needed to influence the osteoblastic proliferation and differentiation [61]. In this study, while the histomorphometric data of the simvastatin loaded membranes group showed a better bone response than that of control membranes at 8 weeks, the effect of simvastatin in bone formation was modest and not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Bone Regeneration of Simvastatin Loaded Chitosan Nanofiber Membranes in Rodent Calvarial Defects

Ghadri¹,

Anderson²,

Adatrow³

et al. 2018

JBNB

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Chitosan nanofiber membranes have been known to have a high degree of biocompatibility and support new bone formation with controllable biodegradation. The surface area of these membranes may allow them to serve as local delivery carriers for different biologic mediators. Simvastatin, a drug commonly used for lowering cholesterol, has demonstrated promising bone regenerative capability. The aim of this study was to evaluate simvastatin loaded chitosan nanofiber membranes for guided bone regeneration (GBR) applications and their ability to enhance bone formation in rat calvarial defects. Nanofibrous chitosan membranes with random fiber orientation were fabricated by electrospinning technique and loaded with 0.25 mg of simvastatin under sterile conditions. One membrane was implanted subperiosteally to cover an 8 mm diameter critical size calvarial defect. Two groups: 1) Control: non-loaded chitosan membranes; 2) Experimental: chitosan membranes loaded with 0.25 mg of simvastatin were evaluated histologically and via micro-computed tomography (micro-CT) for bone formation at 4 and 8 weeks time points (n = 5/group per time point). Both groups exhibited good biocompatibility with only mild or moderate inflammatory response during the healing process. Histologic and micro-CT evaluations confirmed bone formation in calvarial defects as early as 4 weeks using control and experimental membranes. In addition, newly-formed bony bridges consolidating calvarial defects histologically along with partial radiographic defect coverage were observed at 8 weeks in both groups.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Bone Regeneration of Simvastatin Loaded Chitosan Nanofiber Membranes in Rodent Calvarial Defects

Ghadri¹,

Anderson²,

Adatrow³

et al. 2018

JBNB

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“…Osteochondral tissue is composed of two regions, superficial articular cartilage and underlying subchondral bone. Therefore, a biomimetic bilayered scaffold with two components is appropriate to guide the regeneration of the layer‐specific chondral and bone matrix . As the cartilage layer, collagen is flexible and can thus adapt to the joint curvature and contains specific molecular domains that induce and support cell bioactivity .…”

Section: Discussionmentioning

confidence: 99%

Calcium Phosphate–Collagen Scaffold with Aligned Pore Channels for Enhanced Osteochondral Regeneration

Seong

Kang

Song

et al. 2017

Adv Healthcare Materials

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This study reports the development of a bilayered scaffold with aligned channels produced via a sequential coextrusion and unidirectional freezing process to facilitate upward bone-marrow stem-cell migration. The biomimetic scaffold with collagen and biphasic calcium phosphate (BCP) layers is successfully fabricated with matching of the cartilage and bone layers. The aligned structure results in an enhancement of the compressive strength, and the channels enable tight anchoring of the collagen layers on the BCP scaffolds compared with a randomly structured porous scaffold. An in vitro evaluation demonstrates that the aligned channels guide the cells to attach on the surface in highly stretched shapes and migrate upward faster than the random structure. In addition, in vivo assessment reveals that the aligned channels yield superior osteochondral tissue regeneration compared with the random structure. Moreover, the channel diameter greatly affects the tissue regeneration, and the scaffold with a channel diameter of ≈270 µm exhibits the optimal regeneration because of sufficient nutrient supply and adequate tissue ingrowth. These findings indicate that the introduction of aligned channels to a bilayered scaffold provides an effective approach for osteochondral tissue regeneration.

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“…8, 11-13 At present, more and more researchers devote to endowing the natural polymers with more specific functionalities to tailor the biological, mechanical, degradation properties for special applications, such as modification with specific active groups, grafting polymers, and so on. [14][15][16][17] For bone tissue engineering, the biomaterials should be designed to have almost the same structure and properties with those of the natural bone tissues, especially for load-bearing bone tissues. Besides biocompatibility, the implants must have sufficient mechanical strength to support the human body.…”

Section: Introductionmentioning

confidence: 99%

Carboxylated Agarose (CA)-Silk Fibroin (SF) Dual Confluent Matrices Containing Oriented Hydroxyapatite (HA) Crystals: Biomimetic Organic/Inorganic Composites for Tibia Repair

Ran

Chen

et al. 2016

Biomacromolecules

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By in situ combining the dual cross-linking matrices of the carboxylated agarose (CA) and the silk fibroin (SF) with the hydroxyapatite (HA) crystals, the CA-SF/HA composites with optimal physicochemical and biological properties were obtained, which were designed to meet the clinical needs of load-bearing bone repair. With the synergistic modulation of the dual organic matrices, the HA nanoparticles presented sheet and rod morphologies due to the preferred orientation, which successfully simulated the biomineralization in nature. The chemical reactivity of the native agarose (NA) was significantly enhanced via carboxylation, and the CA exhibited higher thermal stability than the NA. In the presence of SF, the composites showed optimal mechanical properties that could meet the standard of bone repair. The degradation of the composites in the presence of CA and SF was significantly delayed such that the degradation rate of the implant could satisfy the growth rate of the newly formed bone tissue. The in vitro tests confirmed that the CA-SF/HA composite scaffolds enabled the MG63 cells to proliferate and differentiate well, and the CA/HA composite presented greater capability of promoting the cell behaviors than the NA/HA composite. After 24 days of implantation, newly formed bone was observed at the tibia defect site and around the implant. Extensive osteogenesis was presented in the rats treated with the CA-SF/HA composites. In general, the CA-SF/HA composites prepared in this work had the great potential to be applied for repairing large bone defects.

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Localised controlled release of simvastatin from porous chitosan–gelatin scaffolds engrafted with simvastatin loaded PLGA-microparticles for bone tissue engineering application

Cited by 94 publications

References 39 publications

Evaluation of Bone Regeneration of Simvastatin Loaded Chitosan Nanofiber Membranes in Rodent Calvarial Defects

Evaluation of Bone Regeneration of Simvastatin Loaded Chitosan Nanofiber Membranes in Rodent Calvarial Defects

Calcium Phosphate–Collagen Scaffold with Aligned Pore Channels for Enhanced Osteochondral Regeneration

Carboxylated Agarose (CA)-Silk Fibroin (SF) Dual Confluent Matrices Containing Oriented Hydroxyapatite (HA) Crystals: Biomimetic Organic/Inorganic Composites for Tibia Repair

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