Delivery of Bioactive Lipids from Composite Microgel-Microsphere Injectable Scaffolds Enhances Stem Cell Recruitment and Skeletal Repair

Das, Ashim; Barker, Daniel A.; Wang, Tiffany; Lau, Cheryl M.; Lin, Yong; Botchwey, Edward A.

doi:10.1371/journal.pone.0101276

Cited by 28 publications

(26 citation statements)

References 58 publications

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“…Some studies have focused on the recruitment of MSCs to the bone defect site for treating the nonunions. Das et al [2014] showed that FTY720 (a small molecule) enhances MSC recruitment to the calvarial defect of rats, thus promoting skeletal repair. They suggested that sustained release of FTY720 from injected microspheres used alone or in combination with rhBMP-2 improves the recruitment of MSCs and subsequently increases bone repair.…”

Section: Msc Homing and Recruitment To Bone Defectsmentioning

confidence: 99%

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

285

204

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Healing and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts. The effectiveness of MSC therapy is dependent on several factors, including the differentiating state of the MSCs at the time of application, the method of their delivery, the concentration of MSCs per injection, the vehicle used, and the nature and extent of injury, for example. Tissue engineering and regenerative medicine, together with genetic engineering and gene therapy, are advanced options that may have the potential to improve the outcome of cell therapy. Although several in vitro and in vivo investigations have suggested the potential roles of MSCs in bone repair and regeneration, the mechanism of MSC therapy in bone repair has not been fully elucidated, the efficacy of MSC therapy has not been strongly proven in clinical trials, and several controversies exist, making it difficult to draw conclusions from the results. In this review, we update the recent advances in the mechanisms of MSC action and the delivery approaches in bone regenerative medicine. We will also review the most recent clinical trials to find out how MSCs may be beneficial for treating bone defects.

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Section: Msc Homing and Recruitment To Bone Defectsmentioning

confidence: 99%

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

285

204

View full text Add to dashboard Cite

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“…We have shown previously that local administration of FTY720 regulates the trafficking of inflammatory and osteogenic progenitor cells to sites of injury [9, 10, 32]. In order to assess the phenotype of cells recruited to the graft region, we performed immunohistochemical staining on defect tissue sections to visualize macrophages (CD68) and stromal populations enriched for osteogenic progenitor cells (CD29, CD90) [32].…”

Section: Resultsmentioning

confidence: 99%

“…In order to assess the phenotype of cells recruited to the graft region, we performed immunohistochemical staining on defect tissue sections to visualize macrophages (CD68) and stromal populations enriched for osteogenic progenitor cells (CD29, CD90) [32]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Enhanced osseous integration of human trabecular allografts following surface modification with bioactive lipids

Wang

Krieger

Huang

et al. 2015

Drug Deliv. and Transl. Res.

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In this study, we used extracellular matrix (ECM) gels and human bone allograft as matrix vehicles to deliver the sphingolipid growth factor FTY720 to rodent models of tibial fracture and a critical-sized cranial defect. We show that FTY720 released from injectable ECM gels may accelerate callous formation and resolution and bone volume in a mouse tibial fracture model. We then show that FTY720 binds directly to human trabecular allograft bone and releases over 1 week in vitro. Rat critical-sized cranial defects treated with FTY720-coated grafts show increases in vascularization and bone deposition, with histological and micro-computed topography (microCT) evidence of enhanced bone formation within the graft and defect void. Immunohistochemical analysis suggests that osteogenesis within FTY720-coated grafts is associated with reduced CD68+ macrophage infiltration and recruitment of CD29+ bone progenitor cells. Matrix binding of FTY720 thus represents a promising and robust bone regeneration strategy with potential clinical translatability.

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“…Because FTY720 affects both the recruitment and cytokine elaboration of MO [9], and because sustained release of FTY720 over several weeks can be achieved using PLGA microparticle carriers [17], we next attempted therapeutic immunomodulation using local delivery of FTY720-loaded PLGA microparticles (Figure 3a). To achieve sustained local delivery of FTY720 during the progression of immune cell infiltration, 50:50 PLGA microparticles encapsulating FTY720 (total dose encapsulated in microparticles = 10 μg, drug:polymer ratio = 1:150) were injected into supraspinatus muscle at the time of surgery.…”

Section: Resultsmentioning

confidence: 99%

Solar Energy Storage via Thermochemical Metal Oxide/Metal Sulfate Water Splitting Cycle

et al. 2018

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Full thickness rotator cuff tears (RCT) and the associated muscle degeneration that results due to this injury presents a significant clinical burden. The prevention or recovery from this degeneration requires the synchronized behavior of many cells that participate in regeneration. Strategies that tune the inflammatory cascade that is initiated after injury serves as a powerful way to influence tissue repair. Here, we use the local, sustained delivery of the immunomodulatory small molecule FTY720 to examine whether the recruitment of pro-regenerative myeloid cells affects the healing outcome. We find that PLGA microparticles have an atrophic effect on the muscle that is ameliorated with the release of FTY720. However, the inability of FTY720 delivery to induce pro-regenerative monocyte and macrophage recruitment and our findings demonstrating enrichment of CD4+ T cells suggest that effects of this small molecule are context dependent and that the underlying mechanisms behind this RCT associated muscle degeneration require further studies.

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Delivery of Bioactive Lipids from Composite Microgel-Microsphere Injectable Scaffolds Enhances Stem Cell Recruitment and Skeletal Repair

Cited by 28 publications

References 58 publications

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Enhanced osseous integration of human trabecular allografts following surface modification with bioactive lipids

Solar Energy Storage via Thermochemical Metal Oxide/Metal Sulfate Water Splitting Cycle

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