Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering <i>In Vivo</i>

Dennis, S. Connor; Berkland, Cory; Bonewald, Lynda F.; Detamore, Michael S.

doi:10.1089/ten.teb.2014.0419

Cited by 75 publications

(84 citation statements)

References 118 publications

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“…Different biomolecules are released at different times to mimic as closely as possible the situation of the natural ECM [Luo and Shoichet, 2004]. However, the native ECM consists of a very complex arrangement of collagen, glycoproteins, and a variety of growth-promotive factors which continuously change in a real regeneration process; thus the replication of the same ECM is almost unthinkable [Dennis et al, 2015]. Recently, investigations have focused on designing new vehicles by using the decellularized matrices (natural ECM).…”

Section: Delivery Of Cells Within a 3d Dynamic Environmentmentioning

confidence: 99%

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

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

291

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: Delivery Of Cells Within a 3d Dynamic Environmentmentioning

confidence: 99%

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

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

291

204

View full text Add to dashboard Cite

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“…In particular, utilization of cartilage anlage has resulted in the ability to form bone in vivo. [2][3][4][5][6][7] Among these strategies, the use of hypertrophic chondrocytes, the cell that orchestrates endochondral ossification, appears particularly promising as the maturation from chondrocytes to hypertrophic chondrocytes resulted in significantly more bone formation. 8 The hypertrophic chondrocyte constructs have shown an ability to create maturing bone in vitro, which subsequently developed vasculature and bone marrow following subcutaneous implantation, 6,9 and facilitated healing of calvarial 10,11 and long bone 12 defects.…”

Section: Introductionmentioning

confidence: 99%

Perfusion Enhances Hypertrophic Chondrocyte Matrix Deposition, But Not the Bone Formation

Bernhard

Hulphers

Rieder

et al. 2018

Tissue Engineering Part A

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Perfusion bioreactors have been an effective tool in bone tissue engineering. Improved nutrient delivery and the application of shear forces have stimulated osteoblast differentiation and matrix production, allowing for generation of large, clinically sized constructs. Differentiation of hypertrophic chondrocytes has been considered an alternative strategy for bone tissue engineering. We studied the effects of perfusion on hypertrophic chondrocyte differentiation, matrix production, and subsequent bone formation. Hypertrophic constructs were created by differentiation in chondrogenic medium (2 weeks) and maturation in hypertrophic medium (3 weeks). Bioreactors were customized to study a range of flow rates (0-1200 μm/s). During chondrogenic differentiation, increased flow rates correlated with cartilage matrix deposition and the presence of collagen type X. During induced hypertrophic maturation, increased flow rates correlated with bone template deposition and the increased secretion of chondroprotective cytokines. Following an 8-week implantation into the critical-size femoral defect in nude rats, nonperfused constructs displayed larger bone volume, more compact mineralized matrix, and better integration with the adjacent native bone. Therefore, although medium perfusion stimulated the formation of bone template in vitro, it failed to enhance bone regeneration in vivo. However, the promising results of the less developed template in the critical-sized defect warrant further investigation, beyond interstitial flow, into the specific environment needed to optimize hypertrophic chondrocyte-based constructs for bone repair.

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“…Incorporating natural extracellular matrix (ECM) into biomaterial systems provides relevant biochemical and biophysical guidance cues to direct regeneration in bone, cartilage, nerve, and cardiac tissue [22–26]. Additionally, it is now a common practice in tissue engineering to exploit the capability of ECM to sequester and release tissue morphogens, but there are few strategies in the literature utilizing ECM to achieve controlled release of hydrophobic small molecules [27–29].…”

Section: Introductionmentioning

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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Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

Cited by 75 publications

References 118 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?

Perfusion Enhances Hypertrophic Chondrocyte Matrix Deposition, But Not the Bone Formation

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

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