Regulating Bone Formation <i>via</i> Controlled Scaffold Degradation

Alsberg, Eben; Kong, Hyun Joon; Hirano, Yoshiaki; Smith, Michael L.; Albeiruti, A.; Mooney, David J.

doi:10.1177/154405910308201111

Cited by 312 publications

(237 citation statements)

References 32 publications

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“…Tailoring the degradation characteristics of a hydrogel may therefore be of critical importance in promoting endochondral ossification of engineered grafts [47][48][49][50]. Alternatively, or perhaps in conjunction, inflammatory cytokines may be leveraged to direct more efficient resorption of a large cartilaginous template [51].…”

Section: Discussionmentioning

confidence: 99%

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

et al. 2015

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Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) have been shown to generate bone in vivo by executing an endochondral program. This may hinder the use of MSCs for articular cartilage regeneration, but opens the possibility of using engineered cartilaginous tissues for large bone defect repair. Hydrogels may be an attractive tool in the scaling-up of such tissue engineered grafts for endochondral bone regeneration. In this study, we compared the capacity of different naturally derived hydrogels (alginate, chitosan, and fibrin) to support chondrogenesis and hypertrophy of MSCs in vitro and endochondral ossification in vivo. In vitro, alginate and chitosan constructs accumulated the highest levels of sGAG, with chitosan constructs synthesising the highest levels of collagen. Alginate and fibrin constructs supported the greatest degree of calcium accumulation, though only fibrin constructs calcified homogenously. In vivo, chitosan constructs facilitated neither vascularization nor endochondral ossification, and also retained the greatest amount of sGAG, suggesting it to be a more suitable material for the engineering of articular cartilage.Both alginate and fibrin constructs facilitated vascularization and endochondral bone formation as well as the development of a bone marrow environment. Alginate constructs accumulated significantly more mineral and supported greater bone formation in central regions of the engineered tissue. In conclusion, this study demonstrates the capacity of chitosan hydrogels to promote and better maintain a chondrogenic phenotype in MSCs and highlights the potential of utilizing alginate hydrogels for MSC-based endochondral bone tissue engineering applications.

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Section: Discussionmentioning

confidence: 99%

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

et al. 2015

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“…Alginate hydrogels modified through the addition of arginine-glycine-aspartic acid (RGD) to promote cell adhesion and gamma-irradiation to enhance degradation have been used for bone tissue engineering [2,3,36,39]. We have previously observed higher mineral content and biomechanical properties in critically sized femoral segmental defects treated with a perforated nanofiber mesh enclosing RGD-alginate and rhBMP-2 (NMA-rhBMP-2) hybrid delivery system at equivalent doses and with advantageous rhBMP-2 release kinetics as compared with ACS-rhBMP-2 [8,9,27,28].…”

Section: Introductionmentioning

confidence: 99%

Hydrogel-based Delivery of rhBMP-2 Improves Healing of Large Bone Defects Compared With Autograft

Krishnan

Priddy

Esancy

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Autologous bone grafting remains the gold standard in the treatment of large bone defects but is limited by tissue availability and donor site morbidity. Recombinant human bone morphogenetic protein-2 (rhBMP-2), delivered with a collagen sponge, is clinically used to treat large bone defects and complications such as delayed healing or nonunion. For the same dose of rhBMP-2, we have shown that a hybrid nanofiber mesh-alginate (NMA-rhBMP-2) delivery system provides longer-term release and increases functional bone regeneration in critically sized rat femoral bone defects compared with a collagen sponge. However, no comparisons of healing efficiencies have been made thus far between this hybrid delivery system and the gold standard of using autograft. Questions/purposes We compared the efficacy of the NMA-rhBMP-2 hybrid delivery system to morselized autograft and hypothesized that the functional regeneration of large bone defects observed with sustained BMP delivery would be at least comparable to autograft treatment as measured by total bone volume and ex vivo mechanical properties. Methods Bilateral critically sized femoral bone defects in rats were treated with either live autograft or with the NMA-rhBMP-2 hybrid delivery system such that each animal received one treatment per leg. Healing was monitored by radiography and histology at 2, 4, 8, and 12 weeks. Defects were evaluated for bone formation by longitudinal micro-CT scans over 12 weeks (n = 14 per group). The bone volume, bone density, and the total new bone formed beyond 2 weeks within the defect were calculated from micro-CT reconstructions and values compared for the 2-, 4-, 8-, and 12-week scans within and across the two treatment groups. Two animals were used for bone labeling with subcutaneously injected dyes at 4, 8, and 12 weeks followed by histology at 12 weeks to

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“…Appropriate adhesion peptide presentation has been shown to regulate bone and cartilage formation by transplanted cells, 48,54 and matching of the degradation rate of the synthetic ECM to the rate of tissue formation in these systems greatly increases the extent and rate of tissue formation. 55 Co-transplantation of appropriate cell populations in these materials has also been demonstrated to lead to the formation of multicomponent tissues, and in one example led to the formation of tissues structurally and functionally resembling growth plates. 56 While the materials will most directly control cells originally placed or recruited to the surface of the material, a number of reports indicate long-term control over both gene expression and tissue formation in vitro and in vivo, even though a small percentage of the cells is adherent to the material at those stages.…”

Section: Cell Instructive Polymers Adhesion Ligand Presentationmentioning

confidence: 99%

Regenerative medicine in orthopaedic surgery

Corsi

Schwarz

Mooney

et al. 2007

Journal Orthopaedic Research

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Regenerative medicine holds great promise for orthopaedic surgery. As surgeons continue to face challenges regarding the healing of diseased or injured musculoskeletal tissues, regenerative medicine aims to develop novel therapies that will replace, repair, or promote tissue regeneration. This review article will provide an overview of the different research areas involved in regenerative medicine, such as stem cells, bioinductive factors, and scaffolds. The potential use of stem cells for orthopaedic tissue engineering will be addressed by presenting the current progress with skeletal muscle-derived stem cells. As well, the development of a revascularized massive allograft will be described and will serve as a prototypic model of orthopaedic tissue engineering. Lastly, we will describe current approaches used to design cell instructive materials and how they can be used to promote and regulate the formation of bony tissue. ß

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Regulating Bone Formation via Controlled Scaffold Degradation

Cited by 312 publications

References 32 publications

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

Hydrogel-based Delivery of rhBMP-2 Improves Healing of Large Bone Defects Compared With Autograft

Regenerative medicine in orthopaedic surgery

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