Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells

Kim, Jung‐Ju; Kim, In Sook; Cho, Tae Hyung; Lee, Kyu Back; Hwang, Soon Jung; Tae, Giyoong; Noh, Insup; Lee, Sang Hoon; Park, Yongdoo; Sun, Kyung

doi:10.1016/j.biomaterials.2006.11.050

Cited by 467 publications

(388 citation statements)

References 26 publications

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“…Other systems are too viscous for injection through fine-bore needles, which may limit the potential number of bone repair clinical applications and result in further damage to the target site (Michalek et al, 2010;Nassr et al, 2009). Other hydrogels, alternative to pNIPAM/HAP hydrogels for MSC delivery, have been reported; however, the viability of cells incorporated prior to gelation has not always been assessed (Couto et al, 2009) or the use of growth factors has been necessary to induce osteogenesis Martínez-Sanz et al, 2011;Kim et al, 2007;Kim et al, 2011;Liao et al, 2011;Martínez-Sanz et al, 2011;Na et al, 2007). The L-pNIPAM-co-DMAc hydrogel system described here is processed in a novel manner, whereby synthesising pNIPAM at 80 °C (i.e.…”

Section: Induction Of Osteogenic Differentiationmentioning

confidence: 99%

Hydroxyapatite nanoparticle injectable hydrogel scaffold to support osteogenic differentiation of human mesenchymal stem cells

Thorpe

Creasey²,

Sammon³

et al. 2016

eCM

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Bone loss associated with degenerative disease and trauma is a clinical problem increasing with the aging population. Thus, effective bone augmentation strategies are required; however, many have the disadvantages that they require invasive surgery and often the addition of expensive growth factors to induce osteoblast differentiation. Here, we investigated a Laponite  crosslinked, pNIPAMDMAc copolymer (L-pNIPAM-co-DMAc) hydrogel with hydroxyapatite nanoparticles (HAPna), which can be maintained as a liquid ex vivo, injected via narrowgauge needle into affected bone, followed by in situ gelation to deliver and induce osteogenic differentiation of human mesenchymal stem cells (hMSC). L-pNIPAMco-DMAc hydrogels were synthesised and HAPna added post polymerisation. Commercial hMSCs from one donor (Lonza) were incorporated in liquid hydrogel, the mixture solidified and cultured for up to 6 weeks. Viability of hMSCs was maintained within hydrogel constructs containing 0.5 mg/mL HAPna. SEM analysis demonstrated matrix deposition in cellular hydrogels which were absent in acellular controls. A significant increase in storage modulus (G') was observed in cellular hydrogels with 0.5 mg/mL HAPna. Semi-quantitative immunohistochemistry and histological analysis demonstrated that bone differentiation markers and collagen deposition was induced within 48 h, with increased calcium deposition with time. The thermally triggered hydrogel system, described here, was sufficient without the need of additional growth factors or osteogenic media to induce osteogenic differentiation of commercial hMSCs. Preliminary data presented here will be expanded on multiple patient samples to ensure differentiation is seen in these samples. This system could potentially reduce treatment costs and simplify the treatment strategy for orthopaedic repair and regeneration.

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Section: Induction Of Osteogenic Differentiationmentioning

confidence: 99%

Hydroxyapatite nanoparticle injectable hydrogel scaffold to support osteogenic differentiation of human mesenchymal stem cells

Thorpe

Creasey²,

Sammon³

et al. 2016

eCM

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“…HA is one of the main components of the extracellular matrix present in all connective tissues [20] and involved in a variety of biological functions [5,21], including direct receptor-mediated effects on cell adhesion, growth and migration [22], as well as acting as a signaling molecule in cell mortality [23], inflammation [24] or wound healing [25]. HA hydrogels have been used as vehicle for delivery of BMP-2 in vitro [5,8] and in vivo [21], as well for the delivery of biphosphonates [21].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Alginate and Hyaluronic Acid for Their Use in Bone Tissue Engineering

et al. 2012

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In this study, we compared the structural and physicochemical properties of different concentrations of alginate and high molecular weight hyaluronic acid (HA) hydrogels and their biocompatibility and bioactivity after long-term culture with MC3T3-E1 cells. Both hydrogels were biocompatible and supported long-term viability and cell proliferation. Alginate induced higher alkaline phosphatase (ALP) activity levels than HA. Calcium content was increased in concentration dependent manner in cells cultured with alginate compared to control. Culture with HA hydrogels reduced alkaline phosphatase (Alp), bone sialoprotein (Bsp) and osteocalcin (Oc), while alginate increased Oc mRNA levels. Unmodified alginate hydrogels supported osteoblast differentiation better than HA hydrogels, suggesting that alginates are more suitable for biomaterial applications in bone tissue engineering.

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“…Several controlled release systems promoting the delivery of GFs are combined in strategies with cells, with the goal of acting in a synergistic manner and promoting the enhancement of new tissue formation. Co-encapsulation of GFs and cells in hydrogels [2][3][4][5][6][7][8][9][10] and seeding of stem cells in microparticles or scaffolds loaded with bioactive agents [11][12][13][14][15][16][17][18] are among the most common TE strategies described in literature. Typically, GFs have been included in TE strategies through three main approaches: (1) incorporation within micro-and nano-particles, which can act as supplements for in vitro cell cultures or can be injected into the defect sites, stimulating in situ tissue healing.…”

Section: Single Gf Deliverymentioning

confidence: 99%

“…12,32-50 (3) Bioactive factors directly dispersed, immobilized, or adsorbed into the three-dimensional construct. 3,4,[6][7][8][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] The level of immobilization determines the release rate of GFs and consequently their effect on tissue formation. Several studies approach a particularly relevant immobilization method, mimicking native extracellular matrix (ECM), affinity-bound systems, through the inclusion of heparin domains on the structure, thus expecting an enhanced stability of the entrapped GF.…”

Section: Single Gf Deliverymentioning

confidence: 99%

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

Santo

Gomes²,

Mano³

et al. 2013

Tissue Engineering Part B: Reviews

100

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The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors.

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Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells

Cited by 467 publications

References 26 publications

Hydroxyapatite nanoparticle injectable hydrogel scaffold to support osteogenic differentiation of human mesenchymal stem cells

Hydroxyapatite nanoparticle injectable hydrogel scaffold to support osteogenic differentiation of human mesenchymal stem cells

Evaluation of Alginate and Hyaluronic Acid for Their Use in Bone Tissue Engineering

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

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