Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers

Okada, Takao; Horiuchi, Hiroshi; Ōta, Hiroshi; Takahashi, J.; Murakami, Narumichi; Nawata, Masashi; Kojima, Sayuri; Nozaki, Kazutoshi; Takaoka, Kunio

doi:10.1016/s8756-3282(03)00028-0

Cited by 96 publications

(67 citation statements)

References 20 publications

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“…One common method of BMPs delivery is via biodegradable polymeric scaffolds or hydrogel. [166][167][168] BMPs have been tested in preclinical and clinical studies, showing their definite potential in osteoinduction and have been FDA-approved for clinical use in open fracture of long bones, non-unions, and vertebral arthrodesis. 169,170 However, the transition into clinical studies has had only mild success and relies on large doses of BMPs for bone formation.…”

Section: Chemical Effectors In Synthetic Bone Scaffoldsmentioning

confidence: 99%

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Porter

Ruckh

Popat

2009

Biotechnology Progress

674

499

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Critical‐sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue‐engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical‐sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF‐βs, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009

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Section: Chemical Effectors In Synthetic Bone Scaffoldsmentioning

confidence: 99%

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Porter

Ruckh

Popat

2009

Biotechnology Progress

674

499

View full text Add to dashboard Cite

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“…The importance of these scaffolds is shown by the fact that human tissue development is driven by surface adhesions and cellular contacts. [8][9][10][11][12] Therefore, we decided to perform this research with the aim to obtain a complete bone tissue formation. For this reason we studied the differentiation process leading to in vitro woven bone formation in order to better understand the mechanisms involved as well as bone tissue formation after transplantation in vivo.…”

mentioning

confidence: 99%

Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation

d’Aquino¹,

Graziano²,

et al. 2007

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Stromal stem cells from human dental pulp (SBP-DPSCs) were used to study osteogenic differentiation in vitro and in vivo. We previously reported that SBP-DPSCs are multipotent stem cells able to differentiate into osteoblasts, which synthesize threedimensional woven bone tissue chips in vitro. In this study, we followed the temporal expression pattern of specific markers in SBP-DPSCs and found that, when differentiating into osteoblasts, they express, besides osteocalcin, also flk-1 (VEGF-R2). In addition, 30% of them expressed specific antigens for endothelial cells, including CD54, von-Willebrand (domain 1 and 2), CD31 (PECAM-1) and angiotensin-converting enzyme. Interestingly, we found endotheliocytes forming vessel walls, observing that stem cells synergically differentiate into osteoblasts and endotheliocytes, and that flk-1 exerts a pivotal role in coupling osteoblast and endotheliocyte differentiation. When either SBP-DPSCs or bone chips obtained in vitro were transplanted into immunocompromised rats, they generated a tissue structure with an integral blood supply similar to that of human adult bone; in fact, a large number of HLA-1 þ vessels were observed either within the bone or surrounding it in a periosteal layer. This study provides direct evidence to suggest that osteogenesis and angiogenesis mediated by human SBP-DPSCs may be regulated by distinct mechanisms, leading to the organization of adult bone tissue after stem cell transplantion.

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“…PLA-PEG/OP-1 composites were prepared as described previously [25]. Briefly, 10 mg of the polymer was liquefied in 50 lL acetone and mixed with 3, 10, or 30 lg OP-1.…”

Section: Methodsmentioning

confidence: 99%

“…Atelocollagen is a well-established BMP carrier, and has already been used clinically. PLA-PEG [20], one of the synthetic polymers, has been reported as a potent carrier for BMPs [23,25,26]. Although all of these materials can induce bone formation at ectopic and orthotopic sites, none of them has achieved widespread use because of disadvantages, such as the potential risk of disease transmission, fragility, stickiness, and difficulty in obtaining approval for clinical use [1,4,5,14].…”

Section: Introductionmentioning

confidence: 99%

Synthetic Alginate is a Carrier of OP-1 for Bone Induction

Nanno

Sugiyasu

Daimon

et al. 2009

Clin Orthop Relat Res

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Bone morphogenetic proteins (BMPs) can induce bone formation in vivo when combined with appropriate carriers. Several materials, including animal collagens and synthetic polymers, have been evaluated as carriers for BMPs. We examined alginate, an approved biomaterial for human use, as a carrier for BMP-7. In a mouse model of ectopic bone formation, the following four carriers for recombinant human OP-1 (BMP-7) were tested: alginate crosslinked by divalent cations (DC alginate), alginate crosslinked by covalent bonds (CB alginate), Type I atelocollagen, and poly-D,L-lactic acid-polyethyleneglycol block copolymer (PLA-PEG). Discs of carrier materials (5-mm diameter) containing OP-1 (3-30 lg) were implanted beneath the fascia of the back muscles in six mice per group. These discs were recovered 3 weeks after implantation and subjected to radiographic and histologic studies. Ectopic bone formation occurred in a dosedependent manner after the implantation of DC alginate, atelocollagen, and PLA-PEG, but occurred only at the highest dose implanted with CB alginate. Bone formation with DC alginate/OP-1 composites was equivalent to that with atelocollagen/OP-1 composites. Our data suggest DC alginate, a material free of animal products that is already approved by the FDA and other authorities, is a safe and potent carrier for OP-1. This carrier may also be applicable to various other situations in the orthopaedic field.

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Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers

Cited by 96 publications

References 20 publications

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation

Synthetic Alginate is a Carrier of OP-1 for Bone Induction

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