Poly(α-hydroxy acid) carrier for delivering recombinant human bone morphogenetic protein-2 for bone regeneration

Hollinger, Jeffrey O.; Mayer, Michael H.; Buck, David C.; Zegzula, H. Daniel; Ron, Eyal; Smith, Justin S.; Jin, Lisa; Wozney, John M.

doi:10.1016/0168-3659(95)00183-2

Cited by 39 publications

(19 citation statements)

References 55 publications

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“…36 Moreover, crystallinity, surface phenomena of texture, charge and chemistry, and biodegradation rates are important features. 22 Optimization of cell density, BMP dosing, and chemical and physical properties of the scaffold must interact with the recipient site to promote the desired clinical outcome. In terms of clinical outcome, the bone autograft is the current standard against which bone biomimetic therapies will be judged.…”

Section: Discussionmentioning

confidence: 99%

“…[19][20][21] Moreover, PL is a well-characterized homopolymer and offers the advantages of synthesis and postsynthesis reproducibility, paramount to clinical success in satisfying consistency of responses. 22,23 In addition, by adding type I collagen to the PL, we predicted enhancement of cell attachment and BMP distribution, 8,[24][25][26][27] thereby fortifying fundamental properties for a tissue-engineered bone biomimetic. Therefore, our hypotheses for this study were the biomimetic composite PL and type I collagen (PLC)/ OPCs/recombinant human BMP-2-(rhBMP-2) would promote more new bone formation in critical-sized defects (CSDs) than the other treatments and bone formation would be time dependent.…”

Section: Introductionmentioning

confidence: 99%

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Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats

Winn

Schmitt

Buck

et al. 1999

J. Biomed. Mater. Res.

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A tissue-engineered bone biomimetic device was developed to regenerate calvaria critical-sized defects (CSDs) in athymic rats. Well-documented evidence clearly confirms that left untreated, CSDs will not spontaneously regenerate bone. To accomplish regeneration, four candidate treatments were assessed: porous poly(D,L-lactide) and type I collagen (PLC), PLC and human osteoblast precursor cells (OPCs) at 2 x 10(5) (PLC/OPCs), PLC and 50 microg of recombinant human bone morphogenetic protein-2 (PLC/rhBMP-2), and PLC/OPCs/rhBMP-2 (the bone biomimetic device). The hypotheses for this study were PLC/OPCs/rhBMP-2 would promote more new bone formation in CSDs than the other treatments and the amount of bone formation would be time dependent. To test the hypotheses, outcomes from treatments were measured at 2 and 4 weeks postoperatively by radiomorphometry for percent radiopacity and by histomorphometry for square millimeters of new bone formation. Data were analyzed by analysis of variance and Fisher's protected least significant difference for multiple comparisons with p< or = 0.05. At 2 and 4 weeks, radiomorphometric data revealed PLC/rhBMP-2 and PLC/OPCs/rhBMP-2 promoted significantly more radiopacity than either PLC or PLC/OPCs. Histomorphometry data at 2 and 4 weeks indicated significantly more new bone formation for PLC/rhBMP-2, PLC/OPCs/rhBMP-2, and PLC/OPCs compared to PLC. By 4 weeks, PLC/OPCs/rhBMP-2 and PLC/rhBMP-2 had regenerated the CSDs with more new bone than the other treatments; the quantity of bone at 4 weeks for these treatments was greater than at 2 weeks.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats

Winn

Schmitt

Buck

et al. 1999

J. Biomed. Mater. Res.

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“…44 Recombinant BMP-2 was delivered by a poly( a -hydroxy acid) carrier for calvarial regeneration. 45 Copolym ers of polylactic and plyglycolic acid, or carrier for BMP-2 with excellent bone formation in a nonunion model in rabbit ulna, were used.…”

Section: Biomimetic Biomaterialsmentioning

confidence: 99%

Morphogenesis and Tissue Engineering of Bone and Cartilage: Inductive Signals, Stem Cells, and Biomimetic Biomaterials

2000

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Morphogenesis is the developmental cascade of pattern formation, body plan establishment, and the architecture of mirror-image bilateral symmetry of many structures and asymmetry of some, culminating in the adult form. Tissue engineering is the emerging discipline of design and construction of spare parts for the human body to restore function based on principles of molecular developmental biology and morphogenesis governed by bioengineering. The three key ingredients for both morphogenesis and tissue engineering are inductive signals, responding stem cells, and the extracellular matrix. Among the many tissues in the human body, bone has considerable powers for regeneration and is a prototype model for tissue engineering based on morphogenesis. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and permitted the isolation of bone morphogens. Although it is traditional to study morphogenetic signals in embryos, bone morphogenetic proteins (BMPs), the inductive signals for bone, were isolated from demineralized bone matrix from adults. BMPs and related cartilage-derived morphogenetic proteins (CDMPs) initiate, promote, and maintain chondrogenesis and osteogenesis and have actions beyond bone. The symbiosis of bone inductive and conductive strategies are critical for tissue engineering, and is in turn governed by the context and biomechanics. The context is the microenvironment, consisting of extracellular matrix, which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion proteins including fibronectins. Thus, the rules of architecture for tissue engineering are an imitation of the laws of developmental biology and morphogenesis, and thus may be universal for all tissues, including bones and joints.

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“…The rhBMP-2/ PLGA capsules could be superior in that the release profile is variable by changing the methodology of the encapsulation and that they are ready to use without any complex preparation at the time of operation. A complete quantitative comparison between this study and that of Hollinger et al 20 is not easy to describe because of differences in the observation period and operative conditions. In this study, both radiographic and DXA examination showed definite bone restorative activity using the rhBMP-2/PLGA capsules.…”

Section: Discussionmentioning

confidence: 92%

“…Recently, Hollinger et al reported the successful bone regenerative effects of rhBMP-2 when combined with particulate PLG and carboxymethyl cellulose (CMC) or autogenous blood at 8 weeks postoperatively in a rabbit model. 20 They applied CMC or autogenous blood clot as a binder between PLG particles and rhBMP-2, intending for the clot to provide for the slow release of the rhBMP-2 from implants, and reported good radiographic and histological results. Their reason for providing controlled delivery of rhBMP-2 was the same as that which we pursued in our study.…”

Section: Discussionmentioning

confidence: 98%

Restoration of segmental bone defects in rabbit radius by biodegradable capsules containing recombinant human bone morphogenetic protein-2

Mori

Isobe

Yamazaki³

et al. 2000

J. Biomed. Mater. Res.

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Recombinant human bone morphogenetic protein-2 (rhBMP-2) was encapsulated in biodegradable poly(DL-lactide-co-glycolide) (PLGA) capsules to regenerate bone by controlling the release rate of rhBMP-2. The rhBMP-2/PLGA capsules containing 12 microg of rhBMP-2 were implanted in seven 15-mm segmental defects of rabbits radii to examine the healing capacity of the rhBMP-2/PLGA capsules. For the control group, four segmental defects were left empty and two were implanted with ghost PLGA capsules. Healing of the defects was followed for 24 weeks and periodically evaluated by radiographs and histological examination. Mechanical testing was applied to three regenerated bone samples at 24 weeks postoperatively when the mature cortex was observed. Mechanical properties of regenerated bone were not significantly different from normal intact bone statistically. Histologically, the rhBMP-2/PLGA capsules disappeared completely during the process of bone regeneration. These results increased possibilities for clinical application of rhBMP-2/PLGA capsules.

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Poly(α-hydroxy acid) carrier for delivering recombinant human bone morphogenetic protein-2 for bone regeneration

Cited by 39 publications

References 55 publications

Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats

Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats

Morphogenesis and Tissue Engineering of Bone and Cartilage: Inductive Signals, Stem Cells, and Biomimetic Biomaterials

Restoration of segmental bone defects in rabbit radius by biodegradable capsules containing recombinant human bone morphogenetic protein-2

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