Particle size effects on the bone formation of hydroxyapatite/ stem cell biocomposites

이종국,황규홍 한양대학교 세라믹연구소 2012 Journal of Ceramic Processing Research Vol.13 No.2

HA has a very similar chemical composition to the inorganic part of human hard tissue, such as bone and teeth, so most of bones form a direct chemical bonding to an HA implant without forming a collagen interface layer. In this study, we tried to observe the bone formation of the biocomposite mixed with stem cells and hydroxyapatite (HA) powders with different particle sizes in rabbit long-bone defects, and investigated the size effects of hydroxyapatite particles on the formation of new bone. From the radiological photographs of the implanted biocomposites into rabbits weekly for 8 weeks, nanoscale HA biocomposites show a higher bone formation rate than that of micrometer scale HA biocomposites. Added stem cells into the biocomposite induced homogeneous bone formation and enhanced the bone formation ability. Conclusively, nanoscale HA powder with stem cells is an adequate biocomposite for new bone formation in bone defects. HA has a very similar chemical composition to the inorganic part of human hard tissue, such as bone and teeth, so most of bones form a direct chemical bonding to an HA implant without forming a collagen interface layer. In this study, we tried to observe the bone formation of the biocomposite mixed with stem cells and hydroxyapatite (HA) powders with different particle sizes in rabbit long-bone defects, and investigated the size effects of hydroxyapatite particles on the formation of new bone. From the radiological photographs of the implanted biocomposites into rabbits weekly for 8 weeks, nanoscale HA biocomposites show a higher bone formation rate than that of micrometer scale HA biocomposites. Added stem cells into the biocomposite induced homogeneous bone formation and enhanced the bone formation ability. Conclusively, nanoscale HA powder with stem cells is an adequate biocomposite for new bone formation in bone defects.

Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using $^{18}F$-FDG PET/CT and $^{99m}Tc$-HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

Seo, Hyo-Jung,Choi, Yun-Jung,Kim, Hyun-Jeong,Jeong, Yong-Hyu,Cho, Arthur,Lee, Jae-Hoon,Yun, Mi-Jin,Choi, Hye-Jin,Lee, Jong-Doo,Kang, Won-Jun The Korea Society of Nuclear Medicine 2011 핵의학 분자영상 Vol.45 No.3

Purpose Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast-enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with or without soft tissue formation from HCC. Methods Of 4,151 patients with HCC, 263 patients had bone metastases. Eighty-five patients with bone metastasis from HCC underwent contrast-enhanced FDG PET/CT. Fifty-four of the enrolled subjects had recent $^{99m}Tc$-HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value ($SUV_{max}$) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow-up studies. Results Forty-seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft-tissue-formation group had more frequent bone pain (77 vs. 37%, p<0.0001), higher $SUV_{max}$ (6.02 vs. 3.52, p<0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non-soft-tissue-formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion-based analysis (98 vs. 53%, p=0.0015) and in patient-based analysis (100 vs. 80%, p<0.001). Conclusions Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast-enhanced PET/CT will be useful in finding and delineating softtissue- forming bone metastasis from HCC.

Extragraft bone formation after ACDF using two different bone remodeling algorithms

박원만,진용준,최청열 대한기계학회 2021 대한기계학회 춘추학술대회 Vol.2021 No.4

Extragraft bone formation is necessary to achieve solid union after spinal fusion including anterior discectomy and fusion. However, its mechanism is not well reported. In this study, extragraft bone graft was investigated based on the hypothesis that mechanical stimuli primarily cause extragraft bone formation. It was simulated using finite element analysis integrated into the developed Matlab codes. Matlab codes for simulating extragraft bone formation were developed using two different algorithms named the sequential and simultaneous algorithms. While the sequential algorithm simulates the layer-by-layer bone formations, the simultaneous algorithm predicted bone formation in the whole region of the pre-defined bone formation region. The results showed that sequential bone formation using the sequential algorithm showed good agreement to the medical observations. The results also showed the simultaneous algorithm may result in non-logical extragraft bone formation and it overestimates the bone formation. Based on the results the authors concluded that a sequential bone formation algorithm is necessary for simulating intramembranous ossification accelerated by mechanical stimuli similar to extragraft bone formation.

방사선 조사 망상골이 외방형 골형성에 미치는 영향

정미현,허익,권영혁,박준봉,정종혁,Chung, Mi-Hyun,Herr, Yeek,Kwon, Young-Hyuk,Park, Joon-Bong,Chung, Jong-Hyuk 대한치주과학회 2007 Journal of Periodontal & Implant Science Vol.37 No.4

The purpose of this study was to evaluate exophytically vertical bone formation in residual ridge of the beagle dog by the concept of guided bone regeneration with a titanium reinforced e-PTFE membrane combined with irradiated cancellous human bone. Twelve male beagle dogs(mean age 1.5 years and mean weight 12kg) were used for this study. The alveolar ridges after extraction of all mandibular premolars were surgically and horizontally removed. At 8 weeks after extractions, full-thickness flap was reflected and cortical bone was removed with round bur and copious irrigation. Rectangular parallelepiped(10mm in length, 5mm in width, and 4mm in height) bended with titanium-reinforced e-PTFE(TR e-PTFE) membrane was placed on the decorticated alveolar ridge, fixed with metal pins and covered with full-thickness flap and assigned as a control group. Test groups ere treated with TR e-PTFE membrane filled with irradiated cancellous human bone. Of twelve beagle dogs, four control dogs and four test dogs without membrane exposure to oral cavity were sacrificed at 8 and 16 weeks respectively. The surgical sites were dissected out, fixed in 4% buffered formaldehyde, dyed using a Villanueva staining technique, and processed for embedding in plastic resin. The cutting and grinding methods were routinely processed for histologic and histomophometric analyis of exophytic bone formation as well as statistical analysis. The results of this study were as follows: 1. Exophytic bone formation in the both of experimental groups was increased respectively after surgery from 23.40% at 8 weeks to 46.26% at 16 weeks in the control groups, from 40.23% at 8 weeks to 47.11% at 16 weeks in the test groups(p<0.05). 2. At 8 weeks after surgery, exophytic bone formation was made 40.23% in the test groups and 33.40% in the control groups. Exophytic bone formation was significantly made in the test group more than in the control group. At 16 weeks after surgery, exophytic bone formation was made 44.11% in the test groups and 46.26% in the control groups. Exophytic bone formation was made in the test groups more than in the control groups, but there was no statistically significant differences. 3. The membrane was fixed with metal pins to closely contact it to the bone surface. So, collapse and deviation of the membrane could be prevented and in growth of connective tissue also could be blocked from the periphery of the membrane. On the basis of these findings, wee suggest that intraoral experimental model for exophytic bone formation may be effective to evaluate the effect of bone graft material. And it indicates that combined use of membrane and ICB graft material is more effective than use of membrane only for exophytic bone formation.

The Effects of Synthetic Peptide Derived from hBMP-2 on Bone Formation in Rabbit Calvarial Defect

( Young Joon Cho ),( Shin Il Yeo ),( Jin Woo Park ),( Hong In Shin ),( Yong Chul Bae ),( Jo Young Suh ) 한국조직공학·재생의학회 2008 조직공학과 재생의학 Vol.5 No.3

The bone morphogenic proteins(BMPs) are multifunctional growth factors that belong to the TGF-β superfamily. Among BMPs, BMP-2 is known as the most effective cytokine. The present study evaluated effects of anorganic bovine bone graft material coated with synthetic peptide which corresponds to residues 73-92 of the knuckle epitope of hBMP-2 on bone formation in rabbit calvarial defects. The residues 73-92 of hBMP-2 was absorbed on anorganic bone mineral(ABM) by incubating ABM for 24 hrs. The rabbit calvarial defects were not filled at all(control group), and were filled ABM only(ABM group), ABM with residues 73-92 derived from hBMP- 2(ABM/hBMP-2P group) and ABM combined with hBMP-2(ABM/rhBMP-2 group). The groups were evaluated using histologic observation and histomorphometrc analysis at 4 and 8 weeks after healing. The higher osteoconductivity of the ABM/hBMP-2P and ABM/rhBMP-2 groups than the control and ABM only groups. Compared to the control group at 4 weeks after healing, the defects grafted with ABM/hBMP-2P and ABM/rhBMP-2 showed more active bone formation with a statistical significance(p<0.05). And ABM/hBMP-2P and ABM/rhBMP-2 showed a higher percentage bone length from the defect margins than control and ABM only groups at 4 weeks of healing with a statistical significance(p<0.05). ABM/hBMP-2P and ABM/rhBMP-2 may involve mainly initial bone healing and residues 73-92 of hBMP-2 could attribute to new bone formation. Based on the results of this study, anorganic bovine bone maybe a good carrier for peptide and anorganic bovine combined with residues 73-92 of hBMP-2 can increase the new bone formation in early stage in rabbit calvaria.

Fibrin Scalant 를 사용한 골자가이식에서 혈관신생에 관한 실험적 연구

권성택,김병건,김진환 大韓成形外科學會 1993 Archives of Plastic Surgery Vol.20 No.3

The effect of fibrin to wound healing has been studied and well documented : homostatic and adhesive effect and stimulatory effect on proliferation of fibroblast, formation of granulation tissue and neovascularization has been well known. In the process of bone healing, action of fibrin has been reported to stimulate the formation of granulation tissue, new vessels and new bone, but there have been many reports contrary to the effects of fibrin. Authors used New Zealand white rabbit as an experimental animal. Bone grafts were harvested from right and left parietal bone and onlay grafts were performed to both sides of frontal bone. Fibrin sealant was applied to experimental group and was not applied on the control group. Both groups were sacrificed after 1, 2, 3, 4, and 8 weeks respectively and results were examined and compared after H&E stain and Masson's trichrome stain by light microscope. The group using fibrin sealant showed new bone formation on 1st week and new vessel formation on 2nd week, and vessels were numerous and had thick walls. And there were dense bony connections between donor bone and recipient bone. In calvarial bone graft which is most commonly used in plastic and reconstructive surgery, especially in infected and extensively injured wound which might compromise blood supply, we believe that bone graft using fibrin sealant can stimulate vascularization and new bone formation and therefore enhance the survival of bone graft.

Effect of Cytokines and bFGF on the Osteoclast Differentiation Induced by 1α,25-(OH)<SUB>2</SUB>D<SUB>3</SUB> in Primary Murine Bone Marrow Cultures

Han-Jung Chae,Jang-Sook Kang,Byung-Gwan Bang,Seoung-Bum Cho,Jo-IL Han,Joo-Young Choi,Hyung-Min Kim,Soo-Wan Chae,Hyung Ryong Kim 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.6

<P> Bone is a complex tissue in which resorption and formation continue throughout life. The bone tissue contains various types of cells, of which the bone forming osteoblasts and bone resorbing osteoclasts are mainly responsible for bone remodeling. Periodontal disease represents example of abnormal bone remodeling. Osteoclasts are multinucleated cells present only in bone. It is believed that osteoclast progenitors are hematopoietic origin, and they are recruited from hematopoietic tissues such as bone marrow and circulating blood to bone. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells produce cytokines that can affect osteoclast formation. In vitro model systems using bone marrow cultures have demonstrated that IL-1β, IL-3, TNF-α, bFGF can stimulate the formation of osteoclasts. In contrast, IL-4 inhibits osteoclast formation. Knowledge of cytokines and bFGF that affect osteoclast formation and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as periodontal disease, osteoporosis and Paget s disease.

스트렙토조토신 유도 당뇨백서의 골조직 재생에 흡수성 차폐막이 미치는 영향

양병근,이학철,이지영,손강배,설양조,이상철,계승범,정종평,한수부,Yang, Byung-Kun,Lee, Hak-Churl,Lee, Ji-Young,Son, Kang-Bae,Seol, Yang-Jo,Lee, Sang-Cheol,Kye, Seung-Beom,Chung, Chong-Pyoung,Han, Soo-Boo 대한치주과학회 2000 Journal of Periodontal & Implant Science Vol.30 No.2

The purpose of this study is to evaluate the effects of bioresorbable membranes in guided bone regeneration of streptozotocin induced diabetic rats. 50 Sprague-Dawley rats were randomly categorized into 4 groups: Group 1 & 2 had 10 normal rats each and group 3 & 4 included 15 streptozotocin induced diabetic rats each. Defect measuring 7mm in diameter was formed on every rat calvarium. No membrane was used in groups 1 & 3 and membranes were used in groups 2 & 4. The rates were sacrificed at 2 and 4 weeks after defect formation. Routine histological specimens were prepared. Masson-trichrome and HE stain were done before light microscopy. Guided regenerative potential was evaluated by measuring the amount of new bone formation in the calvarial defect by histomorphometry. Following results were obtained. 1. New bone formation in the diabetic groups was significantly less that than in the normal groups regardless of membrane use(p<0.05). 2. In the comparison of new bone formation in the normal groups, membrane group showed significantly more bone formation(p<0.1). 3. When the amount of new bone formation was compared in the diabetic groups, more bone was formed in the membrane groups but the difference was not statistically significant.4. In the normal groups the amount of new bone formation was significantly greater at 4 weeks compared to that at2 weeks(p<0.05) but amount of bone regeneration at 4 weeks was not significantly greater than that at 2 weeks in both diabetic groups.

아데노바이러스 벡터를 이용한 BMP-2와 FGF-2의 동시 발현이 골형성에 미치는 영향

송상훈,장원구,김선헌,국민석,김옥준,김인애,박인규,고정태 한국조직공학과 재생의학회 2009 조직공학과 재생의학 Vol.6 No.13

FGF-2 and BMPs are expressed simultaneously during the embryonic bone development and repair of fractured bone. Delivery of BMP-2 peptide and gene has been evaluated for a therapeutic bone regeneration. However, low efficacy and short half -life of BMP-2 peptide have limited their clinical uses. This study was to determine the effects of BMP-2 and FGF-2 combination on bone formation with the adenoviral BMP-2 and FGF-2 gene delivery. Adenoviruses (Ad) expressing BMP-2 or FGF-2 were constructed under the CMV promoter, and characterized. AdBMP-2 dose-dependantly induced BMP-2 peptide expression in BLK cells, and increased alkaline phosphatase (ALP) activity in C2C12. AdFGF-2 also induced FGF-2 peptide expression in a dose-dependent manner. Proliferation of C3H10T1/2, ST-2 and MC3T3-E1 cell was stimulated by AdFGF-2 alone treatment, but ALP activity of the cells was inhibited. To evaluate the effect of BMP-2 and FGF-2 combination on bone formation, AdBMP-2 (100 moi) and/or AdFGF-2 (100 or 200 moi) were transduced into BLK fibroblast cells, and then the cells were transferred into subcutaneous spaces with collagen hydrogel in mice. Microradiographic analysis, biochemical assays and histology showed AdBMP-2 and AdFGF-2 combination produced less bone than AdBMP-2 alone at 2 weeks after implantation. In addition, AdBMP-2/AdFGF-2 combination group had less ALP activity and concentrations of inorganic phosphate and calcium in implants than AdBMP-2 treated group. These results suggest that FGF-2 may stimulate the proliferation of osteoblastic cells, but inhibit the BMP-2 induction of osteoblast differentiation and bone formation. FGF-2 and BMPs are expressed simultaneously during the embryonic bone development and repair of fractured bone. Delivery of BMP-2 peptide and gene has been evaluated for a therapeutic bone regeneration. However, low efficacy and short half -life of BMP-2 peptide have limited their clinical uses. This study was to determine the effects of BMP-2 and FGF-2 combination on bone formation with the adenoviral BMP-2 and FGF-2 gene delivery. Adenoviruses (Ad) expressing BMP-2 or FGF-2 were constructed under the CMV promoter, and characterized. AdBMP-2 dose-dependantly induced BMP-2 peptide expression in BLK cells, and increased alkaline phosphatase (ALP) activity in C2C12. AdFGF-2 also induced FGF-2 peptide expression in a dose-dependent manner. Proliferation of C3H10T1/2, ST-2 and MC3T3-E1 cell was stimulated by AdFGF-2 alone treatment, but ALP activity of the cells was inhibited. To evaluate the effect of BMP-2 and FGF-2 combination on bone formation, AdBMP-2 (100 moi) and/or AdFGF-2 (100 or 200 moi) were transduced into BLK fibroblast cells, and then the cells were transferred into subcutaneous spaces with collagen hydrogel in mice. Microradiographic analysis, biochemical assays and histology showed AdBMP-2 and AdFGF-2 combination produced less bone than AdBMP-2 alone at 2 weeks after implantation. In addition, AdBMP-2/AdFGF-2 combination group had less ALP activity and concentrations of inorganic phosphate and calcium in implants than AdBMP-2 treated group. These results suggest that FGF-2 may stimulate the proliferation of osteoblastic cells, but inhibit the BMP-2 induction of osteoblast differentiation and bone formation.

탈회동결건조골이 수직골 형성에 미치는 영향

박주희,권영혁,박준봉,정종혁,신승일,허익,Park, Ju-Hee,Kwon, Young-Hyuk,Park, Joon-Bong,Chung, Jong-Hyuk,Shin, Seung-Il,Herr, Yeek 대한치주과학회 2008 Journal of Periodontal & Implant Science Vol.38 No.1

Purpose: The purpose of this study was to evaluate exophytically vertical bone formation in the mandibular premolar area of beagle dogs by the concept of guided bone regeneration with a titanium reinforced e-PTFE membrane combined with human demineralized freeze-dried bone. Materials and Methods: Four one-year old beagle dogs were divided into control and experimental group. All mandibular premolars were extracted and surgical vertical defects of 5 mm in height were created in the extracted sockets. At 8 weeks after the extraction, TR e-PTFE membrane sized with 8 mm in length, 5 mm in width, and 4 mm in height was placed on the decorticated mandible, fixed with metal pins and covered with full-thickness flap and assigned as control group. In experimental group, decorticated mandibule was treated with TR e-PTFE membrane and human demineralized freeze-dried bone. The animals were sacrificed at 16 weeks after the regenerative surgery, and new bone formation was assessed by histomorphometric as well as statistical analysis. Results: Average of new bone formation was 38% in the control group, whereas was 25% in the experimental group (p<0.05). Average of connective tissue formation was 42% in the experimental group, whereas was 30% in the control group (p<0.05). The lamellar bone formation with haversian canals was observed in the both groups. In the experimental group, the particles of human demineralized freeze-dried bone were observed after 16 weeks and complete resorption of graft was not observed. Conclusion: On the basis of these findings, we conclude that titanium reinforced e-PTFE membrane may be used alone for vertical guided bone regeneration, but demineralized freeze-dried bone has no additional effect on vertical guided bone regeneration.