Enhanced Bone Bonding of the Hydroxyapatite/β‐Tricalcium Phosphate Composite by Electrical Polarization in Rabbit Long Bone

A review of the osteogenic cell activity and new bone growth in the regions bordering negatively charged surfaces of polarized Hydroxyapatite/β‐tricalcium phosphate (HA/TCP) composites implanted in the long bone in rabbits was conducted. Polarized and non‐polarized HA/TCP specimens were implanted into the right and left femoral condyle, respectively (each n = 10). After 3 and 6 weeks, five rabbits were sacrificed in each group, and histological analysis was administered. Large cuboidal‐shaped osteoblastic cells were predominantly observed lining the newly formed bone on the negatively charged surface (N‐surface) in the polarized HA/TCP implants. The TRAP‐positive multinucleated cells were observed extensively in the newly formed bone on the N‐surfaces compared with the 0‐surface and adhered directly to the HA/TCP composite. The bone area (B.Ar) value, newly formed bone area contacting the implant, and contact length (C.Le) value, percentage length of newly formed bone directly attaching to the implant, on both the 0‐ and N‐surface increased significantly with time in each group. Both the B.Ar and C.Le value on the N‐surface were significantly greater than those on the 0‐surface after 3 and 6 weeks. The number of TRAP‐positive cells/total length value on the N‐surface was significantly greater than that on the 0‐surface after 3 and 6 weeks postoperatively. It is hypothesized that electrical charge acquired by electrical polarization treatment may modify the biochemical and biophysical processes of the osteogenic cells, resulting in enhanced new bone formation and direct bonding between the recipient bone and implants.     

Porous hydroxyapatite and tricalcium phosphate cylinders with two different pore size ranges implanted in the cancellous bone of rabbits. A comparative histomorphometric and histologic study of bony ingrowth and implant substitution

To investigate the histophysiology of implant degradation, hydroxyapatite and tricalcium phosphate cylinders with a diameter of 3 mm were implanted in the cancellous bone of the distal femur and the proximal tibia of 15 New Zealand White rabbits for up to six months. All implants had a homogeneous pore distribution and a porosity of 60%. Ceramics with a pore size range of 50-100 micron and 200-400 micron were compared. Morphometric analysis showed that up to 85.4% of the originally implanted tricalcium phosphate was degraded after six months, whereas the volume reduction of the hydroxyapatite was only 5.4% after the same period. Within the first months bone and tissue ingrowth and implant resorption occurred at a higher rate in the smaller-pored tricalcium phosphate than in the larger-pored material. Hydroxyapatite cylinders with small pores were totally infiltrated by bone or bone marrow after four months, whereas in the larger-pored hydroxyapatite implants tissue did not penetrate all pores after six months and the amount of bone within the implant was small. Scanning electron microscopy of the material before implantation revealed the existence of numerous pore interconnections with diameters of about 20 micron in the smaller-pored ceramics. Such interconnections were rare in the larger-pored implants. The pore interconnections seem to promote vascular and tissue ingrowth and consequently the initial rate of implant resorption. Implant resorption is an active process and involves two different cell types. Acid phosphatase-positive osteoclast-like cells suggesting active resorption adhere directly to the surface, especially in tricalcium phosphate implants. Clusters of macrophages tightly packed with granular material are found in the pores and along the perimeter of all implant cylinders. They may play an active role in the intracellular degradation of small detached ceramic particles.     

Effects of hydroxyapatite tricalcium phosphate coating and intracancellous placement on bone ingrowth in titanium fibermetal implants

The purpose of this study was to compare the host—bone response to hydroxyapatite/tricalcium phosphate (HA/TCP)-coated and noncoated titanium fibermetal implants placed in a load-sharing cancellous bone environment of the distal femurs of rabbits. The influence of implantation site was also investigated by comparing these intracancellous implants with intramedullary implants evaluated in a previous study. Three parameters were measured: percentage implant perimeter surface length in contact with new bone, percentage internal fibermetal surface length in contact with ingrown bone, and percentage of available pore space filled with bone. The HA/TCP coating significantly accelerated and increased bone ongrowth, new bone formation on the perimeter and internal surface of the implants. This effect was evident as early as 2 weeks after implantation. In contrast, there was no difference between HA/TCP-coated and noncoated implants in the bone ingrowth parameter, percentage of available pore space filled with bone, or pull-out strength. Scanning electron microscopy in the backscatter mode demonstrated that new bone formed directly onto the HA/TCP-coated fibers and did not usually form directly on noncoated fibers. Analysis of fluorochrome labeling revealed that bone formation in weeks 1 through 4 was primarily woven and there-after lamellar. Compared with intramedullary placement, intracancellous placement significantly accelerated the apposition of bone to the perimeter and internal surface of HA/TCP-coated implants and both accelerated and increased bone ingrowth as a percentage of available pore volume. These data show that the host response to titanium fibermetal implants is influenced both by HA/TCP coating and by the implantation site.     

Fresh bone marrow introduction into porous scaffolds using a simple low‐pressure loading method for effective osteogenesis in a rabbit model

Recent advances in tissue engineering techniques have allowed porous biomaterials to be combined with osteogenic cells for effective bone regeneration. We developed a simple low‐pressure cell‐loading method using only syringes and stopcocks, and examined the effect of this method on osteogenesis when applied to the combination of highly porous β‐tricalcium phosphate (β‐TCP) and fresh autologous bone marrow. Both block and granule β‐TCP scaffolds were used to prepare implants in three different ways: without bone marrow as a control, with bone marrow that was allowed to penetrate spontaneously under atmospheric pressure (AP group), and with bone marrow that was seeded under low pressure (ULP group). These implants were transplanted into rabbit intramuscular sites, and the samples were examined biologically and histologically. The penetration efficiency of the block implants after marrow introduction was significantly higher in the ULP group than in the AP group. In the transplanted block samples, alkaline phosphatase activity was significantly higher in the ULP group at 2 weeks after implantation, and significantly more newly formed bone was observed in the ULP group at both 5 and 10 weeks compared with the AP group. Similar results were observed even in the experiment using β‐TCP granules, which are smaller than the blocks and frequently used clinically. Because of its convenience and safety, this low‐pressure method might be a novel, effective treatment to promote osteogenesis with bone marrow in clinical bone reconstruction surgeries. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1–7, 2009     

Massive bone reconstruction with heat‐treated bone graft loaded autologous bone marrow‐derived stromal cells and β‐tricalcium phosphate composites in canine models

Bone marrow‐derived stromal cells (BMSCs) contain mesenchymal stem cells that are capable of forming various mesenchymal tissues. We hypothesized that BMSCs and β‐tricalcium phosphate (β‐TCP) composites would promote the remodeling of large‐sized autologous devitalized bone grafts; therefore, the aim of this study was to evaluate the effects of the composites on the remodeling of autologous devitalized bone grafts. Autologous BMSCs cultured in culture medium containing dexamethasone (10^?7 M) were loaded into porous β‐TCP granules under low‐pressure. Theses BMSC/TCP composites were put into the bone marrow cavity of autologous heat‐treated bone (femoral diaphysis, 65‐mm long, 100°C, 30 min) and put back to the harvest site. In the contralateral side, β‐TCP without BMSC were used in the same manner as the opposite side as the control. Treatment with the BMSC/TCP composites resulted in a significant increase in thickness, bone mineral density, and matured bone volume of the cortical bone at the center of the graft compared to the control. Histological analysis showed matured regenerated bone in the BMSC loaded group. These results indicate that BMSC/TCP composites facilitated bone regeneration and maturation at the graft site of large‐sized devitalized bone. This method could potentially be applied for clinical use in the reconstruction of large bone defects such as those associated with bone tumors. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1308–1316, 2013

     

新型生物活性陶瓷复合人工骨成骨效应的实验研究

目的　探讨新型生物活性陶瓷复合材料成骨效应 ,为人工骨替代材料临床应用提供依据。　方法　小鼠 96只 ,随机分为 4组 ,每组 2 4只。采用具有诱导活性的骨形成蛋白 (bone morphogenetic protein,BMP)分别与羟基磷灰石 (hydroxyapatite,HA)、磷酸三钙 (tricalcium phosphate,TCP)、胶原复合羟基磷灰石 (collagen HA,CHA)及氟化羟基磷灰石 (fluoridated HA,FHA)复合 ,将 4种复合材料 (HA/ BMP,TCP/ BMP,CHA/ BMP及 FHA/ BMP)分别植入 4组小鼠左侧股部肌肉内为实验侧 ,右侧分别植入 HA、TCP、CHA及脱钙牙基质 (decalcified dentin matrix,DDM)作为对照 ,在 1、3、5及 7周取材作大体观察、组织形态学、扫描电镜观察及生化测定。　结果　各组实验侧及第 4组对照侧植入后 1周软骨形成 ,第 1～ 3组对照侧为纤维结缔组织 ;3周时各组实验侧均有较多的成熟骨组织 ,组织碱性磷酸酶 (alkalinephosphatase,AL P)染色均为阳性。各组对照侧材料被结缔组织包囊 ,AL P染色阴性 ,未见骨组织形成。各组实验侧材料AL P活性及磷 (phosphrus,P)检测水平明显高于相应的对照侧材料 ,实验侧与对照侧比较具有统计学意义 (P<0 .0 5 ) ,而 TCP/ BMP复合材料明显高于另 3种复合材料 ,有统计学意义 (P<0 .0 5 )。5、7周各实验侧及对照     

Bone ingrowth into porous calcium phosphate ceramics: influence of pulsing electromagnetic field

The effect of a pulsing electromagnetic field (PEMF) on bone ingrowth into porous hydroxyapatite (HA) and porous tricalcium phosphate (TCP) implanted in rabbit tibiae was studied. To quantitate the biological response, a recently developed method of surface measurement using a scanning electron microscope was used. The morphometrical findings in the HA pores demonstrated a significantly greater amount of bone and thicker bone trabeculae in the PEMF group as compared with the nonpulsed control group at 3 to 4 weeks postimplantation. No significant differences for these parameters were found in the TCP pores. Histologically, more bone and wider bone trabeculae were observed in the HA implants for the PEMF-treated animals at the early time periods when compared with those of the control animals. Alternatively, the histological findings of the TCP implants were similar between these two groups. These histological results tended to correlate with the morphometrical data. Together, these results suggest that accelerated bone formation and bone maturation occurred in response to PEMF in the HA pores but was without effect in the TCP pores. This stimulatory effect is most significant after 3-4 weeks of PEMF stimulation.     

三种快速成型制作的聚酯/钙磷盐人工骨修复兔桡骨缺损的实验研究

目的检验3种聚酯／钙磷盐植骨材料修复兔桡骨缺损的效果,筛选理想的组织工程用生长因子载体。方法分别采用复合牛骨形态发生蛋白(bBMP)及单纯快速成型工艺制作的3种聚酯／钙磷盐载体材料修复兔桡骨15mm缺损,通过量化评价、影像学、组织学、材料降解及骨密度评价3种聚酯／钙磷盐载体材料修复兔桡骨缺损的效果。结果12周时各材料实验组骨缺损均愈合,各检测指标同对照组比较差异均有统计学意义,空白对照组骨缺损未愈合,以聚乳酸．聚羟基乙酸共聚物／磷酸三钙(PLGA／TCP)材料实验组修复效果最好,聚消旋乳酸／磷酸三钙(PDLLA／TCP)材料实验组次之,最后为聚左旋乳酸／磷酸三钙(PLIA／TCP)材料实验组。结论3种聚酯／钙磷盐材料制作的仿生活性人工骨皆可以修复兔15mm长骨骨缺损,其中以PLGA／TCP材料效果最为理想。     

Bone ingrowth into two porous ceramics with different pore sizes: an experimental study

Many properties of porous calcium phosphate ceramics have been described, but how pore size influences bony integration of various porous ceramics remains unclear. This study was performed to quantify the bony ingrowth and biodegradability of two porous calcium phosphate ceramics with four different pore size ranges (45-80 microm, 80-140 microm, 140-200 microm, and 200-250 microm). Hydroxyapatite (HA) and beta-tricalcium phosphate (TCP) cylinders were implanted into the femoral condyles of rabbits and were left in situ for up to 12 months. The percentage of bone ingrowth and the depth of ingrowth within the pores were determined. Biodegradability of the implants was also evaluated. Bone ingrowth occurred at a higher rate into the TCP than into the HA ceramics with the same pore size ranges. The amount of newly formed bone was statistically smaller (p < 0.05) into ceramics with 45-80 microm pore size than with larger pore size, whatever the implantation time for HA and until four months for TCP. No statistical difference was noted between the three highest pore size ranges. No implant degradation was noted up to four months. Our results suggest that a pore size above 80 microm improves bony ingrowth in both HA and TCP ceramics. Bone formation was higher in the TCP than in the HA implants.     

三种钙磷陶瓷材料复合重组人骨形成蛋白-2体内成骨的研究

目的 探讨和比较3种钙磷陶瓷材料HA、TCP、HA／TCP复合重组入骨形成蛋白。2(rhBMP—2)体内异位成骨效果，为临床应用提供依据。方法 取35只3月龄Wistar大鼠，将复合rhBMP—2的3种钙磷陶瓷材料(1：1)植于鼠背部肌袋内，未复合rhBMP-2的上述3种单纯陶瓷材料为对照组。术后2、4和8周取材，测定植入物碱性磷酸酶(ALP)活性，通过HE染色和计算机图像分析进行组织学和组织计量学观察，比较新生骨组织的形成。结果 术后2、4周复合植入物ALP活性测定从高到低依次为HA、HA／TCP、TCP，但在相同rhBMP—2剂量下，其差异无统计学意义(P＞0．05)，与相对应单纯支架材料比较有统计学意义(P＜0．05)；组织学和组织计量学检测结果显示各复合材料组均有新骨形成，成骨量随时间推移而增加，2周时以HA/rhBMP—2成骨量较多，但3组间差异无统计学意义(P＞0．05)；8周时新骨形成以双相陶瓷HA／TCP最佳，相关参数和图像分析有统计学意义(P＜0．05)，成骨量8周较2、4周多，有统计学意义(P＜0．01)；3种单纯支架材料各观察期均无骨样组织形成。结论 双相陶瓷材料HA／TCP是携带rhBMP—2的钙磷陶瓷良好支架材料。     

Subcutaneous‐induced membranes have no osteoinductive effect on macroporous HA‐TCP in vivo

Induced Membranes Technique was first described to enhance bone reconstruction of large osseous defects. Previous in vitro studies established their osteoinductive potential, due to the presence of opteoblasts precursors and to high amounts of growth factors contained within. The purpose of this study was to test in vivo the osteoinductive properties of induced membranes on a macroporous HA‐TCP in a nonosseous subcutaneous site. Subcutaneous‐induced membranes were obtained in 21 rabbits; 1 month later, the membranes were filled with a biphasic calcium phosphate material composed of 75% hydroxyapatite (HA) and 25% β‐tricalcium phosphate associated or not with autograft. Histological and immunohistochemical studies were performed on membrane biopsies. Undecalcified and decalcified sections were qualitatively and quantitatively analyzed. ⁴⁵Ca uptake was observed and quantified on the sections using microimager analysis. Dense vascularity was found in the induced membranes. New bone formation was detected in the HA‐TCP + autograft samples and increased significantly from 3 to 6 months (p < 0.05). No bone was detected in the biomaterial graft alone in the induced membranes at any time. This study showed that induced membranes placed in a nonosseous site have no osteoinductive properties on a macroporous biphasic calcium phosphate biomaterial. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:155–161, 2009     

Exogenous phytoestrogenic molecule icaritin incorporated into a porous scaffold for enhancing bone defect repair

This study was designed to develop a bioactive scaffold to enhance bone defect repair in steroid‐associated osteonecrosis (SAON). Icaritin, a metabolite of the herb Epimedium, has been identified as an angiogenic and osteogenic phytomolecule. Icaritin was homogenized into poly lactic‐co‐glycolic acid/tricalcium phosphate (PLGA/TCP) to form an icaritin‐releasing porous composite scaffold (PLGA/TCP/icaritin) by fine‐spinning technology. In vitro, high performance liquid chromatography was used to determine the release of icaritin during degradation of PLGA/TCP/icaritin. The osteogenic effects of PLGA/TCP/icaritin were evaluated using rat bone marrow mesenchymal stem cells (BMSCs). In vivo, the osteogenic effect of PLGA/TCP/icaritin was determined within a bone tunnel after core decompression in SAON rabbits and angiography within scaffolds was examined in rabbit muscle pouch model. In vitro study confirmed the sustainable release of icaritin from PLGA/TCP/icaritin with the bioactive scaffold promoting the proliferation and osteoblastic differentiation of rat BMSCs. In vivo study showed that PLGA/TCP/icaritin significantly promoted new bone formation within the bone defect after core decompression in SAON rabbits and enhanced neovascularization in the rabbit muscle pouch experiment. In conclusion, PLGA/TCP/icaritin is an innovative local delivery system that demonstrates sustainable release of osteogenic phytomolecule icaritin enhancing bone repair in an SAON rabbit model. The supplement of scaffold materials with bioactive phytomolecule(s) might improve treatment efficiency in challenging orthopedic conditions. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:164–172, 2012     

An injectable composite material containing bone morphogenetic protein‐2 shortens the period of distraction osteogenesis in vivo

To investigate new methods that can decrease the duration of bone transport (BT) distraction osteogenesis, we injected composite materials containing recombinant human bone morphogenetic protein‐2 (BMP‐2) and induced the generation of a callus bridge by rapid segmental transport (4 mm/day) in a rabbit bone defect model. The composite materials consisted of BMP‐2 (0, 30, or 100 µg), β‐tricalcium phosphate powder (βTCP, 100 mg/animal; particle size, <100 µm), and polyethylene glycol (PEG; 40 mg/animal). A paste of equivalent composition was percutaneously injected at the lengthening and the docking sites after surgery and after BT, respectively. The radiographic, mechanical, and histological examinations 12 weeks post‐operative revealed that the generation of bridging callus in the presence and in the absence of BMP‐2 was significantly different. The callus mass in the bone defect region was adequately and consistently developed in the presence of 100 µg of BMP (administered for 6 weeks), and the bones were consolidated in 12 weeks. Such an adequate callus formation was not observed in the control animals without BMP‐2 treatment. The result of this experimental study suggests the potential application of BMP‐2 in accelerating callus formation and in enabling rapid bone transporting, thereby shortening the treatment period for the repair of diaphyseal bone defects by distraction osteogenesis. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:452–456, 2011     

Collagen-hydroxyapatite/tricalcium phosphate microspheres as a delivery system for recombinant human transforming growth factor-beta 1

The purpose of this study is to evaluate the carrier capability of collagen-hydroxyapatite/tricalcium phosphate (Col-HA/TCP) microspheres to the rhTGF-beta 1 (recombinant human transforming growth factor-beta 1). After anesthesia, a bone defect (7.0 mm in diameter and 10.0 mm in depth) was created at the distal femoral condyles of New Zealand white rabbits. These defects were then completely filled with the implant materials. After 5, 7, 9, 11, 13, and 15 weeks, the animals were sacrificed and histological evaluations were performed. The results showed that when the defects were treated with Col-HA/TCP microspheres without rhTGF-beta 1, there was only spotty new bone formation during the 15 week experimental period and most of the defect was filled with fibrous tissue and inflammatory cells, whereas active bone formation with mature marrow tissue formation was evident in the defect treated with Col-HA/TCP microspheres containing rhTGF-beta 1. Collagen-hydroxyapatite/tricalcium phosphate microspheres were expected to be replaced by the regenerated bone structure as the bone reconstruction and bone-remodeling process occurred. It was apparent that bone regeneration was influenced by the addition of rhTGF-beta 1. Collagen-hydroxyapatite/tricalcium phosphate microspheres were a good carrier for rhTGF-beta 1.     

Effect of Electrical Polarization of Hydroxyapatite Ceramics on New Bone Formation

Large surface charges can be induced on hydroxyapatite (HAp) ceramics by proton transport polarization, but this does not affect β-tricalcium phosphate (TCP) because of its low polarizability. We wished to examine differences in osteogenic cell activity and new bone growth between positively or negatively surface-charged HAp and HAp/TCP plates using a calvarial bone defect model. In the first group of rats, test pieces were placed with their positively charged surfaces face down on the dura mater. In the second group, test pieces were placed with their negatively charged surfaces face down on the dura mater. A third group received noncharged test pieces. Histological examination, including enzymatic staining for osteoblasts and osteoclasts, was carried out. While no bone formation was observed at the pericranium, direct bone formation on the cranial bone debris and new bone growth expanded from the margins of the sites of injury to bridge across both the positively and negatively charged surfaces of HAp and HAp/TCP plates occurred. Electrical polarization of implanted plates, including positive charge, led to enhanced osteoblast activity, though decreased osteoclast activity was seen on the positively charged plate surface. Thus, polarization of HAp ceramics may modulate new bone formation and resorption.     

Promotion of normal healing of bone defects under estrogen deficiency by implantation of beta‐tricalcium phosphate composed of rod‐shaped particles

We compared the healing of bone defects in ovariectomized rats implanted with beta‐tricalcium phosphate (β‐TCP) composed of rod‐shaped particles, which were prepared using the applied hydrothermal method (HTCP), and that of bone defects implanted with conventional β‐TCP composed of globular‐shaped particles (CTCP), which were prepared by normal sintering. Eight‐week‐old female Wistar rats were ovariectomized, and 2 weeks after the operation, 0.5‐ to 0.6‐mm diameter spherical granules of each ceramic were implanted in a bone defect created in the distal end of the femur. Four, 8, and 12 weeks after implantation, the amount of newly formed bone implanted with HTCP was significantly larger than that implanted with CTCP and was equivalent to that in non‐ovariectomized sham‐operated rats. Without implantation, spontaneous repair of the trabecular bone was barely observed. The physiological structure of the trabecular network was maintained in the region implanted with HTCP, but that in the region implanted with CTCP was severely destroyed. Gene expression microarray analysis revealed that the expression of genes involved in interferon signaling pathways was upregulated in osteoclasts cultured on HTCP compared with that cultured on CTCP. Our results suggest that the microstructure of β‐TCP affected the biological behavior of osteoclasts and regulated local bone metabolism. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:189–196, 2014.     

转染Ang-1间充质干细胞加强兔骨缺损修复的实验研究

目的 研究转染血管生成素-l(angiopoiten—1．Ang—1)基因的骨髓间充质干细胞(bone-mesenchvmal stem cells，BMSCs)对免骨缺损的修复作用。方法以脂质体介导pCDNA3．Ang—1质粒转染体外分离培养的兔BMSCs，与TCP陶瓷复合，修复兔桡骨15mm长节段性骨缺损?以未转染细胞作对照，进行电镜、组织学及核素扫描等方法检测骨修复情况。结果细胞与TCP材料复合后生长良好。组织学检查见转染细胞组毛细血管生长及新骨形成活跃，核素扫描见实验组局部血供丰富、代谢旺盛。结论Ang—l转染细胞组血供增加和骨修复加速，与细胞因子局部定向释放，加强血管形成及骨代谢有关。Ang—1修饰的BMSCs预构人工骨有助于加速骨缺损的修复?     

Comparative study of porous hydroxyapatite and tricalcium phosphate as bone substitute

This study was performed to quantitate the bone ingrowth and biodegradability of porous calcium phosphate. Two kinds of coralline hydroxyapatite (CHA), along with sintered tricalcium phosphate (TCP), were evaluated. All implants had totally interconnecting pores. These pores measured 260-600 mu for CHA-Goniopora (CHAG), 190-230 microns for CHA-Porites (CHAP), and 100-300 microns for TCP. Cylindrical implants (3 mm in diameter by 8 mm in length) were implanted into the diaphyses of rabbit tibias for 3 to 24 weeks. The quantity of regenerated bone, remaining implant, nonmineralized space, and the middle two quarters of the cortical area were measured by a computerized operator-assisted analysis for bone histomorphometry. At 3 weeks after implantation, 17.3% of CHAG, 11.3% of CHAP, and 7.0% of TCP were infiltrated by regenerated bone. At 24 weeks, 56.1% of CHAG, 52.7% of CHAP, and 44.7% of TCP were occupied by lamellar-type bone. Implant degradation was noted to be 46.4% for TCP and 27.5% for CHAP. In contrast, CHAG did not show appreciable degradation until 24 weeks.     

Bone ingrowth into three different porous ceramics implanted into the tibia of rats and rabbits

Three different porous ceramics--calcium aluminate, calcium hydroxyapatite, and tricalcium phosphate--were implanted into the proximal tibia in rats and rabbits to study the interactions between these ceramics and a bony site that is abundant in bone marrow. New bone was consistently formed within the bone marrow surrounding and adjacent to all three types of ceramics. Calcium hydroxyapatite and tricalcium phosphate ceramics permitted bone ingrowth into their pores. The newly formed bone was found only in the part of the ceramic intruding into the bone, not in the portion protruding in the soft tissues outside the tibia. Partial replacement of the new bone opposite the medullary portion by new hemopoietic marrow occurred with longer implantation times. In contrast, no bone was seen within the pores of any of the calcium aluminate implants.     

Repair of bone defects with marrow cells and porous ceramic. Experiments in rats

We studied the role of bone-marrow reconstituted porous ceramics in enhancing healing of a 5-mm femoral diaphyseal defect fixed with a rigid polyethylene plate in rats. Osseous repair was evaluated by histologic scoring. When blocks of porous calcium phosphate ceramics alone were introduced into the defects, most cases showed fibrous tissue interposition at the host bone-ceramic junction 1 month after implantation, and only four of 12 defects developed osseous or osteochondral union at both the proximal and distal junctions 2 months after surgery. However, when the ceramic was combined with syngeneic viable marrow cells, new bone formation occurred in isolated pore regions of the ceramic at 1 month, and extensive bone formation was seen in most pore regions 2 months after implantation. Out of 12 implants, complete bone union was seen in eight, and one showed osseous or osteochondral union at both junctions 2 months after surgery. Our results indicated that composite grafts of porous calcium phosphate ceramics and marrow cells may be clinically applicable to enhance osteogenesis and osteoconduction.