Effects of recombinant human fibroblast growth factor-2 on osteogenic cell populations during orthopic osteogenesis in vivo

The osteogenic effects of fibroblast growth factor-2 (FGF-2) in vivo on different cell populations of the osteoblastic cell lineage have not been fully elucidated. In this study, the efficacy of recombinant human fibroblast growth factor-2 (rhFGF-2) to stimulate orthopic bone formation in transosseous rat mandibular defects, with different cell populations allowed access to the defects, was investigated with the aim to further decipher FGF-2 effects. Three different doses of rhFGF-2 (10 ng, 100 ng, and 1 microg) were delivered in an absorbable collagen sponge carrier, whereas some defects were implanted with the carrier only, and some were left untreated. Barrier membranes, made of microporous expanded polytetrafluoroethylene, were simultaneously placed over half the number of defects in each treatment group, thus forcing osteogenic cells to be derived from intraosseous sources. Evaluation was made by light microscopy and computerized image analysis after 12 and 24 of days healing. Whereas no general stimulatory effect could be ascertained at 12 days, higher rhFGF-2 doses decreased bone formation by both intraosseously and periosteally derived cells. At 24 days, a clear, although rather limited, stimulatory effect on osteogenesis was observed, but again a decrease was observed with the 1 microg dose. At both observation periods, an increased number of osteocytes was found in the newly formed bone at sites treated with the lower rhFGF-2 doses, whereas the high-dose rhFGF-2 resulted in a return to control levels, irrespective of whether cells were intraosseously derived or from the periosteum also. Based on differential analysis of bone healing by cells from different sources as well as on bone cellularity, the results suggest that rhFGF-2 in vivo exerts a stimulatory effect on proliferation of committed osteoblastic cells. This effect is biphasic, in that higher doses are without effect or may even be inhibitory. No inductive effect on osteoblast recruitment could be found. These effects differ from those of, for instance, BMP-2 and TGF-beta1.     

Human maxillary tuberosity and jaw periosteum as sources of osteoprogenitor cells for tissue engineering.

OBJECTIVE: Bone tissue engineering is a promising approach for bone reconstruction in oral-maxillofacial surgery. This study investigates the suitability of oral skeletal tissues as convenient and accessible sources of osteogenic progenitors as an alternative to the iliac crest bone marrow. STUDY DESIGN: Samples of maxilla tuberosity (MT) and maxillary and mandibular periosteum (MP) were obtained during routine oral surgery, and donor site morbidity was assessed using a "split-mouth" approach. Cells isolated from MT (bone marrow stromal cells; MT-BMSCs) and from MP (periosteal cells; M-PCs), were analyzed for clonogenicity, phenotype, expression of osteogenic markers, and ability to form bone in vivo. RESULTS: Both MT-BMSCs and M-PCs included clonogenic cells, showed comparable phenotypic profiles, and expressed early osteogenic markers. Most importantly, both cell populations formed bone upon ectopic in vivo transplantation. CONCLUSION: MT-BMSCs and M-PCs behaved as osteoprogenitor cells in vitro and in vivo. MT and MP may be considered as suitable sources of cells for bone tissue engineering in humans.     

Osteogenic potential of primed periosteum graft in the rat calvarial model

Repair of bone defects remains a major concern in plastic and maxillofacial surgery. Based on modern concepts of tissue engineering, periosteum has gained attention as a suitable osteogenic material. We tested the hypothesis that surgically released and immediately repositioned periosteum would exhibit high osteogenic capacity upon grafting in a rat calvarial defect. Seven days after periosteum was released from the tibia and immediately repositioned, the "primed periosteum graft" (PPG; n = 15) was placed into a critical-sized defect of rat calvaria and the process of bone formation was evaluated histologically, immunohistologically, and radiographically at 7, 14, and 21 days after grafting. Findings were compared with a nonprimed periosteal graft (NPG; n = 15).Endochondral ossification was observed in both the PPG and NPG. The PPG showed higher expression of proliferative cell nuclear antigen, bone morphogenetic protein, and vascular endothelial growth factor than the NPG. Three-dimensional radiographic examination revealed significantly increased bone formation in the PPG than in the NPG (P < 0.01). These findings suggested that surgical stimulation of the periosteum enhanced the osteogenic potential of periosteal cells. This method may be suitable for the clinical repair of bone defects.     

Filling the bone defect with osteogenic material

In this experimental study with bone defects, we focussed on the one hand on external and internal osteogenic callus formation after filling the defect and on the other on the osteochondrogenic differentiation capacity of 4-day-old fibrous-like callus grafts and 12-day-old woven bone grafts in an osteogenic environment. A standard cortical bone defect of the femur was created in 95 young rats. The defect was filled with a cortical bone graft and 4- and 12-day-old callus grafts. The grafts were transplanted as such or in Nucleopore chambers. Follow-up was done at 1, 2, 3 and 6 weeks. The osteochondrogenic tissue formed was studied histologically and histomorphometrically. The results suggest that the filling of the bone defect had no influence on the primary external and internal osteogenic callus formation at 1 and 2 weeks. At 3 and 6 weeks in the chamber groups the persisting internal bridging woven bone was converted into more compact lamellar bone whereas periosteal callus remained at the edges of the defect. In the other groups at 3 and 6 weeks the normal shape of the cortex was reconstituting. Four-day-old fibrous-like callus formed bone in the Nucleopore chamber, indicating that fibrous-like callus tissue at 4 days contains osteogenic cells. Twelve-day-old callus consisting of woven bone was partially differentiated to cartilage, showing that woven bone contains cells capable of chondrogenic differentiation.     

Critical size defect in the canine mandible.

OBJECTIVE: The purpose of this study was to determine the minimum size defect in a canine mandible that would not spontaneously heal during the dog's natural life (the critical size defect). STUDY DESIGN: Sixteen adult female mongrel dogs underwent continuity resection on both sides of the mandible to create bilateral defects. In 8 dogs, mandibular defects ranging from 5 to 20 mm were created with periosteal resection. In the other 8 dogs, mandibular defects ranging from 30 to 60 mm were created preserving the periosteum. The dogs were then killed at 6 months and the defects examined using radiographs and histologic analysis. RESULTS: When the periosteum was removed, mandibular defects greater than 15 mm failed to heal across the entire defect. However, when the periosteum was preserved, mandibular defects needed to be greater than 50 mm in order to fail to heal. CONCLUSION: The critical size defect in a canine mandible model is 15 mm when the periosteum is removed and 50 mm when the periosteum is preserved.     

Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2)

BACKGROUND: Damaged articular cartilage has a limited ability to repair. Operative removal of damaged cartilage and penetration into the subchondral bone to allow population of the defect with progenitor cells can result in filling of the defect with repair tissue. However, this repair tissue often degenerates over time because of its inability to withstand the mechanical forces to which it is subjected. We previously reported that recombinant human bone morphogenetic protein-2 (rhBMP-2) improves the repair of full-thickness defects of cartilage as long as six months postoperatively. We have now extended that study to examine the quality of the repair tissue at one year. METHODS: Full-thickness defects of cartilage were created in the trochlear groove of twenty-five adult New Zealand White rabbits. Eight defects were left empty, eight were filled with a collagen sponge, and nine were filled with a collagen sponge impregnated with five micrograms of rhBMP-2. The animals were killed at fifty-two weeks postoperatively, and the gross appearance of the healed defect was assessed. The repair tissue was examined histologically and was evaluated, according to a grading scale, by four individuals who were blinded with respect to the treatment. The tissue sections were immunostained with antibodies against type-I collagen, type-II collagen, aggrecan, and link protein. The residence time of the rhBMP-2 in the cartilage defect was evaluated in vivo with use of scintigraphic imaging of radiolabeled protein. RESULTS: One year after a single implantation of a collagen sponge containing five micrograms of rhBMP-2, the defects had a significantly better histological appearance than the untreated defects (those left empty or filled with a collagen sponge). The histological features that showed improvement were integration at the margin, cellular morphology, architecture within the defect, and reformation of the tidemark. The total scores were also better for the defects treated with rhBMP-2 than for the untreated defects, but in no instance was the repair tissue identical to normal articular cartilage. The thickness of the cartilage in the defects treated with rhBMP-2 was 70 percent that of the normal cartilage, an observation that was identical to that at twenty-four weeks postoperatively. Immunostaining demonstrated significantly less type-I collagen in the defects treated with rhBMP-2 than in the untreated defects. Immunostaining for other matrix components showed no difference among the treatment groups. The mean residence time of rhBMP-2 in the cartilage defects was eight days with an elimination half-life of 5.6 days. Detectable amounts of rhBMP-2 were present as long as fourteen days after implantation. CONCLUSIONS: The problems associated with operative repair of cartilage include the formation of fibrocartilage rather than normal articular cartilage and the degeneration of that repair tissue over time. Our results demonstrate that the addition of rhBMP-2 to the operative site after creation of a full-thickness defect results in an improvement in the histological appearance and composition of the extracellular matrix at one year postoperatively. If these experimental results translate directly to the clinical situation, it is possible that the addition of rhBMP-2 to existing operative treatments for the repair of cartilage may improve the repair process and may help to maintain the integrity of the repair tissue.     

自体骨髓基质干细胞复合珊瑚修复犬下颌骨节段缺损的初步研究

目的应用自体骨髓基质干细胞(bonemarrowstromalcells,BMSCs)复合珊瑚构建组织工程化骨,修复犬下颌骨节段性缺损。方法体外扩增培养、成骨诱导犬BMSCs。将第二代细胞复合珊瑚后修复犬自体右侧3cm的下颌骨节段缺损(n=6);以单纯珊瑚植入缺损处为对照(n=6),术后12、32周分别通过影像学,大体形态观察,组织学和生物力学的方法检测骨缺损的修复效果。结果成骨诱导的BMSCs在珊瑚支架上生长良好。X线片显示12周时实验组骨痂较多,对照组材料明显吸收;32周时CT、X线片和大体观察显示术后实验组骨愈合良好,对照组为骨不连;骨密度检测示实验组显著高于对照组(P<0.05);组织学示实验组有较多成熟骨呈骨性愈合,对照组为纤维性愈合;生物力学测试实验组与正常下颌骨力学强度差异无统计学意义(P>0.05)。结论自体成骨诱导BMSCs复合珊瑚形成的组织工程化骨可修复犬下颌骨节段缺损。     

Direct percutaneous gene delivery to enhance healing of segmental bone defects

BACKGROUND: Healing of segmental bone defects can be induced experimentally with genetically modified osteoprogenitor cells, an ex vivo strategy that requires two operative interventions and substantial cost. Direct transfer of osteogenic genes offers an alternative, clinically expeditious, cost-effective approach. We evaluated its potential in a well-established, critical-size, rat femoral defect model. METHODS: A critical-size defect was created in the right femur of forty-eight skeletally mature Sprague-Dawley rats. After twenty-four hours, each defect received a single, intralesional, percutaneous injection of adenovirus carrying bone morphogenetic protein-2 (Ad.BMP-2) or luciferase cDNA (Ad.luc) or it remained untreated. Healing was monitored with weekly radiographs. At eight weeks, the rats were killed and the femora were evaluated with dual-energy x-ray absorptiometry, micro-computed tomography, histological analysis, histomorphometry, and torsional mechanical testing. RESULTS: Radiographically, 75% of the Ad.BMP-2-treated femora showed osseous union. Bone mineral content was similar between the Ad.BMP-2-treated femora (0.045 +/- 0.020 g) and the contralateral, intact femora (0.047 +/- 0.003 g). Histologically, 50% of the Ad.BMP-2-treated defects were bridged by lamellar, trabecular bone; the other 50% contained islands of cartilage. The control (Ad.luc-treated) defects were filled with fibrous tissue. Histomorphometry demonstrated a large difference in osteogenesis between the Ad.BMP-2 group (mean bone area, 3.25 +/- 0.67 mm(2)) and the controls (mean bone area, 0.65 +/- 0.67 mm(2)). By eight weeks, the Ad.BMP-2-treated femora had approximately one-fourth of the strength (mean, 0.07 +/- 0.04 Nm) and stiffness (mean, 0.5 +/- 0.4 Nm/rad) of the contralateral femora (0.3 +/- 0.08 Nm and 2.0 +/- 0.5 Nm/rad, respectively). CONCLUSIONS: A single, percutaneous, intralesional injection of Ad.BMP-2 induces healing of critical-size femoral bone defects in rats within eight weeks. At this time, the repair tissue is predominantly trabecular bone, has normal bone mineral content, and has gained mechanical strength.     

Expression of endogenous BMP-2 in periosteal progenitor cells is essential for bone healing

Bone morphogenic protein 2 (BMP-2) plays a key role in skeletal development, repair and regeneration. To gain a better understanding of the role of BMP-2 in periosteum-mediated bone repair, we deleted BMP-2 postnatally at the initiation stage of healing utilizing a Tamoxifen-inducible CreER mouse model. To mark the mutant cells, we further generated a BMP-2(f/f); CreER; RosaR mouse model that enabled the activation of a LacZ reporter gene upon treatment of Tamoxifen. We demonstrated that deletion of BMP-2 at the onset of healing abolished periosteum-mediated bone/cartilage callus formation. In a chimeric periosteal callus with cells derived from both wild type and the mutant, over 90% of the mutant mesenchymal progenitors remained undifferentiated. Within differentiated bone and cartilage tissues, only a few cells could be identified as mutants. Using a bone graft transplantation approach, we further showed that transplantation of a mutant bone graft into a wild type host failed to rescue the deficient differentiation of the mutant cells at day 10 post-grafting. These data strongly suggest that the endogenous expression of BMP-2 plays a critical role in osteogenic and chondrogenic differentiation of periosteal progenitors during repair. To determine whether BMP-2 deficient cells remained responsive to exogenous BMP-2, we isolated periosteal mesenchymal progenitors from BMP-2 deficient bone autografts. The isolated cells demonstrated a 90% reduction of endogenous BMP-2 expression, accompanied by significant decrease in cellular proliferation and a near blockade of osteogenic differentiation. The addition of exogenous BMP-2 partially rescued impaired proliferation and further enhanced osteogenic differentiation in a dose dependent manner. Taken together, our data show that the initiation of the cortical bone repair in vivo is controlled by endogenous BMP-2. Future studies are necessary to determine the mechanisms by which the BMP-2 pathway is activated in periosteal progenitor cells at the onset of cortical bone repair.     

以自体诱导和无诱导的骨髓基质干细胞复合珊瑚修复犬下颌骨节段缺损的比较研究

目的分别采用诱导和无诱导的自体骨髓基质干细胞（Bone marrow stromal cells，BMSCs）复合珊瑚构建组织工程化骨，修复犬下颌骨节段性缺损，比较修复效果。方法体外扩增、成骨诱导或无诱导培养犬BMSCs，分别将第2代细胞复合珊瑚后修复犬自体右侧3cm的下颌骨节段缺损（诱导组n=6，无诱导组n=6）。术后32周，分别通过Micro-CT、大体形态观察和组织学方法检测骨缺损的修复效果。结果32周时，Micro-CT检测示诱导组骨容积率和密度均显著高于对照组（P〈0.05）；大体观察示诱导组骨愈合良好，无诱导组中的3条犬为骨不连；组织学检测诱导组有较多成熟骨形成，缺损部分均呈骨性愈合。无诱导组中的3只犬有新骨形成，但形态不完整，另3只犬的缺损部分呈纤维性愈合。结论成骨诱导的自体BMSCs复合珊瑚形成的组织工程化骨修复犬下颌骨节段缺损效果优于无诱导组。     

自体骨膜细胞复合胶原涂层煅烧骨修复骨缺损的实验研究

目的：观察骨膜成骨细胞（periosteal-derived osteoblast.POB)与胶原涂层煅烧骨（true bone ceramic collage,TBCc)移植的成骨性能，探讨治疗骨缺损的新方法。方法：选牛松质骨制备胶原涂层煅烧骨载体。用兔骨膜成骨细胞与TBCc复合并自体移植到15mm骨缺损模型，移植后4、8、12、16周取材，行组织学、X线拍片和X射线能谱分析，计算机图像分析新生骨面积。结果：复合细胞的TBCc组骨生成、新骨面积和骨连接情况明显优于单纯TBCc组。结论：自体骨膜细胞复合煅烧骨具有较强的促进骨修复作用。     

Extraosseous bone formation obtained by association of mesenchymal stem cells with a periosteal flap in the rat

BACKGROUND: Local bone cell therapy consists in grafting a large number of osteocompetent cells in the bone defect. Mesenchymal stem cells (MSC) have been demonstrated as an attractive cell source for tissue-engineering applications because of their ability to be easily isolated and expanded from adult bone marrow and their versatility for pluripotent differentiation into mesenchymal tissues. METHODS: The purpose of our work was to evaluate in vitro the osteogenic potential (proliferation and differentiation) of rat MSC cultured in monolayer conditions and encapsulated in alginate beads and in vivo the osteogenic potential of encapsulated MSC implanted at an extraosseous site associated with a periosteal flap to obtain the equivalent of a vascularized bone autograft. RESULTS: In vitro, the encapsulation of MSC in alginate beads maintains their degree of differentiation towards the osteoblastic lineage. In vivo, standard radiographs revealed "calcifications" adjacent to the area where alginate beads had been implanted in both groups (in the presence or the absence of MSC). In the group "beads alone," histologic analysis showed that calcifications reflected only a peripheral calcification with no bone formation. On the contrary, in the group "beads + MSC," a large mineralization process took place characterized by lamellar mature bone with osteocytes after 10 weeks.     

Heterotopic neo-osteogenesis from vascularized periosteum and bone grafts

BACKGROUND: Periosteum is an osteogenic, flexible tissue. This study investigated the osteogenic potential of vascularized periosteal flaps in heterotopic conditions and compared it to the neo-osteogenesis from vascularized periosteal flaps combined with bone grafts with different properties (autologous and xenograft). METHODS: Vascularized periosteal flaps from the hindlimbs of 48 rabbits formed cylindrical pouches that were buried in muscles. The pouches were filled with autologous bone grafts (P/A group, n = 16), xenograft (P/X group, n = 16), or left empty (P/E group, n = 16). Specimens were harvested between 1 and 4 months and underwent radiographic, histologic, and histomorphometric evaluation. RESULTS: The total surface area was larger in the groups combined with bone grafts. Osseous apposition did not differ significantly in the P/A and P/X groups (p > 0.05). The central cavity contained hematopoietic cells (P/A), xenograft (P/X), or was absent (P/E). CONCLUSION: Vascularized periosteal flaps presented strong osteogenic capacity in heterotopic conditions. Combination with bone grafts resulted in larger specimens. The quality of neo-osteogenesis was not influenced by the different properties of combined bone grafts.     

Bone regeneration in the rat mandible with bone morphogenetic protein-2: a comparison of two carriers.

OBJECTIVE: To compare mandibular bone regeneration with bone morphogenetic protein-2 (BMP-2) delivered with two carriers: a hyaluronic acid polymer (HY), and a collagen carrier complexed with calcium hydroxyapatite and tricalcium phosphate (collagen/HA/TCP). STUDY DESIGN: Defects were created in the bilateral mandibular bodies of 16 Sprague-Dawley rats. The defects were filled with the HY carrier, the HY carrier loaded with BMP-2, the collagen/HA/TCP carrier, or the collagen/HA/TCP carrier loaded with BMP-2. Animals were euthanatized after 6 weeks, and the hemi-mandibles were analyzed histomorphologically. RESULTS: Specimens containing BMP-2 had significantly larger new bone and marrow volumes than control specimens. Specimens in the hyaluronan/BMP-2 group tended to have larger volumes of new bone and osteoid than collagen/HA/TCP/BMP-2 specimens, though these differences were not statistically significant. CONCLUSION: The HY and collagen/HA/TCP carriers had comparable efficacy for bone healing with BMP-2. SIGNIFICANCE: Bone morphogenetic proteins can be delivered with commercially available alloplasts as osteogenic bone substitutes for the repair of craniofacial bone defects. EBM rating: B-2.     

Comparison of Osteogenic Potentials of BMP4 Transduced Stem Cells from Autologous Bone Marrow and Fat Tissue in a Rabbit Model of Calvarial Defects

We compared bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs) of adult rabbits under identical conditions in terms of their culture characteristics, proliferation capacity, osteogenic differentiation potentials induced by adenovirus-containing bone morphogenetic protein 4 (Ad-BMP4) in vitro, and capacity to repair calvarial defects in the rabbit model by autologous transplantation ex vivo. According to the results of growth curve, cell cycle, and telomerase activity analysis, ADSCs possess a higher proliferation potential. Both of the Ad-BMP4 transduced MSCs expressed BMP4 mRNA and protein and underwent osteogenic differentiation. Up-regulated mRNA expression of all osteogenic genes was observed in differentiated BMSCs and ADSCs, but with different patterns confirmed by real-time RT-PCR. Deposition of calcified extracellular matrix was significantly greater in differentiated ADSCs compared with differentiated BMSCs. X-ray and histological examination indicated significant bone regeneration in the calvarial defects transplanted with Ad-BMP4 transduced autologous MSCs compared to the control groups. There was no significant difference in new bone formation in Ad-BMP4 transduced MSCs based on quantitative digital analysis of histological sections. The use of ADSCs often resulted in the growth of fat tissue structures in the control groups, and the fat tissue structures were not seen with BMSC cells. Our data demonstrate that BMP4 can be potently osteoinductive in vivo, resulting in bone repair. ADSCs may be an attractive alternative to BMSCs for bone tissue engineering under appropriate stimuli. But the easy adipogenic differentiation needs to be considered when choosing adipose tissue for specific clinical application.     

Observations on healing following endodontic surgery in nonhuman primates (Macaca fascicularis): effects of rhBMP-2.

OBJECTIVES: The potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) to enhance bone healing following endodontic surgery was tested. The pattern and timing of de novo bone formation and cementum regeneration, and the potential for root resorption and ankylosis to accompany bone formation were evaluated. STUDY DESIGN: Pulpal infections were induced in maxillary and mandibular incisor teeth in young adult Cynomolgus monkeys. The teeth received conventional endodontic treatment immediately followed by surgical root resection. In a randomized split-mouth design, contralateral apical bone defects received rhBMP-2 in absorbable collagen sponge (ACS) carrier or served as sham-surgery controls to provide histological and radiographic evaluations following 1 (mandibular incisors) and 4.5 (maxillary incisors) month(s) postsurgery. RESULTS: At 1 month postsurgery trabecular bone filled the apical bone defects. The newly formed bone appeared considerably more mature and had assumed characteristics of the contiguous resident bone at 4.5 months postsurgery. The resected root tips were almost completely covered by new cementum with a maturing functionally oriented periodontal ligament. Localized inflammatory infiltrates were associated with the filled root canals and extruded root-filling material. Root resorption and ankylosis were not observed. There were no apparent differences in healing patterns between sites implanted with rhBMP-2/ACS and those serving as sham-surgery controls. CONCLUSIONS: Under conditions where the influence of infectious elements and irritation caused by root filling material are minimized, bone formation and cementum regeneration appears rapid following endodontic surgery. rhBMP-2/ACS did not offer an obvious benefit above and beyond that of the native osteogenic potential in this animal model.     

A biodegradable delivery system for antibiotics and recombinant human bone morphogenetic protein-2: A potential treatment for infected bone defects.

To produce an osteogenic and bacteriocidal biomaterial for the treatment of infected nonunions or bone defects, a synthetic degradable block copolymer of poly-D,L-lactic acid segments with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) segments was mixed with recombinant human BMP-2 (rhBMP-2) and antibiotics at high concentration. We then examined the in vitro elution profile of an antibiotic (teicoplanin) from the polymer, the effects of antibiotics on the bone-inducing capacity of rhBMP-2 or on ectopic new bone formation induced by the rhBMP, and the ability of the polymer to repair bone in a rat cranial defect model. Approximately 40% of teicoplanin was released within the first 24 h, with the remaining amount released steadily over 21 days with no loss of antibacterial activity. The polymer had disappeared by degradation in the phosphate buffered saline (pH 7.4) at the end of the incubation period. The in vivo performance of pellets with antibiotics and rhBMP-2 revealed no significant change in bone yield within the ossicles after 3 weeks. Also, antibiotics had no inhibitory effect on the ability of rhBMP2 to repair cranial defects. Indeed, when the defect was filled by a polymer disc loaded with rhBMP-2 with or without teicoplanin, the defect was repaired by new bone, and normal anatomy was restored within 6 weeks. In conclusion, the PLA/DX/PEG polymer appears to work as effectively for antibiotics as it does for rhBMP-2. Additionally, the biological activity of rhBMP-2 was retained irrespective of the presence of antibiotics.     

Cellular origin and evolution of neochondrogenesis in major full-thickness defects of a joint surface treated by free autogenous periosteal grafts and subjected to continuous passive motion in rabbits

A graft of periosteum from the tibia of 27 rabbits was incubated in vitro with tritiated thymidine for 24 hours and then transplanted into a full-thickness defect in the patellar groove. The rabbits were managed after the operation on continuous passive motion (CPM), and the joints excised at intervals of two to 21 days. After one week the cells had begun to synthesize glycosaminoglycan and by two weeks the tissue resembled immature hyaline cartilage. Thymidine-labeled cells were seen throughout the entire regenerated tissue. The cellular origin of the hyaline-like tissue that filled the defects was the progenitor cells of the periosteal graft.     

Osteogenesis from periosteal autografts in ulnar defects in dogs

The quantity of new bone formed by revascularized periosteal grafts was compared with that formed by nonvascularized periosteal grafts in ulnar diaphyseal defects in dogs. Although in general the revascularized periosteal grafts produced a greater quantity of bone than their nonvascularized counterparts, this osteogenic behavior was not consistent. The results, however, are sufficiently encouraging to merit further investigation into the free transfer of revascularized periosteal autografts.