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Objectives: The objective of this study was to determine the role and reliability of the free medial femoral condyle (MFC) flap (MFCF) in demanding foot and ankle reconstruction procedures., Materials and Methods: A search of the MEDLINE, PubMed, and Embase electronic databases was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines between January 2008 and September 2023. Articles concerning free MFC bone flaps for reconstruction of the foot and ankle regions were included. Outcomes of interest included flap failure, complications, union rate, time to union, and functional scores., Results: Twenty studies involving 131 patients met the inclusion criteria. The most common clinical indications for the free MFCF were nonunion, avascular necrosis, and osteomyelitis. The most common sites of nonunion were tibiotalar arthrodesis (50%) and subtalar arthrodesis (33%). Overall, the bony union rate was 93.1%, with a mean time to union of 14.6±0.1 weeks. There were no flap failures reported. Postoperative complications were observed in 39 (29.7%) cases (e.g., delayed donor site wound healing, flap debulking, medial condyle osteonecrosis, and donor site numbness), with 21 (16%) patients requiring further operative intervention. No major donor or recipient site morbidity occurred, except for one case., Conclusion: Free MFCFs offer a versatile and dependable choice for cases of foot and ankle reconstruction, displaying favorable rates of bone fusion and acceptable complication rates. Existing literature indicates that MFC reconstruction in the foot and ankle is not associated with significant morbidity at the donor or recipient sites. The pooled data demonstrated a 93% success rate in achieving bone fusion in the foot and ankle region, supporting the view that it can be considered another option of treatment.

Purpose: To characterize the periosteal and endosteal arterial perfusion of the proximal phalanx using micro-computed tomography angiography (micro-CTA)., Methods: Cadaveric upper extremities were injected with a barium sulfate/gelatin suspension. Phalanges were imaged using micro-CTA and analyzed with a focus on osseous arterial anatomy. Periosteal and endosteal perfusion was characterized by number of vessels, length, anatomic course, and caliber., Results: The base of the proximal phalanx had a significantly greater number (8.0 ± 3.5) of periosteal vessels than those of the shaft (4.1 ± 1.6) and head (1.3 ± 1.1). One-third (34.4%) of the specimens demonstrated a complete absence of periosteal vessels in the head. A nutrient endosteal vessel was noted in 100% of the specimens. Entering at the junction of the middle and distal third of the bone (25.8 ± 3.9 mm from base), the nutrient vessel entered the proximal phalanx of the index finger along its ulnar aspect (8 of 8 specimens), the middle finger along its radial aspect (6 of 8), the ring finger along its ulnar aspect (5 of 8), and the little finger along its radial aspect (7 of 8). The nutrient vessel branched into proximal and distal extensions toward the shaft and head, respectively, with an average endosteal length of 10.7 ± 5.2 mm and average diameter of 0.36 ± 0.11 mm., Conclusions: Periosteal contributions to the perfusion of the proximal phalanx appear to diminish distally. The endosteal arterial anatomy remains consistent, with a single nutrient vessel entering the intramedullary canal with reliable laterality on each digit. This is often the only vessel supplying the head of the proximal phalanx, making this area particularly susceptible to vascular compromise., Clinical Relevance: An understanding of the patterns of perfusion of the proximal phalanx provides some insight into clinically observed pathology, as well as guidance for operative management., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Periosteum is a highly vascularized membrane lining the surface of bones. It plays essential roles in bone repair following injury and reconstruction following invasive surgeries. To broaden the use of periosteum, including for augmenting in vitro bone engineering and/or in vivo bone repair, we have developed an ex vivo perfusion bioreactor system to maintain the cellular viability and metabolism of surgically resected periosteal flaps. Each specimen was placed in a 3D printed bioreactor connected to a peristaltic pump designed for the optimal flow rates of tissue perfusate. Nutrients and oxygen were perfused via the periosteal arteries to mimic physiological conditions. Biochemical assays and histological staining indicate component cell viability after perfusion for almost 4 weeks. Our work provides the proof-of-concept of ex vivo periosteum perfusion for long-term tissue preservation, paving the way for innovative bone engineering approaches that use autotransplanted periosteum to enhance in vivo bone repair.

Reconstruction of the cervical spine using free vascularized bone flaps has been described in the literature. The reports involve either one level or, when multiple levels, they describe en bloc resection and reconstruction. Stabilization of different levels with a preserved intermediate segment with a single vascularized flap has not been described. We report on the case of a 55-year-old man, who had been operated several times using conventional techniques for cervical myelopathy and instability, who presented to us with severe neck pain. Diagnostic procedures showed pseudarthrosis of C3/4 and stress-overload of the C3/4 and C5/6 segments. The C4/5 fusion was adequately rigid, but avascular. We performed anterior cervical fusion at the C3/4 and C5/6 levels with a vascularized fibula flap modified as a double island. The rigidly fused C4/5 block was preserved and vascularized with the periosteum bridging the two fibular islands. The method and technique are described in detail. Fusion was adequate. Donor site morbidity was minimal and temporary. The patient is symptom free to date (25 months). The suggested method provides the possibility of vertebral fusion at different levels using a single vascularized flap. The indications for this procedure are (1) repeated failure of conventional methods, (2) established poor bone healing and bone non-union with avascular grafts and (3) a well-fused or preserved intermediate segment. The relevant literature is reviewed. [ABSTRACT FROM AUTHOR]

A recent article published in Nature Metabolism, "A network of trans-cortical capillaries as a mainstay for blood circulation in long bones," explained the long bone vascularity. In the mouse model, the authors demonstrated hundreds of transcortical vessels (TCVs) commencing from the bone marrow and traversing the whole cortical thickness. They realized that TCVs were the same as bleeding vessels of periosteal bed observed in the human tibia and femoral epiphysis during surgery. TCVs expressed arterial or venous markers and were proposed to be the backbone of bone vascularity as 80% of arterial and 59% of venous blood distributed through them. This new evidence challenged the existence of the "cortical capillaries" stated in previous literature. We conducted a review of the existing literature to compare this model with those in earlier research. The bone vascularity model was explained by many researchers who did their work in animal models like pig, dog, rabbit, and mouse. The TCVs were identified in these animal model studies as cortical capillaries or vessels of cortical canals. Studies are scarce, showing the presence of TCVs in humans. The role of TCVs in human cortical vascularity remains ambiguous until the substantial evidence is collected in future studies., (© 2020 American Association for Anatomy.)

Purpose: To evaluate clinical and radiological outcomes after surgical treatment of scaphoid nonunion in adolescents with a vascularized thumb metacarpal periosteal pedicled flap (VTMPF)., Methods: Twelve patients younger than 18 years with scaphoid nonunion, who underwent a VTMPF procedure without bone grafting, were included for this prospective cohort study, at a mean follow-up of 10.2 months. Patients were operated on by 3 different hand surgeons at 3 hand surgery institutions. All patients received a VTMPF, but with different scaphoid internal fixation modalities, in 10 cases using 1 or 2 retrograde 2-mm headless compression screws and in 2 cases without internal fixation., Results: In 11 boys and 1 girl, the mean age was 15.6 years. There were 1 type D1 nonunions (Herbert classification), 6 type D2, 2 type D3, and 2 type D4. Six patients had previously undergone an unsuccessful surgical attempt to treat their nonunion. The mean anterior bone defect was 3.5 mm in length. The patients experienced no postoperative complications. Successful consolidation was achieved in all cases, with 79% cross-sectional trabecular bridging at 12 weeks. Pain subsided after surgery and patients experienced improvements in both their Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Modified Mayo Wrist Score (MMWS) results. Overall, 34% and 40% gains in strength and wrist motion, relative to the contralateral normal side, were observed., Conclusions: In this study, the use of VTMPF for scaphoid nonunion in children and adolescents is associated with generally good outcomes., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2019 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Nitrogen-containing bisphosphonates (BIS) are potent therapeutics in osteoporosis, but their use may result in osteonecrotic side-effects in the maxillofacial region. Periosteal microcirculatory reactions may contribute to the development of bone-healing complications, particularly in osteoporotic bones, where ischemia-reperfusion (IR) events often develop during orthopaedic/trauma interventions. The effect of BIS on the inflammatory reactions of appendicular long bones has not yet been evaluated; thus, we aimed to examine the influence of chronic zoledronate (ZOL) administration on the periosteal microcirculatory consequences of hindlimb IR in osteopenic rats., Materials and Methods: Twelve-week-old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated, and ZOL (80 μg/kg iv, weekly) or a vehicle was administered for 8 weeks, 4 weeks after the operation. At the end of the pre-treatment protocols, 60-min limb ischemia was induced, followed by 180-min reperfusion. Leukocyte-endothelial interactions were quantitated in tibial periosteal postcapillary venules by intravital fluorescence videomicroscopy. CD11b expression of circulating polymorphonuclear leukocytes (PMN, flow cytometry) and plasma TNF-alpha levels (ELISA) were also determined. Two-way RM ANOVA followed by the Holm-Sidak and Dunn tests was used to assess differences within and between groups, respectively., Results: Limb IR induced significant increases in PMN rolling and firm adhesion in sham-operated and OVX rats, which were exacerbated temporarily in the first 60 min of reperfusion by a ZOL treatment regimen. Postischemic TNF-alpha values showed a similar level of postischemic elevations in all groups, whereas CD11b expression only increased in rats not treated with ZOL., Conclusions: The present data do not show substantial postischemic periosteal microcirculatory complications after chronic ZOL treatment either in sham-operated or OVX rats. The unaltered extent of limb IR-induced local periosteal microcirculatory reactions in the presence of reduced CD11b adhesion molecule expression on circulating PMNs, however, may be attributable to local endothelial injury/activation caused by ZOL.

Background: Surgical reconstruction of large bone defects with structural bone allografts can restore bone stock but is associated with complications such as nonunion, fracture, and infection. Vascularized reconstructive techniques may provide an alternative in the repair of critical bone defects; however, no studies specifically addressing the role of vascularized periosteal flaps in stimulating bone allograft revascularization and osseointegration have been reported., Questions/purposes: (1) Does a vascularized periosteal flap increase the likelihood of union at the allograft-host junction in a critical-size defect femoral model in rats? (2) Does a vascularized periosteal flap promote revascularization of a critical-size defect structural bone allograft in a rat model? (3) What type of ossification occurs in connection with a vascularized periosteal flap?, Methods: Sixty-four rats were assigned to two equal groups. In both the control and experimental groups, a 5-cm critical size femoral defect was created in the left femur and then reconstructed with a cryopreserved structural bone allograft and intramedullary nail. In the experimental group, a vascularized periosteal flap from the medial femoral condyle, with a pedicle based on the descending genicular vessels, was associated with the allograft. The 32 rats of each group were divided into subgroups of 4-week (eight rats), 6-week (eight rats), and 10-week (16 rats) followup. At the end of their assigned followup periods, the animals were euthanized and their femurs were harvested for semiquantitative and quantitative analysis using micro-CT (all followup groups), quantitative biomechanical evaluation (eight rats from each 10-week followup group), qualitative confocal microscopic, backscattered electron microscopic, and histology analysis (4-week and 6-week groups and eight rats from each 10-week followup group). When making their analyses, all the examiners were blinded to the treatment groups from which the samples came., Results: There was an improvement in allograft-host bone union in the 10-week experimental group (odds ratio [OR], 19.29 [3.63-184.50], p < 0.05). In contrast to control specimens, greater bone neoformation in the allograft segment was observed in the experimental group (OR [4-week] 63.3 [39.6-87.0], p < 0.05; OR [6-week] 43.4 [20.5-66.3], p < 0.05; OR [10-week] 62.9 [40.1-85.7], p < 0.05). In our biomechanical testing, control samples were not evaluable as a result of premature breakage during the embedding and assembly processes. Therefore, experimental samples were compared with untreated contralateral femurs. No difference in torsion resistance pattern was observed between both groups. Both backscattered electron microscopy and histology showed newly formed bone tissue and osteoclast lacunae, indicating a regulated process of bone regeneration of the initial allograft in evaluated samples from the experimental group. They also showed intramembranous ossification produced by the vascularized periosteal flap in evaluated samples from the experimental group, whereas samples from the control group showed an attempted endochondral ossification in the allograft-host bone junctions., Conclusions: A vascularized periosteal flap promotes and accelerates allograft-host bone union and revascularization of cryopreserved structural bone allografts through intramembranous ossification in a preclinical rat model., Clinical Relevance: If large-animal models substantiate the findings made here, this approach might be used in allograft reconstructions for critical defects using fibular or tibial periosteal flaps as previously described.

Strength training induces not only muscle growth but also increased bone strength, a change that is expected to be associated with increased bone blood flow. However, the effects of exercise on contractile properties of bone microvascultaure have not been investigated. Once-a-week strength training with electrical muscle stimulation was applied unilaterally to tibialis anterior muscle of guinea pigs, while muscle force was measured from both legs to compare their muscle strength and endurance. After 10 weeks of training, changes in the arteriolar diameters of isolated periosteum taken from both trained and non-trained legs were measured using a video tracking system. Electrical field stimulation evoked a phasic constriction followed by a sustained dilatation in periosteal arterioles of trained legs, while triggering only vasoconstriction in the arterioles of non-trained legs. In trained leg arterioles, phentolamine, an α-adrenoceptor antagonist, inhibited both the constriction and dilatation. Prazosin, an α 1 -adrenoceptor antagonist, inhibited only the constriction, while yohimbine, α 2 -adrenoceptor antagonist, or l-nitro arginine (L-NA), a nitric oxide (NO) synthase inhibitor, inhibited the dilatation. In non-trained leg arterioles, phentolamine or prazosin largely suppressed the constriction, but failed to unmask any dilatation. Consistently, noradrenaline (NAd)-induced arteriolar constriction was enhanced and prolonged by L-NA in trained but not non-trained side arterioles. Thus, NAd released from sympathetic nerves appears to activate endothelial α 2 -adrenoceptors to release NO resulting in the sustained dilatation of periosteum arterioles from trained leg. The altered sympathetic vasomotor function would facilitate the blood supply to the bone and may contribute to the exercise-induced bone strength gain., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Nonunion is a common complication of lateral condyle humeral (LCH) fractures in children. In situ fixation with a screw and bone grafting is the classically-recommended method of treatment. The purpose of this study is to analyze the feasibility of obtaining a vascularized periosteal flap obtained from the lateral humerus and based on the posterior collateral radial vessels (PCRV). Second, to report the results after the application in two pediatric cases., Methods: Periosteal branches of PCRV were studied in ten upper limbs from fresh human cadavers. Then, two children with LCH nonunion were treated with this flap., Results: The PCRV provided mean of 5.3 anterior periosteal branches (range 4-7) with a mean distance between them of 19.1 mm (range 5-29 mm) and 5.7 posterior periosteal branches (range 3-7) with a mean distance between them of 15.9 mm (range 6-33 mm. PCRV distally anastomosed to the interosseous recurrent artery and the radial recurrent artery, creating a vascular net over the lateral condyle and allowing for the design of a reverse vascularized humeral periosteal flap (VHPF). Abundant periosteal callus and rapid consolidation were achieved in both children. No bone fixation or grafting was necessary., Conclusions: VHPF might be considered a viable biological surgical option to promote bone healing in LCH nonunions in children, while avoiding the need for bone fixation and the donor morbidity associated with bone grafting., (© 2017 Wiley Periodicals, Inc.)

Various synthetic bone substitutes are not suitable for reconstructing critical-size bone defects. This study tested whether a bioglass-β-tricalcium phosphate (β-TCP) monoblock is effective for repairing critical-size segmental bone defects if combined with a vascularized periosteal flap and bone morphogenetic protein (BMP)-2. A femoral osteotomy with a gap size of 20 mm was created and stabilized using a plate in 40 rabbits.The defect was left untreated (group A) or repaired using a monoblock (group B), a monoblock with a vascularized periosteal flap (group C), or a monoblock with a vascularized periosteal flap and BMP-2 (group D). Bone regeneration, vascularization and monoblock degradation were analyzed after four and eight weeks using x-ray, hematoxylin-eosin, CD34 immunohistochemical and Masson's trichrome staining observation and histometric evaluation. The radiographic grading score showed a time-dependent increase from weeks 4 to 8. At 8-week postoperative, the total new regenerated bone in groups C and D was 20.0 ± 0.3 and 55.5 ± 8.0 mm 2 , respectively, which was significantly greater than in group B. Conversely, group D showed less residual monoblock than did group C. An increase in microvessel density was also observed in groups C and D compared with group B at 4 and 8 weeks postoperative, respectively. This study suggests that bioglass-β-TCP monoblock alone exhibits poor potential to repair a 20-mm femoral defect. However, supplementation with a vascularized periosteal flap and BMP-2 led to effective vascularization and reliable bone regeneration throughout the monoblock, with concordant material degradation in a timely manner. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2148-2156, 2018., (© 2017 Wiley Periodicals, Inc.)

Purpose: In intraoral bone grafting, tension-free coverage of the recipient site with periosteal flap results in optimal wound closure. Tissue expansion could be a suitable modality to obtain soft tissue in the oral cavity. The aim of this study was to assess the histology of the periosteum after subperiosteal expansion in the rabbit scalp., Materials and Methods: In this animal study, 6 rectangular tissue expanders were placed in the skulls of 6 male white New Zealand rabbits; in 6 control rabbits, an incision was made to the periosteum but no expansion was performed. Three months after the surgeries, the rabbits were sacrificed and tissue samples were stained with hematoxylin and eosin and Masson trichrome., Results: The number of osteoblasts, fibroblasts, and blood vessels and the density of collagen fibers were significantly increased in the experimental group compared with the control group (P < .001)., Conclusions: Subperiosteal tissue expansion in the rabbit scalp markedly increased the histologic components of the periosteum involved in bone regeneration., (Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Our aim was to examine the effects of ischemic preconditioning (IPC) on the local periosteal and systemic inflammatory consequences of hindlimb ischemia-reperfusion (IR) in Sprague-Dawley rats with chronic estrogen deficiency (13 weeks after ovariectomy, OVX) in the presence and absence of chronic 17beta-estradiol supplementation (E2, 20 µg kg -1 , 5 days/week for 5 weeks); sham-operated (non-OVX) animals served as controls. As assessed by intravital fluorescence microscopy, rolling and the firm adhesion of polymorphonuclear neutrophil leukocytes (PMNs) gave similar results in the Sham + IR and OVX + IR groups in the tibial periosteal microcirculation during the 3-h reperfusion period after a 60-min tourniquet ischemia. Postischemic increases in periosteal PMN adhesion and PMN-derived adhesion molecule CD11b expressions, however, were significantly reduced by IPC (two cycles of 10'/10') in Sham animals, but not in OVX animals; neither plasma free radical levels (as measured by chemiluminescence), nor TNF-alpha release was affected by IPC. E2 supplementation in OVX animals restored the IPC-related microcirculatory integrity and PMN-derived CD11b levels, and TNF-alpha and free radical levels were reduced by IPC only with E2. An enhanced estrogen receptor beta expression could also be demonstrated after E2 in the periosteum. Overall, the beneficial periosteal microcirculatory effects of limb IPC are lost in chronic estrogen deficiency, but they can be restored by E2 supplementation. This suggests that the presence of endogenous estrogen is a necessary facilitating factor of the anti-inflammatory protection provided by limb IPC in females. The IPC-independent effects of E2 on inflammatory reactions should also be taken into account in this model. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:97-105, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The use of different membranes is common in dentoalveolar surgery. Absorbable and nonabsorbable membranes are used, often beneath the periosteum, to fulfil different functions (as barriers, patches, or spacers). It is still unclear to what extent such membranes affect the biology of the periosteum and what role is played by piezoelectric devices during preparation of the periosteum. We placed two different membranes (absorbable and nonabsorbable) underneath the periosteum of rat calvaria. We prepared the periosteum using different methods (piezoelectric device vs mechanical device). We then examined and analyzed periosteal microcirculation over a period of 28 days. A clear difference was observed between the two methods when used with absorbable membranes: The piezoelectric device offered advantages. Absorbable membranes maintain considerably more local periosteal microcirculation and should be given preference. In addition, we observed an advantage to using a piezoelectric device for periosteal dissection. Therefore, this method should also be used more widely.

Background: Few studies have been published reporting risk factors for flap necrosis after primary palatoplasty in patients with cleft palate. This complication is rare, and the event is a disaster for both the patient and the surgeon. This study was performed to explore the associations between different risk factors and the development of flap necrosis after primary palatoplasty in patients with cleft palate., Methods: This is a case-control study. A 20 years retrospective analysis (1994-2015) of patients with nonsyndromic cleft palate was identified from medical records and screening day registries). Demographical and risk factor data were collected using a patient´s report, including information about age at surgery, gender, cleft palate type, and degree of severity. Odds ratios and 95% confident intervals were derived from logistic regression analysis., Results: All cases with diagnoses of flap necrosis after primary palatoplasty were included in the study (48 patients) and 156 controls were considered. In multivariate analysis, female sex, age (older than 15 years), cleft type (bilateral and incomplete), and severe cleft palate index were associated with significantly increased risk for flap necrosis., Conclusions: The findings suggest that female sex, older age, cleft type (bilateral and incomplete), and severe cleft palatal index may be associated with the development of flap necrosis after primary palatoplasty in patients with cleft palate.

The periosteal arterioles of the compact bone may play a critical role in bone growth. To explore the contractile properties of tibial arterioles, spontaneous and nerve-evoked constrictions were compared in preparations from 3-week-old and 1-year-old guinea-pigs. Changes in arteriole diameters were measured using video microscopy. Their innervation was investigated using fluorescence immunohistochemistry. Fifty per cent and 40% of tibial arterioles from 3-week-old and 1-year-old guinea-pigs, respectively, exhibited spontaneous phasic constrictions that were inhibited by 1 μM nifedipine, 10 μM cyclopiazonic acid or 100 μM 2-APB. Nerve-evoked phasic constrictions in both age groups were largely suppressed by phentolamine (1 μM), an α-adrenoceptor antagonist, or sympathetic neurotransmitter depletion using guanethidine (10 μM) but were enhanced by spanttide (1 μM), a substance P receptor antagonist, or L-nitro arginine (L-NA; 100 μM), an inhibitor of nitric oxide synthase (NOS). Nerve-evoked constrictions in 1-year-old animals were smaller than those in younger animals but greatly enhanced by L-NA. Immunohistochemistry revealed sympathetic and substance P-positive primary afferent nerves running along the arterioles as well as endothelial NOS expression in both age groups. Spontaneous arteriolar constrictions appear to rely on both Ca 2+ release from the sarcoplasmic reticulum and Ca 2+ influx through L-type Ca 2+ channels. Noradrenaline released from sympathetic nerves triggers arteriolar constriction, while substance P released from primary afferent nerves dilates the arterioles by releasing nitric oxide (NO), presumably from the endothelium. Thus, the enhanced endothelial NO release in adult guinea-pigs may be important to increase the blood supply to meet the increased metabolic demands during bone growth.

Purpose: The purpose of this report is to evaluate the results of extending vascularized fibular grafts (VFG) with vascularized periosteum (VPG) in bone defect reconstruction in children., Methods: Retrospective study of 10 children, mean age at surgery was 9.8 years (range, 4-16 years). Origin of one defect was oncological (n = 5), septical (n = 2), traumatic (n = 2), or congenital (n = 1). In five cases the flap consisted of a VFG and a vascularized epiphyseal transfer (VFET) in five. Mean bone defect was 8.5 cm .Mean length of the vascularized periosteal extension was 5.5 cm (range 3.5-8) for VFET, 4.8 cm for VFG (range 3-8). Bone union was assessed with monthly radiographs., Results: Radiographs showed a periosteal callus at 4 weeks in all cases. Bone union was achieved at a mean of 8.4 weeks (range 4-12). Donor site complications included two cases of flexor hallucis longus contracture, and one case of surgical wound marginal necrosis following FVG. One transient tibialis anterior weakness and one tibialis anterior contracture occurred following VFET harvest. None required surgical treatment. Mean follow-up was 28.7 months (range 7-72)., Conclusions: The association of a vascularized periosteal extension with fibular flaps seems to accelerate flap to recipient bone union. © 2016 Wiley Periodicals, Inc. Microsurgery 37:410-415, 2017., (© 2016 Wiley Periodicals, Inc.)

Apart from its nutritive functions, the periosteum critically affects bone regeneration via its stem/osteoprogenitor cell content. Normal healing after bone fractures, trauma-orthopedic interventions and invasive dental procedures is critically linked to the reestablishment of the periosteal microcirculation, but the reconstruction, replacement or repair of lost tissues may also be performed with autologous periosteum. Besides the initiation of cell differentiation during bone repair and remodeling processes, the periosteum together with the endosteum plays significant roles in the pathogenesis of both hormone-related and trauma-induced osteoporotic alterations in the bone metabolism. Nevertheless, the axial bones, and in particular the jawbones, and the appendicular bones display differences not only in their blood supply and fracture healing characteristics, but also in respect of the development of osteoporosis and their reactions to treatment modalities (i.e. bisphosphonates). These reactions may also be linked to the differences in periosteal microcirculatory reactions. The present overview summarizes the relevant data of microcirculatory studies focusing on the periosteal reactions in different anatomical locations together with the optimal background methodologies, study models and the most significant observations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In addition to conveying the forces of attaching muscles and ligaments to the zygomatic and temporal bones, the arch periosteum is responsible for lateral apposition and medial resorption during the growth period. In this contribution, we describe the vasculature of the zygomatic arch in young pigs (Sus scrofa dom.) in order to understand the relationship of osseous and periosteal vessels to each other, to surrounding tissues, and to patterns of modeling. Subjects 2-6 weeks of age were perfused with vascular fill; some also received the vital bone label calcein. Whole mounts were prepared of the decalcified bony arch and of its lateral periosteum. Undecalcified arches were plastic-embedded and thick-sectioned. Additional observations on cell replication were made using material from a previous study. The osseous and periosteal vascular supplies were largely independent, joined only by a fine network at the tissue interface. Osseous vessels entered the medial side of the arch through clusters of nutrient foramina. The intraosseous branching pattern resembled the direction of appositional growth, which in turn describes the disposition of bony trabeculae in older pigs. In contrast, vessels arrived at the periosteum via muscles and ligaments and thus its perfusion may partially depend on functional activity. The open weave of periosteal vessels bore little similarity to bone architecture, especially for the temporal bone, but the appositional lateral periosteum showed indications of angiogenesis, whereas the thinner, resorptive periosteum on the medial side featured composite, possibly fusing vessels at the bone surface. Anat Rec, 299:1661-1670, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: The importance of the periosteum in fracture healing is well-known. Preserving periosteal vascularisation is essential during internal plate fixation of fractures., Methods: This was an experimental randomised, controlled animal study on nine sheep. Standard dynamic compression plate (DCP) and four different newly designed reefed plates, with different plate-bone contact surface areas and different reef directions, were fixated on to the tibia or radius. After two weeks the plates were removed and the underlying periosteum was analysed. Blood vessels were marked by immunohistochemical staining (CD31 and CD34), microphotographs were taken and blood vessels counted to calculate blood vessel density., Results: Median blood vessel density beneath the standard plate was significantly lower than in the intact periosteum (18.0 vs 27.7mm(3)/cm(3)). Blood vessel density in the periosteum beneath plates with reefs was significantly increased compared with the intact periosteum, and was highest beneath the plate with the lowest bone-plate contact area and crosswise reefs (51.5mm(3)/cm(3)), followed by plates with transverse, oblique and longitudinal reefs, respectively. The direction of the reefs did not have much influence on the periosteal capillary network. Lower contact surface area seems to be the main factor that increases blood vessel density beneath the plates., Conclusions: The results show that plates with lower contact surface area stimulate angiogenesis in the underlying periosteum, which results in much higher blood vessel density compared with standard DCP. A randomised clinical trial is needed to prove the clinical relevance of these findings., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The use of the Masquelet technique in the repair of large bone defects has gained increased acceptance in recent years. The core of this technique is the induction of granulation tissue membrane formation and the implantation of an autologous cancellous bone to reconstruct bone defects in the membrane. In this study, we purpose to explore the structure of induced membrane and the content of growth factors as well to compare between the structure and the effects on osteogenesis of induced membranes and the periosteum in animal models., Methods: Bilateral radial bone defects were generated in 32 healthy adult rabbits. The defects were implanted with bone cement. The induced membranes and periosteum were removed after 2, 4, 6, and 8 weeks. Thereafter, hematoxylin-eosin staining (HE) and an enzyme-linked immunosorbent assay (ELISA) were performed to detect vascular endothelial growth factor (VEGF), angiotensin II (ANG-II), bone morphogenetic protein 2 (BMP2), fibroblast growth factor 2 (FGF2), and prostaglandin E2 (PGE2). Proteins isolated from total cell lysates were cultured with mesenchymal stem cells to test the cell proliferation and alkaline phosphatase activity using epimysium as a control., Results: The induced membrane and periosteum exhibited similar structures and growth factor levels after 4 and 6 weeks. The highest concentration of BMP-2 and VEGF in the induced membranes occurred in week 6, and FGF-2 and ANG-II concentrations peaked in week 4. The thickness and vascular density of induced membranes gradually decreased with time., Conclusion: Induced membrane matured between the 4th and the 6th week and secreted growth factors to promote osteogenesis. The matured induced membrane and periosteum had similar structures and abilities to promote the osteogenesis of mesenchymal stem cells. However, the induced membrane was thicker than the periosteum.

Objectives: Nitrogen-containing bisphosphonates induce osteonecrosis mostly in the jaw and less frequently in other bones. Because of the crucial role of periosteal perfusion in bone repair, we investigated zoledronate-induced microcirculatory reactions in the mandibular periosteum in comparison with those in the tibia in a clinically relevant model of bisphosphonate-induced medication-related osteonecrosis of the jaw (MRONJ)., Materials and Methods: Sprague-Dawley rats were treated with zoledronate (ZOL; 80 i.v. μg/kg/week over 8 weeks) or saline vehicle. The first two right mandibular molar teeth were extracted after 3 weeks. Various systemic and local (periosteal) microcirculatory inflammatory parameters were examined by intravital videomicroscopy after 9 weeks., Results: Gingival healing disorders (∼100%) and MRONJ developed in 70% of ZOL-treated cases but not after saline (shown by micro-CT). ZOL induced significantly higher degrees of periosteal leukocyte rolling and adhesion in the mandibular postcapillary venules (at both extraction and intact sites) than at the tibia. Leukocyte NADPH-oxidase activity was reduced; leukocyte CD11b and plasma TNF-alpha levels were unchanged., Conclusion: Chronic ZOL treatment causes a distinct microcirculatory inflammatory reaction in the mandibular periosteum but not in the tibia. The local reaction in the absence of augmented systemic leukocyte inflammatory activity suggests that topically different, endothelium-specific changes may play a critical role in the pathogenesis of MRONJ., Clinical Relevance: This model permits for the first time to explore the microvascular processes in the mandibular periosteum after chronic ZOL treatment. This approach may contribute to a better understanding of the pathomechanism and the development of strategies to counteract bisphosphonate-induced side effects.

Background: The combined latissimus dorsi-serratus anterior-rib (LD-SA-rib) free flap provides a large soft-tissue flap with a vascularized bone flap through a solitary vascular pedicle in a one-stage reconstruction., Methods: Seven LD-SA-rib free flaps were performed in seven patients to reconstruct concomitant bone and extensive soft-tissue defects in the lower extremity (tibia, five; femur, one; foot, one). The patients were all male, with an average age of 34 years (range, 20-48 years). These defects were secondary to trauma in five patients and posttraumatic osteomyelitis in two patients., Results: All flaps survived and achieved bony union. The average time to bony union was 9.4 months. Bone hypertrophy of at least 20% occurred in all flaps. All patients achieved full weight-bearing ambulation without aid at an average duration of 23.7 months. Two patients developed stress fractures of the rib flap. There was no significant donor site morbidity, except for two patients who had pleural tears during harvesting of the flap., Conclusion: The LD-SA-rib flap provides a large soft-tissue component and a vascularized bone flap for reconstruction of composite large soft-tissue defects with concomitant bone defects of the lower extremity in a one-stage procedure., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: To compare tibial fracture healing in rats with or without soft-tissue attachment., Methods: The left tibias of 30 Wistar rats were osteotomised and equally randomised into 3 groups. In the avascular segmental fracture group, an 8-mm bone segment were first removed and then immediately put back. In the vascular segmental fracture group, the 8-mm bone segment was not displaced, with periosteal and muscular attachments. In the simple fracture group, a simple fracture in the middle tibia was made. All tibias were then stabilised with an intramedullary nail through the patellar tendon, and the wound was closed with sutures. After 8 weeks, all left tibias and 9 of the intact right tibias were harvested. Bone mineral content and density of the calluses were assessed using dual energy X-ray absorptiometry scanning. The maximum torsional strength, rigidity, and energy to failure of the tibias were measured., Results: All tibias healed (callus formation), without mal-union or pin migration. The 3 groups did not differ significantly in terms of torsional strength, rigidity, energy to failure, bone mineral content, and bone mineral density. The mean torsional strength of the 9 intact tibias was significantly higher than the healed tibias (14.9 vs. 10.6 Nmm, p=0.021)., Conclusion: Soft-tissue detachment from bone segments did not impair bone healing in rats.

Bone nonunion in the pediatric population usually occurs in the context of highly unfavorable biological conditions. Recently, the vascularized fibular periosteal flap has been reported as a very effective procedure for treating this condition. Even though a vascularized tibial periosteal graft (VTPG) was described long ago and has been successfully employed in one adult case, there has been no other report published on the use of this technique. We report on the use of VTPG, pedicled in the anterior tibial vessels, for the treatment of two complex pediatric bone nonunion case: a recalcitrant supracondylar femoral pseudarthrosis secondary to an infection in an 11-year-old girl, and a tibial nonunion secondary to a failed bone defect reconstruction in a 12-year-old girl. Rapid healing was obtained in both cases. In the light of the data presented, we consider VTPG as a valuable surgical option for the treatment of complex bone nonunions in children., (© 2014 Wiley Periodicals, Inc.)

Objective: The periosteum plays an important role in bone physiology, but observation of its microcirculation is greatly limited by methodological constraints at certain anatomical locations. This study was conducted to develop a microsurgical procedure which provides access to the mandibular periosteum in rats., Methods: Comparisons of the microcirculatory characteristics with those of the tibial periosteum were performed to confirm the functional integrity of the microvasculature. The mandibular periosteum was reached between the facial muscles and the anterior surface of the superficial masseter muscle at the external surface of the mandibular corpus; the tibial periosteum was prepared by dissecting the covering muscles at the anteromedial surface. Intravital fluorescence microscopy was used to assess the leukocyte-endothelial interactions and the RBCV in the tibial and mandibular periosteum. Both structures were also visualized through OPS and fluorescence CLSM., Results: The microcirculatory variables in the mandibular periosteum proved similar to those in the tibia, indicating that no microcirculatory failure resulted from the exposure technique., Conclusion: This novel surgical approach provides simple access to the mandibular periosteum of the rat, offering an excellent opportunity for investigations of microcirculatory manifestations of dentoalveolar and maxillofacial diseases., (© 2014 John Wiley & Sons Ltd.)

Introduction: Subperiosteal preparation using a periosteal elevator leads to disturbances of local periosteal microcirculation. Soft-tissue damage can usually be considerably reduced using piezoelectric technology. For this reason, we investigated the effects of a novel piezoelectric device on local periosteal microcirculation and compared this approach with the conventional preparation of the periosteum using a periosteal elevator., Material and Methods: A total of 20 Lewis rats were randomly assigned to one of two groups. Subperiosteal preparation was performed using either a piezoelectric device or a periosteal elevator. Intravital microscopy was performed immediately after the procedure as well as three and eight days postoperatively. Statistical analysis of microcirculatory parameters was performed offline using analysis of variance (ANOVA) on ranks (p<0.05)., Results: At all time points investigated, intravital microscopy demonstrated significantly higher levels of periosteal perfusion in the group of rats that underwent piezosurgery than in the group of rats that underwent treatment with a periosteal elevator., Conclusion: The use of a piezoelectric device for subperiosteal preparation is associated with better periosteal microcirculation than the use of a conventional periosteal elevator. As a result, piezoelectric devices can be expected to have a positive effect on bone metabolism., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: To compare the different resorption patterns between resorbable membrane barrier and periosteum after iliac block bone grafting radiographically and histologically., Methods: Eighteen mature male rabbits weighing from 2.0 to 2.5 kg were used. The recipient site was the rabbit skull, and autogenous iliac bone was used as the grafting material. The harvested iliac block bones were divided in the following groups: autogenous iliac block bone with preservation of the periosteum (the periosteum group), autogenous iliac block bone covered with a resorbable collagen membrane (Biomesh®, Samyang Co, Korea) after removing the periosteum (the collagen membrane group), and autogenous iliac block bones with removal of the periosteum (the control group). In each experimental group, periosteum or resorbable collagen membrane of the donor site was fixed directed to the periosteum of the recipient site. The specimens were examined macroscopically, radiographically, histologically, and histomorphometrically at every 2, 4, and 8 weeks., Results: All groups presented excellent bone graft healing state without inflammation, dehiscence, or displacement. The radiolucency increased from mild to moderate in all groups over the experiment. The mean thickness of the upper end of the cortical iliac bone graft was statistically significantly different between the control group and the periosteum group, between the four-week and eight-week control group, and between the four- week and eight-week periosteum group (p & 0.05)., Conclusion: This study suggests that both the periosteum and the resorbable collagen membrane may help to prevent soft tissue infiltration into the bone graft and to reduce bone graft resorption compared to block graft alone.

Purpose: This study sought to confirm, through histologic evaluation, the vitality and viability of the island osteoperiosteal flap (i-flap) in a rabbit tibia model., Materials and Methods: In four rabbits, an osteotomy was performed on the tibial aspect of the right leg. A bone flap was raised, but the periosteal attachment was kept intact. The free-floating i-flap was separated from the rest of the bone by a silicone sheet. The rabbits were to be sacrificed after 1, 2, 4, and 8 weeks and histologic samples examined., Results: All surgeries were accomplished successfully; however, three animals showed fractured tibiae within a few days after surgery and were sacrificed immediately after the fractures were discovered. The fourth rabbit was sacrificed at 4 weeks. Histologic specimens showed vital new bone in the i-flap area and signs of remodeling in the transition zone and the original basal bone., Conclusion: The i-flap remained vital. This suggests potential for use in bone augmentation strategies, particularly for the alveolar split procedure.

Background: In microvascular transfer of fibular osteocutaneous flap for mandible reconstruction after cancer ablation, good bone union is necessary to allow timely radiation therapy after surgery. As the area of bone contact between fibula and the original mandible at the edge of the mandibular defect is small, a periosteal excess at both ends of the fibula covering the bone junction can be used to increase the chance of bone union. The purpose of this study is to investigate whether a periosteal excess surrounding both ends of the fibula flap can provide better blood supply and, therefore, ensure bone union and wound healing at 6 weeks after surgery and before radiation therapy initiation., Patients and Methods: The transfer of fibular osteocutaneous flap with periosteal excess was only applied to reconstruct segmental mandibular defects. As a consequence, only cases in which osteotomy of fibula was not performed were included in this study. A total of 34 fibular flaps without osteotomies were performed between 2000 and 2008; 17 with and 17 without the periosteal excess. The bone union was evaluated in terms of osseous callus formation using X-rays and CT three-dimensional images at 6 weeks after surgery, and results were assessed by three independent radiologists., Results: There was a significant difference between reconstructions with and without the periosteal excess in terms of bone union (P = 0.022). With reference to postoperative complications, the group reconstructed without periosteal excess presented a higher number of complications, mainly consisting of partial and total flap necrosis, respectively six (35.29%) and two (11.76%) cases. In the group reconstructed with periosteal excess, no loss of the skin island has occurred. A significant difference was observed in terms of partial flap necrosis (P = 0.024), while the other complications did not reveal a statistically significant difference (P > 0.05)., Conclusions: The use of a periosteal excess at both ends of the fibula flap provides better blood supply and is, therefore, able to ensure good bone healing and skin paddle survival regardless of the radiotherapy., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Joints are privileged compartments that enjoy increased protection against the inflammatory reactions affecting the extremities. We hypothesized that the functional characteristics of the microvasculature would contribute to the differential defensive potential of the synovial membrane., Methods: We investigated the synovial microcirculatory reactions and compared them with those of the tibial periosteum in response to 60 min of total limb ischemia, followed by 180 min of ischemia-reperfusion (IR) in rats. Carrageenan/kaolin-induced knee monoarthritis, a neutrophil-driven synovial inflammation model, served as the positive control., Results: IR brought about a significant reduction in red blood cell velocity in the capillaries and increases in rolling and adherence of the neutrophil leukocytes in the postcapillary venules (intravital microscopy), in adhesion molecule expression (intercellular adhesion molecule-1 immunohistochemistry) and in xanthine oxidoreductase activity in the periosteum. These changes were also pronounced in carrageenan/kaolin-induced monoarthritis but were almost completely absent in the synovium after the IR challenge. Most importantly, even after IR and in carrageenan/kaolin monoarthritis, the synovial microcirculation was characterized by significantly greater red blood cell velocities than that in the periosteum under resting conditions., Conclusions: The ischemic duration, which significantly affected the functional integrity of the periosteal microcirculation, did not bring about a marked deterioration in that of the synovial membrane, suggesting that the synovial microcirculation is less endangered to the consequences of short-term tourniquet exposure than the periosteum. The greater microcirculatory red blood cell velocities and lower IR-induced endothelial expression of intercellular adhesion molecule-1 in the synovial membrane might explain the greater resistance of this compartment to the inflammatory consequences of IR., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction/aims: Our aim was to characterize the periosteal microvascular reaction induced by the destruction of endosteal vasculature by reaming, and to monitor the time sequence of the events. We have also compared the microcirculatory effects of different implant materials that are most frequently employed in human endoprosthetics., Materials and Methods: The right tibia of male Wistar rats was reamed by microsurgical means and implanted with titanium, steel-alloy or polyethylene nails. Intravital videomicroscopic examinations of the anteromedial and anterolateral surfaces of the tibial periosteum were performed to evaluate the changes in the overall vascular and capillary densities. Microscopic mechanical tests were used to assess the stability of the implants. In control groups, reaming without nailing was performed and the microvascular changes were examined 6 and 12 weeks after surgery., Results: Reaming alone caused a significant increase in the vascular density of the anteromedial periosteum and a bilateral increase in capillary density. Vascular density at the anteromedial side was increased after all of the implant materials applied, while only polyethylene induced remarkable increases in the capillary and vascular densities at the anterolateral side. Furthermore, polyethylene did not bring about osseointegration., Conclusions: Enhanced periosteal angiogenesis could be demonstrated after 12 weeks following tibial reaming. The compensatory microvascular reactions evoked by destruction of endosteal microcirculation of long bones are not influenced by osseo-integrative implant materials, but materials of poor osseointegration properties induce considerable compensatory increases in the microvascular density of the periosteum.

Background: Segmental bone defect is still a challenge to orthopedic surgeons. Currently available therapies for segmental bone defects have some drawbacks. Tissue engineering using pluripotent stem cells is a new, promising method for bone repair. The present study aims to promote the effect of bone defect repair using the tissue engineered bone in combination with vascularized periosteal flaps., Methods: The adenoviral vector carrying Cbfa1 transduced rabbit adipose-derived mesenchymal stem cells and gene modified tissue engineering bone (GMB) were constructed. Rabbits with radial defects were implanted with the GMB together with vascularized periosteum (group A); or GMB with free periosteum (group B); or GMB (group C), and scaffold (group D). The bone repair effect was evaluated at 4, 8, or 12 wk, respectively, after the operations., Results: Cbfa1 proteins were strongly expressed in adipose stem cells (ADSCs) that formed a stratified network on the inner surface of the polylactic acid/ polycaprolacton (PLA/PCL) pores. Bone repair was well achieved in the rabbits treated with the Cbfa1-expressing ADSCs and vascularized flap that was markedly better than those treated with either Cbfa1-expressing ADSCs alone or with vascularized flap alone., Conclusions: Combination with implanting the Cbfa1 gene-modified tissue-engineered bone and vascularized periosteum can better repair the segmental bone defects by stimulating osteogenesis, osteoinduction, and osteoconduction than using either one of the approaches., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Intramedullary reaming and nailing of long bones impairs the endosteal circulation, often causing necrosis of the inner region of the bone cortex. We hypothesized that compensatory hypertrophy of the periosteal microcirculation may develop in response to mechanical destruction of the endosteum, and that this may affect bone survival in these circumstances. In these studies, nailing was performed with materials that affect regeneration of the endosteum differently, and the effects on the tibial periosteal microvasculatory organization were examined., Methods: In male Wistar rats, the right tibia was reamed and implanted with an inert titanium nail or a less osseointegrative polyethylene nail; the contralateral tibial endosteum was destroyed by reaming. Reaming without nailing or sham operation was performed on both extremities in two other groups of rats. Twelve weeks later, the anteromedial and anterolateral surfaces of the tibias were exposed by a microsurgical technique. The structural characteristics of the periosteal microcirculation (vessel density and distribution of vessel diameters) were determined by intravital videomicroscopy and computer-assisted analysis. The stability of the implants was assessed on the basis of grades 0-2 on a qualitative scale., Results: Tibial reaming alone caused significant increases in overall blood vessel and capillary densities in the periosteum compared with those of the intact tibias. Implantation with a titanium nail resulted in firm embedding of the nail and caused changes in the periosteal vasculature similar to those after reaming alone. In contrast, implantation of a polyethylene nail was followed by the development of marked instability of the endomedullary implant and significant increases in the percentage of capillaries and the vessel density in the periosteum., Conclusions: Destruction of the endosteal microcirculation per se brings about an increase in periosteal vascular density, which is further augmented if implantation is performed with a material which delays regeneration of the endosteal circulation.

Purpose: To compare the structural and cellular differences of the periosteum from different parts of the mandible in minipigs by use of histologic and immunohistochemical methods to confirm the areas in which periosteal osteogenesis in situ can be used to treat mandible defects., Materials and Methods: Three minipigs were killed, and the left mandible of each was retrieved with the periosteum remaining and then fixed, decalcified, and embedded. The specimens were cut from the buccal and lingual sides of the ramus, angle, and body of the mandible and the mentum. Sections were stained with hematoxylin-eosin and antibodies for Stro-1 (stem cell marker) and vWF (endothelial cell marker). For each periosteal area, the thickness and number of positive cells for each antibody were measured and analyzed., Results: The mentum and mandibular angle periostea were thicker than those of the body and ramus. In addition, there were more blood vessels in the periostea of the mentum and mandibular body than the angle and ramus. There were more Stro-1-positive cells in the ramus periosteum than the mentum, body, and angle of the mandibles., Conclusions: The structure and cell populations of the periosteum appear to be site specific. Therefore we suggest periosteal osteogenesis in situ to treat mentum and mandibular body defects. The periosteum should be preserved as much as possible to guarantee a good healing process., (Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The periosteum in children has strong osteogenic power and is quite thick, facilitating procurement. However, it has been rarely used as a vascularized flap to enhance bone union in this age range. The purpose of this study is to assess the effectiveness of a new vascularized periosteal flap harvested from the fibula for the enhancement of bone union in the pediatric age., Methods: Thirteen vascularized fibular periosteal grafts were used in 12 children, mean age 12.6 years. Indications included the prevention of bone allograft-host junction nonunion and treatment of recalcitrant bone nonunion. In 9 instances, the periosteal flap was harvested as a free flap and in 4 as a pedicled flap. Serial radiographs and computed tomography scans were used to evaluate the progression of callus formation and bone healing., Results: All flaps were successful in promoting bone healing and achieving bone union in a mean time of 2.8 months for metaphyseal junctions and 7.1 months for diaphyseal ones, except for 1 case, which initially failed due to a pedicle torsion. It was then resolved with a second vascularized fibular periosteal grafts, with complete union after 5 months., Conclusions: Transfer of a vascularized fibular periosteal flap, either pedicled or as a free flap, is an effective treatment to enhance bone union in children in biologically unfavorable scenarios. The properties of periosteal tissue in the pediatric age are unique and its use in bone union enhancement permits new reconstructive strategies in children different from those described in adults., Level of Evidence: IV.

Background: The corticoperiosteal flap from the medial femoral condyle has become the workhorse in the management of recalcitrant nonunions with vascularized periosteum. Inclusion of the outer condylar cortex has been advocated to avoid damaging the osteogenic capacity of the periosteum and is at present an ordinary technical step in the procedure., Patients: A clinical prospective study was undertaken to evaluate the effectiveness of periosteal-only microvascular transfers from the medial femoral condyle associated with bone grafts in the treatment of recalcitrant nonunions. A group of 8 patients with periosteal-only flaps (study group) is compared with a corticoperiosteal control group (13 patients). A statistical analysis is made of the results., Results: We had 100% union rate in both the study and control groups. Evaluation of early signs of bone healing by two independent evaluators did not found differences between the groups (4.5 months in the study and 4.9 months in the control group)., Conclusions: Although not statistically significant because of the small sample size, our study might support the idea that both periosteal and corticoperiosteal flaps from the medial femoral condyle are effective, when associated with a bone graft, in the treatment of recalcitrant nonunions with small gaps. A further analysis of the results suggests, albeit no statistical significant, that structural and nonstructural bone grafts are both effective when associated with a vascularized periosteal or corticoperiosteal transfer from the medial femoral condyle.

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm(3), respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

Purpose: Loss of alveolar vertical height is one of the most challenging conditions in the field of implantology. A few augmentation techniques have been proposed to address this challenge, including guided bone regeneration, alveolar distraction osteogenesis, sandwich osteotomies and autogenous block grafting. This is a pre-clinical study of lengthening the alveolar bone height using a thin osteoperiosteal bone flap, the "island bone flap" or i-flap, to establish vitality, stability and incorporation of the augmentation material after healing., Materials and Methods: A rabbit tibia model was designed for this study and included 8 rabbits. An osteoperiosteal osteotomy was performed through the periosteum cutting 1 mm of the outer cortex of the bone in order to elevate a bone flap. The bone flap was detached, and remained attached to the periosteum as a free floating osteoperiosteal flap, and the resultant defect was filled with xenograft., Results: The histological analysis demonstrates formation of maturing trabeculae in the site of the i-flap. In cases of trauma to the bone marrow during the surgical procedure, a centripetal gradient of bone remodeling from the surgical site toward the periphery was evident, while the bony component of the i-flap maintained vital., Conclusions: Creating a free floating osteoperiosteal flap, used here with interpositional grafting in a rabbit tibia, appears to heal by both appositional modeling and creeping substitution remodeling. Volumetric augmentation persisted despite exuberant bone turnover in this animal model. This technique holds promise as a possible augmentation bone grafting approach for use in alveolar reconstruction., (Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Because omental flaps are useful for flap prefabrication and the cambium layer of the periosteum can be osteogenic, we examined whether calvarial periosteum grafted onto greater omentum of rats was osteogenic and suitable for a flap. Distal omentum was wrapped with calvarial periosteum and so the cambium faced the omentum. Grafted omentum was harvested at 1 to 9 days. In other rats, grafted omentum was elevated as a pedicled flap and moved to the abdominal subcutis, to be harvested later at 1 to 5 months after the initial surgery. Bone formation was evaluated histologically, histochemically, and radiographically. On day 3, osteoid had formed. From day 4, calvarial periosteum was revascularized by omentum and bone was forming. New bone was maintained after grafting to subcutis for 5 months. Thus, bone formed by periosteum on the omentum could be used to reconstruct defects of the bone.

Objective: It is widely known that stress conditioning can protect microcirculation and induce the release of vasoactive factors for a period of several hours. Little, however, is known about the long-term effects of stress conditioning on microcirculation, especially on the microcirculation of the periosteum of the calvaria. For this reason, we used intravital fluorescence microscopy to investigate the effects of heat shock priming on the microcirculation of the periosteum over a period of several days., Methods: Fifty-two Lewis rats were randomized into eight groups. Six groups underwent heat shock priming of the periosteum of the calvaria at 42.5°C, two of them (n = 8) for 15 minutes, two (n = 8) for 25 minutes and two (n = 8) for 35 minutes. After 24 hours, a periosteal chamber was implanted into the heads of the animals of one of each of the two groups mentioned above. Microcirculation and inflammatory responses were studied repeatedly over a period of 14 days using intravital fluorescence microscopy. The expression of heat shock protein (HSP) 70 was examined by immunohistochemistry in three further groups 24 hours after a 15-minute (n = 5), a 25-minute (n = 5) or a 35-minute (n = 5) heat shock treatment. Two groups that did not undergo priming were used as controls. One control group (n = 8) was investigated by intravital microscopy and the other (n = 5) by immunohistochemistry., Results: During the entire observation period of 14 days, the periosteal chambers revealed physiological microcirculation of the periosteum of the calvaria without perfusion failures. A significant (p < 0.05) and continuous increase in functional capillary density was noted from day 5 to day 14 after 25-minute heat shock priming. Whereas a 15-minute exposure did not lead to an increase in functional capillary density, 35-minute priming caused a significant but reversible perfusion failure in capillaries. Non-perfused capillaries in the 35-minute treatment group were reperfused by day 10. Immunohistochemistry demonstrated an increase in cytoprotective HSP70 expression in the periosteum after a 15-minute and a 35-minute heat shock pretreatment when compared with the control group. The level of HSP70 expression that was measured in the periosteum after 25 minutes of treatment was significantly higher than the levels observed after 15 or 35 minutes of heat shock exposure., Conclusion: A few days after heat shock priming over an appropriate period of time, a continuous increase in functional capillary density is seen in the periosteum of the calvaria. This increase in perfusion appears to be the result of the induction of angiogenesis.

Purpose: The medial femoral condyle (MFC) vascularized corticoperiosteal flap has been well described for the treatment of nonunion with minimal bone loss. Recent applications of this donor site as a corticocancellous flap for large intercalary defects bring into question the vascular territory of bone supplied by the descending genicular artery (DGA). This study's purpose is to delineate the proximal extent of periosteal blood supply of the medial column of the femur provided by the DGA system., Methods: In 18 cadaveric specimens, the DGA was isolated, measured, and cannulated. Using subtraction techniques of fluoroscopic angiography, the vascular network and proximal-most extent of periosteal perfusion were recorded using radiopaque contrast dye., Results: The DGA branched from the superficial femoral artery 14.2 ± 2.4 cm proximal to the joint line of the knee. The length of the vascular pedicle to its attachment onto the periosteum was 7.7 ± 2.2 cm. All specimens demonstrated a filigree of periosteal vessels dominated by a transverse and a longitudinal branch at the level of the condyle. Proximal perfusion was consistently noted by a large, longitudinal medial metaphyseal periosteal artery. The medial metaphyseal periosteal artery demonstrated that the proximal-most perfusion of the DGA was 13.7 ± 1.3 cm proximal to the joint line. Average femur length was 47.1 ± 3.1 cm. The DGA provided perfusion of 29% ± 2% of the total length of the medial femur., Conclusions: The DGA provides a large and reliable region of periosteal perfusion, suggesting that corticocancellous MFC harvest might provide the benefits of vascularized bone for large, intercalary nonunion defects conventionally treated with fibula flaps., Clinical Relevance: Harvest of MFC osseous flaps extending up to 13.7 cm proximal to the joint line can be perfused from the DGA pedicle. The MFC donor site might, therefore, be a reliable option for vascularized reconstruction of larger bone defects., (Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Objectives: Impaired vascularization in the etiopathology of aminobisphosphonate-associated osteonecrosis of the jaw (BONJ) is assumed, but evidence is lacking. This immunohistochemical study differentiated vascularization and angiogenesis in BONJ-adjacent mucoperiosteal tissue., Study Design: Twenty BONJ (after zoledronate treatment) and 20 control mucoperiosteal tissue samples were processed with an autostaining-based alkaline phosphatase-antialkaline phosphatase staining kit. Vascularization was assessed by CD31 staining and angiogenesis-related neovessels by CD105 staining. The ratio of stained capillary area to total area of visible field was assessed. Statistics included Bonferroni adjustment., Results: CD31-stained microvessels were detected in each section and CD105-stained neovessels in each control. BONJ-adjacent mucoperiosteal tissue showed significantly fewer CD105-positive vessels in capillary areas (P < .05) than control samples. CD31-stained capillary area was not significantly reduced in mucoperiosteal BONJ-samples., Conclusions: Angiogenesis is impaired in BONJ-related mucoperiosteal tissue, but vascularization remains unaffected. Vessel remodeling and neovessel formation is delayed in BONJ, resulting in impaired tissue regeneration of bisphosphonate-exposed oral mucosa., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Bone modeling and remodeling following tooth extraction has been studied extensively. The reason for bone loss during the remodeling process is multifactorial, and the primary reason for this loss is still yet to be determined. The aim of this study was to examine the type of bone and the blood supply to the buccal bone in monkeys. Six maxillary arches from six monkeys were used. The arches were divided into three sections: right posterior, anterior from canine to canine, and left posterior. Blocks were decalcified and prepared for histologic processing and examination. Modified Masson trichrome and retic staining were used. Histologic sectioning demonstrated that the blood supply to the buccal bone came from the inner (socket) side of the alveolus, the periodontal ligament, the adjacent interdental bone, and the supraperiosteal vessels emanating from the covering gingiva or mucosa. Histologic examination showed that the buccal bone was composed of bundle and cortical bone. The thickness of the buccal bone was not uniform coronoapically, and the thinnest area of buccal bone was the coronal portion.

Objectives: The purpose of this study was to evaluate the osseointegration of the dental implants placed into the mandible augmented with different techniques in pigs., Material and Methods: Four adult domestic pigs were used. Horizontal augmentation of the mandible was performed in animals by using vascularized femur flap (VFF), non-vascularized femur graft (NVFG) and monocortical mandibular block graft (MG). After 5 months of healing 10 dental implants were placed into each augmented site. The pigs were sacrificed after 3 months of healing. Undecalcified sections were prepared for histomorphometric analysis., Results: Mean bone-implant contact (BIC) values for implants placed into MG, NVFG and VFF were 57.38 ± 11.97%, 76.5 ± 7.88%, 76.53 ± 8.15%, respectively. The BIC values of NVFG and VFF group were significantly greater than MG group (P<0.001). On the other hand, there was not statistically significant difference between NVFG group and VFF group (P=0.999)., Conclusion: NVFG as well as VFF can be considered as a promising method for augmentation of alveolar defects and the placement of the implants. The selection of non-vascularized graft or vascularized flap depends on the condition of the recipient site., (© 2010 John Wiley & Sons A/S.)

Distraction osteogenesis using the maximal osteogenic potential of the periosteum is introduced and demonstrated in 2 clinical cases. This technique includes minimizing cuts to and reflection of the periosteum on a transport segment; repositioning and suturing the cut periosteum to cover an osteotomy line, which becomes the distraction gap; and fixing an internal distraction device supraperiosteally. The cases involve reconstruction of a segmental defect of the mandible due to a recurrent ameloblastoma. A 51 + 58-mm posterior body and ramus and a 41 + 33-mm anterior body are reconstructed through 2-step and bilateral distraction osteogenesis, respectively. These cases proved the feasibility of the concept of the supraperiosteal transport distraction osteogenesis., (Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

We have shown that ischaemic preconditioning ameliorates both the local periosteal and the systemic leukocyte activation evoked by limb ischaemia-reperfusion. We hypothesized that the activation of chemosensitive afferent nerves by transient ischaemia contributes to the protective mechanisms of ischaemic preconditioning via a calcitonin gene-related peptide (CGRP)-dependent mechanism. In Sprague-Dawley rats, 60-min complete limb ischaemia was followed by 180 min of reperfusion. In further experiments, the CGRP analogue hCGRP (0.3 μg kg(-1)) or ischaemic preconditioning (2 × 10-min ischaemia/10-min reperfusion) was applied prior to the ischaemia-reperfusion insult. Ischaemic preconditioning was performed in three subgroups in which animals received the CGRP receptor antagonist CGRP(8-37) (30 μg kg(-1) h(-1)), the chemosensitive afferent nerve inactivator resiniferatoxin (3 × 15 μg kg(-1), sc), or vehicle. The effects of CGRP(8-37) and resiniferatoxin on ischaemia-reperfusion without ischaemic preconditioning were also evaluated. In the tibial periosteum of rats, intravital fluorescence microscopy and immunohistochemistry revealed significant attenuations of ischaemia-reperfusion-induced post-ischaemic leukocyte-endothelial interactions (rolling and adherence in the postcapillary venules) and tissue intracellular adhesion molecule expression following ischaemic preconditioning or hCGRP administration. Administration of CGRP(8-37) or pretreatment of animals with resiniferatoxin reversed the anti-inflammatory effects of limb ischaemic preconditioning, but failed to affect the microcirculatory consequences of ischaemia-reperfusion without ischaemic preconditioning. The results suggest that activation of the chemo- (capsaicin-) sensitive afferent nerves is involved in the mechanisms of microcirculatory anti-inflammatory protection provided by limb ischaemic preconditioning. Controlled activation of chemosensitive C-fibres or the CGRP receptors by the induction of ischaemic preconditioning or other means may furnish therapeutic benefit by ameliorating the periosteal microcirculatory consequences of tourniquet ischaemia.

Aims: Transient ischemia of osteoporotic bones during elective orthopedic surgery or fracture repair carries risks for serious complications, and estrogen loss or replacement has a potential to influence ischemia-reperfusion-induced inflammatory activation. To clarify this, we investigated the periosteal inflammatory changes in a clinically relevant time frame in ovariectomized rats, an experimental model of postmenopausal bone loss. Furthermore, the effects of chronic estrogen supplementation on the postischemic local and systemic inflammatory reactions were assessed., Main Methods: Bilateral ovariectomy or sham operation was performed in 3-month-old female Sprague-Dawley rats. Five months later, estrogen replacement therapy with 17β-estradiol (20 μg(-1) kg(-1) day(-1)) or vehicle treatment was initiated. The microcirculatory inflammatory consequences of 60-min total hindlimb ischemia followed by 180-min reperfusion were examined 11 months after ovariectomy and were compared with those in 3-month-old animals., Key Findings: The osteoporosis that developed 5 months after ovariectomy was significantly ameliorated by estrogen replacement therapy. Both in ovariectomized and in non-ovariectomized animals, ischemia-reperfusion elevated the neutrophil adherence ~3-fold in the postcapillary venules of the periosteum (intravital microscopy), with an ~50-60% increase in intravascular neutrophil activation (CD11b; FACS analysis), an enhanced TNF-α release (ELISA) and periosteal expression of ICAM-1 (the endothelial ligand of CD11b; immunohistochemistry). Exogenous 17β-estradiol considerably reduced TNF-α release and the number of neutrophil-endothelial interactions in the periosteum, without affecting the CD11b and ICAM-1 expression changes., Significance: Osteoporosis itself does not increase the magnitude of the limb ischemia-reperfusion-associated periosteal inflammatory reaction. Chronic estrogen supplementation, however, reverses osteoporosis and significantly ameliorates the microcirculatory consequences of transient ischemia., (Copyright © 2010. Published by Elsevier Inc.)