Calvarial Periosteum Research Articles

Oxytocin Receptors on Calvarial Periosteal Innervation: Therapeutic Target for Post-Traumatic Headache?

Following a mild traumatic brain injury (mTBI), the most prevalent and profoundly debilitating occurrence is the emergence of an acute and persistent post-traumatic headache (PTH), for which there are presently no approved treatments. A crucial gap in knowledge exists regarding the consequences of an mTBI, which could serve as a foundation for the development of therapeutic approaches. The activation of trigeminal sensory nerve terminals that innervate the calvarial periosteum (CP)-a densely innervated tissue layer covering the calvarial skull-has been implicated in both migraines and PTHs. We have previously shown that trigeminal oxytocin receptors (OTRs) may provide a therapeutic target for PTHs. This study examined the expression of oxytocin receptors on trigeminal nerves innervating the periosteum and whether these receptors might serve as a therapeutic target for PTHs using a direct application of oxytocin to the periosteum in a rodent model of PTH. We used retrograde tracing and immunohistochemistry to determine if trigeminal ganglion (TG) neurons innervating the periosteum expressed OTRs and/or CGRPs. To model the impact of local inflammation that occurs following an mTBI, we applied chemical inflammatory mediators directly to the CP and assessed for changes in immediate-early gene expression as an indication of neuronal activation. We also determined whether mTBI would lead to expression changes to OTR levels. To determine whether these OTRs could be a viable therapeutic target, we assessed the impact of oxytocin injections into the CP in a mouse model of PTH-induced periorbital allodynia. The results of these experiments demonstrate the following: (1) the cell bodies of CP afferents reside in the TG and express both OTRs and CGRPs; (2) inflammatory chemical stimulation of the periosteum leads to rapid activation of TG neurons (phospho-ERK (p-ERK) expression), (3) mTBI-induced inflammation increased OTR expression compared to the sham group; and (4) administration of oxytocin into the periosteum on day 2 and day 40 blocked cutaneous allodynia for up to one hour post-administration for both acute and persistence phases in the PTH model-an effect that was preventable by the administration of an OTR antagonist. Taken together, our observations suggest that periosteal trigeminal afferents contribute to post-TBI craniofacial pain, and that periosteum tissue can be used as a potential local target for therapeutics such as oxytocin.

Approximation of extracted features enabling 3D design tuning for reproducing the mechanical behaviour of biological soft tissues.

This article describes a new method, inspired by machine learning, to mimic the mechanical behaviour of target biological soft tissues with 3D printed materials. The principle is to optimise the structure of a 3D printed composite consisting of a geometrically tunable fibre embedded in a soft matrix. Physiological features are extracted from experimental stress-strain curves of several biological soft tissues. Then, using a cubic Bézier curve as the composite inner fibre, we optimised its geometric parameters, amplitude and height, to generate a specimen that exhibits a stress-strain curve in accordance with the extracted features of tensile tests. From this first phase, we created a database of specimen geometries that can be used to reproduce a wide variety of biological soft tissues. We applied this process to two soft tissues with very different behaviours: the mandibular periosteum and the calvarial periosteum. The results show that our method can successfully reproduce the mechanical behaviour of these tissues. This highlights the versatility of this approach and demonstrates that it can be extended to mimic various biological soft tissues.

Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway.

The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects. The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site. However, the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of pro-osteogenic factors. In this study, a poly (l-lactic acid) (PLLA)/hyaluronic acid (HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique. The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers (PLLA/HA@Irisin) achieved its sustained release. In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was improved by PLLA/HA@Irisin, as evidenced by a significant increase in alkaline phosphatase activity and matrix mineralization. Mechanistically, PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway. To assess the therapeutic effectiveness, PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats. The results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation, as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels. The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum, showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.

Alendronate reduces periosteal microperfusion in vivo

ObjectivesBisphosphonates are known to induce a severe adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). Previous studies have proven the impact of bisphosphonates on microperfusion; therefore, this study aimed to investigate alendronate-induced microcirculatory reactions in the calvarial periosteum of rats. Study designBone chambers were implanted into 48 Lewis rats. Microhemodynamics, inflammatory parameters, functional capillary density and defect healing were examined after alendronate treatment for two and six weeks using repetitive intravital fluorescence microscopy for two weeks. ResultsMicrohemodynamics remained unchanged. In alendronate-treated rats, inflammation was slightly increased, functional capillary density was significantly reduced (day 10: controls 100.45 ± 5.38 cm/cm2, two weeks alendronate treatment 44.77 ± 3.55 cm/cm2, six weeks alendronate treatment 27.54 ± 2.23 cm/cm2) and defect healing was decelerated. The changes in functional capillary density and defect healing were dose-dependent. ConclusionThe bisphosphonate alendronate has a significant negative impact on periosteal microperfusion in vivo. This could be a promising target for the treatment of MRONJ.

OnabotulinumtoxinA alters inflammatory gene expression and immune cells in chronic headache patients.

Occipital headache, the perception of pain in the back of the head, is commonly described by patients diagnosed with migraine, tension-type headache, and occipital neuralgia. The greater and lesser occipital nerves play central role in the pathophysiology of occipital headache. In the clinical setup, such headaches are often treated with onabotulinumtoxinA, a neurotoxin capable of disrupting ability of nociceptors to get activated and/or release proinflammatory neuropeptides. Attempting to understand better onabotulinumtoxinA mechanism of action in reducing headache frequency, we sought to determine its effects on expression of inflammatory genes in injected occipital tissues.To achieve this goal, we injected 40 units of onabotulinumtoxinA into four muscle groups (occipitalis, splenius capitis, semispinalis capitis, and trapezius muscles—all located on one side of the occiput) of patients with chronic bilateral occipital headache scheduled for occipital nerve decompression surgery 1 month later. At the time of surgery, we collected discarded muscle, fascia and periosteum tissues from respective locations on both sides of the neck and occiput and performed targeted transcriptome analyses to determine expression level of inflammatory genes in onabotulinumtoxinA-injected and onabotulinumA-uninjected tissues.We found that (i) onabotulinumtoxinA alters expression of inflammatory genes largely in periosteum, minimally in muscle and not at all in fascia; (ii) expression of inflammatory genes in uninjected periosteum and muscle is significantly higher in historical onabotulinumA responders than historical non-responders; (iii) in historical responders’ periosteum, onabotulinumA decreases expression of nearly all significantly altered genes, gene sets that define well recognized inflammatory pathways (e.g. pathways involved in adaptive/innate immune response, lymphocyte activation, and cytokine, chemokine, NF-kB, TNF and interferon signalling), and abundance of 12 different immune cell classes (e.g. neutrophils, macrophages, cytotoxic T-, NK-, Th1-, B- and dendritic-cells), whereas in historical non-responders it increases gene expression but to a level that is nearly identical to the level observed in the uninjected periosteum and muscle of historical responders; and surprisingly (iv) that the anti-inflammatory effects of onabotulinumA are far less apparent in muscles and absent in fascia.These findings suggest that in historical responders’ periosteum—but not muscle or fascia—inflammation contributes to the pathophysiology of occipital headache, and that further consideration should be given to the possibility that onabotulinumA mechanism of action in migraine prevention could also be achieved through its ability to reduce pre-existing inflammation, likely through localized interaction that lead to reduction in abundance of immune cells in the calvarial periosteum.

Induced osteogenesis using biodegradable and titanium periosteal distractors

BackgroundNew bone formation can result from periosteal distraction. This is achieved through progressive uplifting of the periosteum by increasing the interface between it and the bone surface. ObjectiveThis study investigated the impact of gradual periosteal distraction using biodegradable materials and titanium distraction devices. Materials and methods20 rabbits were separated into 2 groups. Distraction devices were placed in all groups after reflecting the calvarial periosteum. The device was actuated following 7 days. Group 1 got titanium device and Hydroxyapatite HA with poly-l-lactide (PLLA) device was utilized in group 2. Five animals were sacrificed from each group following 4 and 6 weeks. Newly formed bone was histologically and radiographically assessed. ResultsThe histological observations showed that both distraction devices successfully induced osteogenesis and effectively distracted the soft tissue following 4 and six weeks. The study showed scattered bone trabeculae, with adipose tissue and multiple dome-shaped bones. Micro-computed tomography showed newly formed bone that was far less radiopaque than the initial basal bone. The connective tissue appeared as a radiolucent area that decreased gradually toward the fixation point of the device. At 6 weeks, the percentage of new bone was significantly higher than at 4 weeks for both devices. The PLLA device showed more bone than did the titanium device at both 4 and 6 weeks, but no significant difference was observed. ConclusionsBoth distraction devices were effective in distracting the periosteum and inducing new vascularized bone. The PLLA device induced more bone than the titanium device. Thus, the distractor composition may influence the new bone.

Enhanced bone formation onto the bone surface using a hydroxyapatite/collagen bone-like nanocomposite.

The process of bone formation onto the bone surface using a hydroxyapatite/collagen bone-like nanocomposite (HAp/Col) was investigated. Immersion tests were performed to evaluate the impact of pH on the degradation of the specimens in an aqueous environment. The specimens were soaked in aqueous solutions of pH 4.0, 5.0, and 7.0. Using standardized images, the top-view areas of the specimens were measured. Animal experiments were performed to investigate the bone formation process onto the bone surface. The specimens were placed under the rat calvarial periosteum, and μCT image analysis and histological observation were performed on samples harvested on postoperative Days 3, 5, and 7. In all experiments, β-tricalciumphosphate (β-TCP) was adopted as the control. HAp/Col turned to gel in acidic environments below pH 5.0. In contrast to the β-TCP, the HAp/Col specimens placed under the periosteum expanded and attained a hollow structure with a gel-filled center, accompanied by larger volume of new bone and appearance of TRAP-positive multinucleated cells on postoperative Day 5. Therefore, HAp/Col can enhance bone formation onto the bone surface via induction of TRAP-positive multinucleated cells, and may have clinical applications.

Stromal cell-derived factor-1 accelerates bone regeneration through multiple regenerative mechanisms

ObjectiveStem cell transplantation has become a popular and promising therapeutic approach for many clinical conditions. Engrafted mesenchymal stem cells (MSCs) can promote bone regeneration in both humans and model animals; however, the differentiation and survival rates of the engrafted MSCs are reported to be poor. We hypothesized that MSCs promote bone regeneration primarily through paracrine mechanisms. SDF-1 is a factor secreted from MSCs that is known to be involved in cell-recruitment and angiogenesis. In this study, we examined the bone-regenerating activity of SDF-1 in the rat calvarial bone defect model. MethodsCollagen sponge containing SDF-1 was transplanted into the rat calvarial bone defect. The effects of treatment were examined both histological and microcomputed tomography analysis. The effects of SDF-1 on cellular migration and proliferationin vitro were assessed by transwell and WST-assay, respectively. ResultsSDF-1 significantly enhanced the bone regeneration in rat calvarial bone defect model. SDF-1 promoted the recruitment of endogenous MSCs/osteogenic progenitors and promoted angiogenesisin vivo. Furthermore, SDF-1 directly enhanced the cell-migration activity of human bone marrow MSCs (hBMMSCs), human umbilical vein endothelial cells (HUVECs), and rat calvarial periosteum cells (rCPCs), without affecting their proliferative activities, in vitro. ConclusionsOur findings suggest that the local administration of SDF-1 enhances bone regeneration by inducing multiple endogenous tissue-regenerating activities.

Erratum to: A Novel Method of Neo-osseous Flap Prefabrication: Induction of Free Calvarial Periosteum with Bioactive Glass.

Erratum to: A Novel Method of Neo-osseous Flap Prefabrication: Induction of Free Calvarial Periosteum with Bioactive Glass.

In vivo visualisation of different modes of action of biological DMARDs inhibiting osteoclastic bone resorption

ObjectivesOsteoclasts play critical roles in inflammatory bone destruction. Precursor cell migration, cell differentiation, and functional cell activation are all in play. Biological disease-modifying antirheumatic drugs (DMARDs) have been shown to...

Preparation and Evaluation of Tibia- and Calvarium-Derived Decellularized Periosteum Scaffolds.

The periosteum plays a key role in bone regeneration and an artificial bionic material is urgently required. The periostea on the tibia and skull differ with respect to the types of cells, microstructure, and components, leading to different biological functions and biomechanical properties. We aimed to prepare decellularized periosteum scaffolds derived from different origins and evaluate their angiogenic and osteogenic activities. Histological assessment of α-smooth muscle actin, bone morphogenetic protein-2, and alkaline phosphatase in tibial and calvarial periosteum tissues provided preliminary information on their differing angiogenic and osteogenic properties. We developed decellularization protocols to completely remove the periosteum cellular components and for good maintenance of the hierarchical multilayer structures and components of the extracellular matrix (ECM) with no cytotoxicity. Moreover, using a chicken egg chorioallantoic membrane assay and a nude mouse implantation model, we found that tibia-derived periosteum ECM had superior osteogenic activity and calvarium-derived ECM had good angiogenic activity. The preliminary mechanisms of differing activities were then evaluated by osteogenesis- and angiogenesis-related gene expression in human umbilical vein endothelial cell- and MC-3T3 cell-seeded ECM scaffolds. Thus, this study provides periosteum biomaterials that are derived from specific tissues and have different functional properties and structures, for use in bone regeneration.

Management of Pediatric Atlantoaxial Rotatory Subluxation with a Simple Handmade Cervical Traction Device: Doing More with Less

To introduce a novel traction device for management of pediatric atlanto-axial rotatory subluxation (AARS) in source limiting areas. Atlanto-axial (C1-C2) joint is accountable for up to two third of total axial craniocervical rotation. Its major role in pivotal rotation of cervical spine makes it more vulnerable to a certain type of injury known as AARS. Management of AARS is based on the Fielding classification which includes closed reduction and immobilization and cervical fusion in unstable cases. There are several cervical traction devices including the Gardner-Wells tongs and halter traction device. All the available devices require insertion of pins into the calvarial periosteum which is a painful, invasive and intolerable procedure especially for the pediatric patients. We designed a simple hand-made cervical traction device which is composed of 2 soft padded straps (40 × 4 cm) and 2 connecting strings which can be applied easily under the chin and occipital areas of the patients. We successfully treated a 9-year-old girl with AARS with the device. The advantage of the device is its available, inexpensive and non-invasive and the patient might tolerate it more easily compared to the previously designed instruments. This hand-made simple cervical traction device in source limiting centers and hospitals is a good example of doing more with less. It was effective and the tolerance of the patient was acceptable. Further studies with larger series are required for providing appropriate evidence.

A Novel Method of Neo-osseous Flap Prefabrication: Induction of Free Calvarial Periosteum with Bioactive Glass.

Reconstruction of craniofacial bone defects is a primary focus of craniofacial surgery. Although autogenous bone grafts remain as the gold standard, alloplastic materials have also gained widespread popularity due to their off-the-shelf availability, ease of use, and durability. In addition to replacing the missing bone, some of these alloplastic materials have also been found to induce new bone formation. In this study, the phenomenon of neo-osseous induction with bioactive glass was investigated for different implant-soft tissue configurations. Thirty-two male, Wistar albino rats were divided into four equally numbered study groups. In group 1 (FP), adipofascial groin flaps were prefabricated with free periosteal grafts. In group 2 (FPB), adipofascial groin flaps were prefabricated with free periosteal grafts and bioactive glass. In group 3 (FB), adipofascial groin flaps were prefabricated with bioactive glass. In group 4 (control), adipofascial groin flaps were not prefabricated. Morphometric analyses of the prefabricated structures were performed using micro-CT. The histologic properties of the ectopic ossification were assessed by using a modified scoring system. Group 1 (FP) showed the greatest rate of mature lamellar bone formation. Group 2 (FBP) showed the greatest amount of bone density and volume. However, the addition of bioactive glass in group 2 (FBP) decreased the rate of mature lamellar bone formation when compared with group 1 (FP). Ectopic ossification was not observed in the control group. Bioactive glass can be successfully used in the prefabrication of vascularized compound structures for the reconstruction of complex bone defects. However, interference with the periosteal induction of mature lamellar bone formation should be taken into consideration, especially in pediatric bone defects, which primarily rely on spontaneous osteogenesis through periosteal induction.

Anchoring structure of the calvarial periosteum revealed by focused ion beam/scanning electron microscope tomography.

An important consideration in regeneration therapy is the fact that the tissue surrounding an organ supports its function. Understanding the structure of the periosteum can contribute to more effective bone regeneration therapy. As a cellular source, the periosteum also assists bone growth and fracture healing; this further necessitates its direct contact with the bone. However, its anchoring strength appears to be inexplicably stronger than expected. In this study, we used focused ion beam/scanning electron microscope tomography to investigate ultrathin serial sections as well as the three dimensional ultrastructure of the periosteum to clarify the architecture of its anchoring strength, as such assessments are challenging using conventional methods. We discovered perforating fibres that arise from the bone surface at 30 degree angles. Additionally, the fibres across the osteoblast layer were frequently interconnected to form a net-like structure. Fibroblast processes were observed extending into the perforating fibres; their morphologies were distinct from those of typical fibroblasts. Thus, our study revealed novel ultrastructures of the periosteum that support anchorage and serve as a cellular source as well as a mechanical stress transmitter.

Mild closed head injury promotes a selective trigeminal hypernociception: implications for the acute emergence of post-traumatic headache.

Headache is one of the most common symptoms following traumatic head injury. The mechanisms underlying the emergence of such post-traumatic headache (PTH) remain unknown but may be related to injury of deep cranial tissues or damage to central pain processing pathways, as a result of brain injury. A mild closed head injury in mice combined with the administration of cranial or hindpaw formalin tests was used to examine post-traumatic changes in the nociceptive processing from deep cranial tissues or the hindpaw. Histological analysis was used to examine post-traumatic pro-inflammatory changes in the calvarial periosteum, a deep cranial tissue. At 48 h after head injury, mice demonstrated enhanced nociceptive responses following injection of formalin into the calvarial periosteum, a deep cranial tissue, but no facilitation of the nociceptive responses following injection of formalin into an extracranial tissue, the hindpaw. Mice also showed an increase in the number of activated periosteal mast cells 48 h following mild head trauma, suggesting an inflammatory response. Our study demonstrates that mild closed head injury is associated with enhanced processing of nociceptive information emanating from trigeminal-innervated deep cranial tissues, but not from non-cranial tissues. Based on these finding as well as the demonstration of head injury-evoked degranulation of calvarial periosteal mast cells, we propose that inflammatory-evoked enhancement of peripheral cranial nociception, rather than changes in supraspinal pain mechanisms play a role in the initial emergence of PTH. Peripheral targeting of nociceptors that innervate the calvaria may be used to ameliorate PTH pain.

The sensory innervation of the calvarial periosteum is nociceptive and contributes to headache-like behavior

Headaches are thought to result from the activation and sensitization of nociceptors that innervate deep cephalic tissues. A large body of evidence supports the view that some types of headaches originate intracranially, from activation of sensory neurons that innervate the cranial meninges. However, the notion of an extracranial origin of headaches continues to be entertained, although the identity of deep extracranial cephalic tissues that might contribute to headaches remains elusive. Here we employed anatomical, electrophysiological, and behavioral approaches in rats to test the hypothesis that the sensory innervation of the calvarial periosteum is nociceptive. Neural tracing indicated that the calvarial periosteum overlying the frontal and parietal bones is innervated primarily by small and medium-sized neurons in the trigeminal ganglion’s ophthalmic division. In vivo single-unit recording in the trigeminal ganglion revealed that calvarial periosteal afferents have slowly conducting axons, are mechanosensitive, and respond to inflammatory mediators, consistent with a nociceptive function. Two distinct neuronal populations were distinguished based on their peripheral axonal trajectory: one that reached the periosteum through extracranial branches of the trigeminal nerve, and another that took an intracranial trajectory, innervating the cranial dura and apparently reaching the periosteum via the calvarial sutures. In behavioral studies, inflammatory stimulation of these afferents promoted periorbital tactile hypersensitivity, a sensory change linked to primary headaches. Activation and sensitization of calvarial periosteal afferents could play a role in mediating primary headaches of extracranial and perhaps also intracranial origin, as well as secondary headaches such as postcraniotomy and posttraumatic headaches. Targeting calvarial periosteal afferents may be effective in ameliorating these headaches.

Osteoblastic Differentiation and Mineralization Ability of Periosteum-Derived Cells Compared With Bone Marrow and Calvaria-Derived Cells

Clinically, bone marrow stromal cells (BMCs) are the most common source of osteoprogenitor cells. Its harvest process, however, is invasive to patients. Previous reports have shown the potential advantages of using periosteum-derived cells (PDCs) as a source of cell-based transplant therapy. The objective of our study was to characterize the osteoblastic differentiation and mineralization ability of PDCs versus BMCs and osteoblasts (OBs). BMCs, OBs, and PDCs were isolated from 4-week-old male Wistar rats. To characterize the differentiation ability of the cells, MTS assay, alkaline phosphatase (ALP) activity staining, picrosirius red staining, and alizarin red staining were performed. Immunohistochemistry was performed on paraffin sections of calvarial periosteum to determine the presence of mesenchymal stem cells. PDCs showed the greatest proliferation rate compared with BMCs and OBs. Matured collagenous matrix formation was observed in PDCs and BMCs. ALP-positive cells and in vitro mineralization were evident in all cell types analyzed; however, that of PDCs was not comparable to that of the OBs and BMCs. Immunohistochemistry revealed the presence of STRO-1-and CD105-positive cells in the cambium layer of the periosteum. PDCs have remarkable proliferative ability, but contain only a small population of osteogenic cells compared with BMCs and OBs. Although cell activity can be affected by various factors, such as age, culture condition, additives, and so forth, PDCs are likely not the source of OBs, although they might provide matrices that indirectly aid in bone formation.

Experience of ReCell in Skin Cancer Reconstruction

The ReCell system (Avita Medical) is a cell culture product that allows the immediate processing of a small split-thickness skin biopsy to produce a complete population of cells including keratinocytes, melanocytes, Langerhans cells and fibroblasts. This series is the first to highlight the reconstructive applications of ReCell following ablative skin cancer surgery. The ReCell system was utilized for three patients following skin cancer excision. In two cases, the cells were applied to forehead flap donor sites following nasal reconstruction. In one case, the cells were applied to the calvarial periosteum following wide local excision of a melanoma scar. Assessment of the treated area was performed using the patient and observer scar assessment scale after 1 year. The Patient and Observer Scar Assessment Scale (POSAS) scores for the 2 patients treated with ReCell following forehead flap surgery were 22 and 32. The score for the patient that underwent wide local excision of a melanoma scar was 45. The absence of a donor site, accelerated healing and the satisfactory aesthetic appearance of the mature scars in this series suggest that ReCell may play a useful role in reconstruction following skin cancer excision.

Bone Augmentation Using Novel Unidirectional Porous Hydroxyapatite with Bone Morphogenetic Protein-2 on Rat Skull

Unidirectional porous hydroxyapatite (UDPHAp) is a material whose microstructure consists of cross- sectional oval pores with a pore diameter in the range of 100-300 m that penetrate through the material. UDPHAp has proven suitable for osteogenesis and angiogenesis. The present study was designed to evaluate the osteogenic effect of a newly developed UDPHAp as a carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat onlay graft model. UDPHAp was implanted beneath the calvarial periosteum of rats to simulate alveolar bone augmentation in a clinical condition. At 2 weeks after implantation, UDPHAp with rhBMP-2 resulted in active bone formation, and the augmented bone was connected directly with the original bone, whereas commercialized porous hydroxyapatite (PHAp) with rhBMP-2 showed little bone formation. These results suggest that UDPHAp in this model is suitable for onlay graft and is an effective biomaterial for the rhBMP-2 delivery system.

Induced Osteogenesis Using a New Periosteal Distractor

We developed a new device mainly composed of a titanium mesh to distract the periosteum. The purpose of this study is to evaluate induced osteogenesis by periosteal distraction with the new device. We divided 12 Japanese male rabbits into 3 groups, with 4 rabbits in each. In all groups the calvarial periosteum was reflected, and 1 side of the titanium mesh was fixed to the bone surface with 2 micro-screws. In groups 1 and 2, an elevation screw was inserted into a serrated hole on the other side of the plate 7 days after surgery. Then the device was activated at a rate of 0.5 mm every 12 hours for 5 days. At 4 weeks of the consolidation period, group 1 was killed, followed by group 2 at 6 weeks. Group 3 (control) received no screws, and hence no activation was performed. In group 3, 2 animals were killed 4 weeks after titanium mesh insertion, followed by the other 2 animals at 6 weeks. The device was designed to simultaneously distract the periosteum at different rates along its inclined surface. Newly formed bone was histologically and radiographically evaluated. The new device effectively induced osteogenesis and successfully distracted the soft tissue after 6 weeks in a rabbit model. The new device is slim, and the procedure is straightforward. Thus, periosteal distraction with this device can potentially be used for vertical and horizontal ridge augmentation in the oral cavity. In addition, the results suggest that connective tissue growth in the distraction site might be controlled by reducing the speed of periosteal distraction.