Calvarial Graft Research Articles

Split calvarial bone graft for the reconstruction of skull defects

Cranioplasty is a common, but formidable surgical procedure for neurosurgeons, in patients with scalp and / or calvarial defects. This procedure can be simple or complex. The main objectives of cranioplasty are: To achieve primary wound healing, obliterate dead space, and seal off sterile cranial areas from contaminated oronasal cavities, to restore the normal barriers protecting the intracranial structures (together with a satisfactory cosmetic result) and obtain a permanent or very durable reconstruction, using biologically inert materials, and also to restore the aesthetics. The greatest problem is selecting the optimum material for repair of the cranial defect. Many synthetic substitutions of the dura and bone are often used for reconstruction of the skull base; unfortunately, these methods bear significant disadvantages and can induce chronic inflammation, carry a high risk of infection, and are inferior to biological sources in terms of strength and sealing quality [with the exception of some materials, such as titanium mashes and CortossTM (Orthovita®, Malvern, USA), which are seen to have more strength than the thin split thickness calvarial bone]. The primary aim of this article is to review the basic principles to use the split calvarial graft for the reconstruction of the skull defect.

Spectrum of primary bone grafting in cranio maxillofacial trauma at a tertiary care centre in India

Background:In past several years, traumas following road traffic accidents and other causes have increased, owing to an increase in mechanization and pace of life. These patients frequently have complicated injuries involving soft tissue and the craniofacial skeleton. Assessment of bony injuries and loss of portions of facial skeleton and their management has proved to be a challenge to the reconstructive surgeon.Aims:Primary bone grafting of craniofacial skeletal injuries provides an opportunity for one stage correction of bony defects. The varied spectrum of primary bone grafts for management of craniomaxillofacial injuries are evaluated in this study.Materials and Methods:Patients with a history of acute trauma resulting in facial skeletal injuries with or without bone loss were included in the study. Primary bone grafting was undertaken in situations requiring contour correction, replacement of skeletal losses and for rigid fixation of fracture segments. Olecranon, Iliac crest, ribs, Vascularized as well as nonvascularized outer table calvarial grafts and nonvascularized inner table calvarial grafts were used in this study.Results:Sixty two patients of craniomaxillofacial injury following trauma requiring primary bone grafting were considered in this study. Fifty seven percent of patients (n=32) required primary bone grafting for replacement of bone loss while bone grafting for contour correction was done in twenty three patients. The parietal calvaria overlying the non-dominant hemisphere was used as a source of bone graft in forty-nine patients. Nearly ninety-two percent of the patients were satisfied with the results of primary bone grafting.Conclusions:Functional and aesthetic assessment of each of these patients, managed with primary bone grafting revealed a low rate of disabilities and high percentage of satisfaction in this study.

Reply

Sir: In response to the letter entitled “Onlay Bone Autografts in Nasal Augmentation: Ileum versus Calvaria,” we would like to review some of the advantages and disadvantages associated with the use of iliac crest and calvarial bone for augmentation rhinoplasty. The use of iliac crest and calvarial bone grafts has been described in the literature. Some recent studies show satisfactory cosmetic and functional results with a low incidence of donor-site morbidity.1–4 However, it is important to note that most studies show that calvarial bone (membranous) retains its size and form to a significantly greater extent than those of endochondral origin such as ilium, both as an inlay and as an onlay.5–8 This remained true with or without the application of guided bone regeneration.9 With regard to donor-site morbidity, some studies show that iliac crest harvesting leads to moderate morbidity, with complications including fracture, gait disturbance, persistent pain, hernias, fat embolism, and sensory disturbance,10–12 although other studies claim acceptable aesthetic results with no long-term sequelae.11,13 Reviews of the literature have shown severe complications to be rare but certainly worth considering when determining donor sites.14 Calvarial bone grafts are typically obtained by means of split harvesting from the temporoparietal region. This technique has been shown to be tolerated by patients, with minimal or no postoperative discomfort. Severe complications are exceedingly rare with split calvarial grafts but include dural and central nervous system injury and hematoma and are more likely with full-thickness harvests.15 Autologous cartilage grafts (of septal and auricular type) remain the preferred grafts for rhinoplasty and nasal reconstruction.15–17 Split calvarial bone has emerged as a preferred bone graft in the recent nasal reconstruction literature because of its superior strength, lower resorption rate, and lower donor-site morbidity. However, each patient and reconstructive situation must be considered individually, with the advantages and disadvantages of each graft and harvest risks kept in mind. Ali Sajjadian, M.D. Nima Naghshineh, M.D., M.Sc. Roee Rubinstein, M.D. Newport Beach, Calif.

DCE-MRI to Evaluate Vascularization in Calvarial Grafts

DCE-MRI to Evaluate Vascularization in Calvarial Grafts

Split Calvarial Graft to Repair the Large Frontal Bone Defect

The ideal reconstructive material for cranioplasty is autogenous bone, however if it is not available the use of alloplastic materials is recommended. We present a case of 26-year-male patient who sustained compound depressed fracture of the frontal bone and associated anterior cranial fossa fracture following a road traffic accident. He was managed at hospital where the fractured bone fragments were removed but recently presented with watery discharge from nose (CSF rhinorrhoea) and cosmetic deformity of forehead. We describe the utilization of autogenous local frontal bone split calvarial graft for the reconstruction of the defect.

Middle Fossa Approach to a Temporosphenoidal Encephalocele -Technical Note-

Temporosphenoidal encephalocele (TSE) is a rare entity caused by herniation of the anteromedial temporal lobe into the sphenoid sinus (SS) through a middle fossa (MF) defect. A 45-year-old woman presented with a spontaneous TSE manifesting as a 4-year history of recurrent cerebrospinal fluid rhinorrhea and meningitis. Coronal computed tomography showed a skull defect in the superior wall of the right lateral recess of the SS. This homogeneous intrasphenoidal lesion appeared hypointense on T(1)-weighted magnetic resonance (MR) imaging and hyperintense on T(2)-weighted MR imaging. The patient underwent a frontotemporal craniotomy and extradural MF exploration. The encephalocele was amputated and the temporal base dura primarily sutured and reinforced with fat graft. The MF hole was plugged with temporalis fascia and a calvarial graft layered over the bone defect. Histological examination confirmed meningoencephalocele. Rhinorrhea resolved and the patient remained asymptomatic. Resection of an anteromedial TSE and closure of the craniodural defect in the MF floor via a less invasive extradural skull base approach is effective.

Immunohistochemical, tomographic and histological study on onlay bone graft remodeling. Part II: calvarial bone

Little information is available on the molecular events that occur during graft incorporation over time. The calvarial bone (Cb) grafts have been reported to produce greater responses compared with other donor regions in maxillofacial reconstructions, but the scientific evidences for this are still lacking. The objectives of this study are (1) to study the morphological pattern of Cb onlay bone grafts and compare them with the biological events through immunohistochemical responses and (2) to establish the effects of perforations in maintaining the volume and bone density of the receptor bed. Sixty New Zealand White rabbits were submitted to Cb onlay bone grafts on the mandible. In 30 rabbits, the receptor bed was perforated (perforated group), while for the remaining animals the bed was kept intact (non-perforated group). Six animals from each group were sacrificed at 5, 7, 10, 20 and 60 days after surgery. Histological sections from the grafted area were prepared for immunohistochemical and histological analyses. Immuno-labeling was found for proteins Osteoprotegerin (OPG), receptor activator of nuclear factor-kappabeta ligand (RANKL), alkaline phosphatase (ALP), osteopontin (OPN), vascular endothelial growth factor (VEGF), tartrate-resistant acid phosphatase (TRAP), Type I collagen (COL I) and osteocalcin (OC). The tomography examination [computerized tomography (CT) scan] was conducted just after surgery and at the sacrifice. The histological findings revealed that the perforations contributed to higher bone deposition during the initial stages at the graft-receptor bed interface, accelerating the graft incorporation process. The results of the CT scan showed lower resorption for the perforated group (P<or=0.05), and both groups showed high bone density rates at 60 days. This set of evidences is corroborated by the immunohistochemical outcomes indicating that proteins associated with revascularization and osteogenesis (VEGF, OPN, TRAP and ALP) were found in higher levels in the perforated group. These findings indicate that the bone volume of calvarial grafts is better maintained when the receptor bed is perforated, probably resulting from more effective graft revascularization and greater bone deposition. The process of bone resorption peaked between 20 and 60 days post-operatively in both groups although significantly less in the perforated group.

Options in orbital floor reconstruction in blowout fractures: a review of ten cases

The purpose of this case series was to assess the aesthetic and functional outcome of orbital floor reconstruction performed with calvarial bone graft, titanium mesh or prolene mesh. Ten cases of orbital blowout fractures treated at our centre from October 2006 to July 2008 were considered for this study. Clinical examination, patient satisfaction and radiographic investigations were used to assess repaired fractures. Prolene mesh was used in four cases, titanium mesh was used in four cases and calvarial graft used in two cases. Nine patients had significant improvement in their esthetic appearance. Symmetry was restored in all cases. All ten cases had a noticeable improvement in the function. Of total ten cases six had diplopia, three recovered completely during the six months after the surgery. Three cases showed improvement later. All ten cases with enopthalmos recovered completely. Of the nine patients with infraorbital numbness, all recovered completely during the six months following surgery. One patient where the reconstruction was done with calvarial bone graft showed mild discrepancy in the ocular level. For small, linear defects measuring less than 2cm with enopthalmos and restricted ocular movements, prolene mesh (four cases) was used. For larger defects and impure blowout fractures involving the infraorbital rim, calvarial graft (two cases) or titanium mesh (four cases) was used. The outcome of surgery with all three materials was satisfactory. No postoperative complications were seen except for mild hypoglobus in a case reconstructed with calvarial graft. All three materials, calvarial graft, titanium mesh, prolene mesh, have the potential to be useful reconstructive materials in orbital floor blowout fractures.

One-stage reconstruction using a vascularized calvarial flap for intractable scalp ulcers in relation with cranial implants without removing the whole prosthesis

When alloplastic cranial implants present some complications, the classical strategy has been to remove them. Removal of the custom-made artificial skull, however, requires a second cranioplasty. We describe two representative cases of intractable scalp ulcer over the cranial prosthesis treated by vascularized calvarial flap without totally removing the implant. One patient had a previous ceramic implantation and the other a large titanium mesh, whose precedent local skin flap methods to treat the scalp ulcer were not successful. After the implant beneath the scalp ulcer was partially removed, a vascularized calvarial flap was raised. The calvarial graft of the flap was utilized to repair the implant defect and the galeal part of the flap was utilized to patch the ulcer from the reverse side. The clinical outcome is excellent. Our experience clearly demonstrated that the vascularized calvarial flap contributes to maintain a sufficient blood supply for the calvarial graft, reduces the risk of infection and provides a new tissue bed for the healing of a skin ulcer over a cranial implant for this difficult-to-treat cranial reconstruction.

Demineralized Bone Matrix and Resorbable Mesh Bilaminate Cranioplasty: A Novel Method for Reconstruction of Large-Scale Defects in the Pediatric Calvaria

Pediatric patients with large-scale calvarial defects often lose the osteogenic potential of their dura before developing a diploic space sufficient to facilitate harvest of split-thickness calvarial grafts. The authors present their experience using demineralized bone matrix and resorbable mesh bilaminate for the repair of large-scale cranial defects in pediatric patients. A retrospective review of the Cleft-Craniofacial Center database at Children's Hospital of Pittsburgh was performed from 2003 through 2007. Patients who underwent cranioplasties using demineralized bone matrix and resorbable mesh bilaminate were identified. Indications, defect size, quantity of demineralized bone matrix used, complications, follow-up, and computed tomographic scans were reviewed. Eleven patients underwent 13 skull reconstructions using demineralized bone matrix and resorbable mesh bilaminate cranioplasty. Mean age was 3.6 years (range, 2.1 to 4.9 years); average defect size was 30.8 cm (range, 6.6 to 80.0 cm). Mean clinical follow-up was 29.3 months (range, 13.4 to 41.8 months). All patients had follow-up computed tomographic scans. The average time of follow-up scan was 18.7 months postoperatively (range, 6.9 to 32.6 months). Seven patients had immediate postoperative scans in addition to long-term follow-up scans, facilitating the calculation of a 98 percent average defect healing (range, 95 to 100 percent). All patients had clinically stable cranial reconstructions at follow-up. When autogenous bone is not available, demineralized bone matrix and resorbable mesh bilaminate cranioplasty is an alternative method of calvarial reconstruction when used in a healthy site free of scarring or infection. This cranioplasty technique has provided consistent bony regeneration, with no donor-site morbidity.

The Arrhinias

The Arrhinias consist of three groups of malformations: the Total Arrhinias (T-AR), the Hemi-Arrhinias (H-AR, often called Hemi-Nasal Ageneses) and the Proboscis Lateralis (P.L.) This work deals with 51 cases of Arrhinias gathered within 35 years (8 T-AR, 25 H-AR, and 18 P.L): their anatomy, clinical signs, and some indications for treatment; but it does not extend to a discussion for their etiopathology. However, the T-AR and the H-AR represent ageneses, whereas the P.L represents a dysgenesis. The anomalies common to the three groups of Arrhinias are many: the agenesis of the nasal bones, the telecanthus which is often in contrast to the hypo-telorbitism, the obstruction of the naso-lacrimal passage, the ectasia of the lacrimal sac with an erosion of the inferomedial angle of the orbit, the hypopneumatization of the maxillary sinus and a small maxilla, the unerrupted canines, the flattened fronto-nasal process, the obliteration of the cribriform plate, the dysplasia in the root of the eyebrows, the transverse hypoplasia of the upper lip, the frequency of microphthalmia, colobomas of the iris and nystagmus. Cleft lip and palate are frequently associated with the Arrhinias (see Table I) and also other facial malformations, but in different proportions, according to groups. They are: cryptophtalmias, eyelid coloboma, fronto-orbital encephalocele, agenesis of the premaxilla or prolabium, microtia. (See Table II) The basic principles of the treatment are the following: In the T-AR, a nasal passage should initially be bored through the maxilla, or there should be a displacement of the two halves of the mid-face by a procedure known as "facial bipartition". This nasal passage should be epithelialized and maintained wide open to the pharynx until the nasal construction. In the H-AR, it is sufficient to create an epithelialized passage through the curtain of bone where one would expect the pyriform rim to be and carry this passage through the septum into the contralateral nasal airway. Then, regardless of the type of arrhinia, the nasal construction is carried out with a forehead flap and bone grafts. The first grafts are either iliac or tibial, and subsequent ones are generally outer table calvarial grafts harvested from the parietal region. Later, there are further procedures: a maxillary advancement, a lengthening of the central midface, the final stages of the nasal construction, the elevation of the medial canthus, and the restoration of the infero-medial angle of the orbit (but rarely an efficient lacrimal drainage). The earliest stage for surgery can be debated. A strategy for treatment is suggested. Finally, 20 brief comments are made, which are as much questions asked concerning the three groups of arrhinia and their relationship with other centro-facial and latero-facial malformations.

Primary Ewing′s sarcoma of the frontal bone with intracranial extension

Primary Ewing's sarcoma arising from the skull is extremely rare. We report a case of an 11-year-old male child with primary Ewing's sarcoma of the frontal bone with intracranial extension. We also discuss the imaging and intraoperative findings and describe our use of a split calvarial graft in the present case.

BMP-2-Based Repair of Large-Scale Calvarial Defects in an Experimental Model

Pediatric craniofacial surgery is complicated by a shortage of autologous bone. Children between 2 and 10 years of age are especially problematic, as the dura has lost its potential to spontaneously heal large calvarial defects by approximately 2 years of age, and split calvarial grafts are often unavailable because of the underdeveloped diploic space until later childhood. We demonstrate the efficacy of a BMP-2-based system in repairing large-scale cranial defects in a rabbit model. Calvarial defects, 15 mm, were created in 18 adult New Zealand white rabbits, treated as follows: group 1, no repair (n = 6); group 2, absorbable collagen sponge (ACS) (n = 4); and group 3, recombinant human bone morphogenetic protein 2 delivered on ACS (rhBMP-2/ACS) (n = 8). Bone regeneration 6 weeks postoperatively was evaluated by 2- and 3-dimensional standard computed tomography, micro-computed tomography. Analysis of variance was performed using SPSS. The generated bone was also evaluated histologically. After 6 weeks, group 1 defects were on average 32.8% (SD, 8.8%) ossified. Group 2 defects were on average 34.4% (SD, 17.1%) ossified. Defects in group 3 were on average 96.9% (SD, 3.7%) ossified, significantly (P < 0.005) more than the defects in groups 1 and 2. rhBMP-2-induced bone was histologically and radiographically consistent with native bone. This study demonstrates the efficacy of rhBMP-2/ACS for the repair of calvarial defects in the rabbit model. rhBMP-2/ACS may offer a viable treatment option for craniofacial surgeons facing a shortage of bone, with the potential to replace autologous bone grafts and render their attendant morbidities obsolete.

Vascularized Calvarial Bone Flaps and Midface Reconstruction

After studying this article, the participant should be able to: 1. Identify the fascial layers of the temporalis region. 2. Understand the three-dimensional nature of the orbit and upper maxillectomy defects. 3. Understand the surgical harvest of temporalis flaps and temporoparietal flaps with vascularized bone. 4. Appreciate preoperative risk factors and postoperative complications. Although vascularized calvarial bone grafts were originally explored for use in reconstruction of midface hypoplasia defects, they offer significant value in application to oncologic reconstruction of the midface. A review of eight cases of midface reconstruction using vascularized calvarial grafts was performed to illustrate the versatility and dependability of these flaps. Adequate bony and soft-tissue contours were achieved with no clinical evidence of bone graft resorption. No immediate postoperative complications including infection and hematoma or seroma formation were noted. One patient experienced a delayed sinusitis from a blocked duct. The use of vascularized calvarial grafts supported by temporoparietal fascia, combined deep temporal fascia, and temporalis muscle provides excellent soft-tissue coverage and adequate bone stock for reconstruction of complex defects. Maintaining vascularization of the bone graft not only resists infection but also opposes resorption associated with nonvascularized grafts, particularly those in compromised wounds.

Catcher's mask cranioplasty for extensive cranial defects in children with an open head trauma: a novel application of partial cranioplasty

In children who have suffered a severe, extensive head trauma, cranioplasty is complicated because allografting is not advisable in pediatric patients and the amount of available autologous materials is limited. To overcome these problems, we employed a combination of autologous rib grafts and calvarial grafts for partial cranioplasty. We named this partial cranioplasty technique 'catcher's mask cranioplasty'. Rib grafts were placed mimicking a baseball catcher's mask to obtain maximum strong coverage of the defect. Calvarial grafts were used to achieve a smooth forehead contour. Islands of osteoanagenesis were also used. These autografts were of sufficient strength, esthetically satisfactory, and no patient developed sinking skin flap syndrome. Catcher's mask cranioplasty is a useful technique to successfully reconstruct the skull in pediatric patients with extensive cranial defects and an insufficient amount of autologous graft material.

Single-Stage Complex Reconstruction for Fibrous Dysplasia: A Case Report

Fibrous dysplasia is a benign skeletal condition which can involve the craniofacial skeleton. Surgery is indicated for correction of deformity and neurovascular decompression. Traditional surgery involves harvesting remote bone or calvarial grafts, requiring prolonged, multisite procedures. Custom implants may eliminate the need for bone harvesting, but usually require staged procedures with interim bony defects. We report the use of preoperative cranial modeling and implant design, allowing for a single reconstructive procedure. A 32-year-old woman with McCune-Albright syndrome was referred to Neurosurgery and Ophthalmology for right facial pain, deformity, and eye pressure. Examination revealed a 6-mm right eye proptosis and decreased sensation and severe pain in the right V2 distribution. Imaging demonstrated extensive fibrous dysplasia, with right orbital mass effect and nerve compression. A single procedure was planned to remove and replace the involved bone. High-resolution CT was used to create a scale model of the patient's cranium. The planned resection was performed on the model, allowing for preoperative custom implant design. We then performed single-stage resection and reconstruction. The right superior and lateral orbital rims, portions of the left superior and medial orbital rims, and the nasion were resected. The custom implant was contoured to fit and remaining small defects were filled with Fast Set Norian. No complications occurred. At follow-up, the patient reported pain and pressure relief, and examination showed resolution of proptosis, improved sensation, and excellent cosmesis. Preoperative cranial modeling and implant design allows for a shorter, one-step resection and reconstruction procedure without compromising structural or cosmetic outcome.

Reconstruction following Middle Fossa Resections

Reconstruction of the skull base following resection of tumors invading the middle cranial fossa must include the following considerations: elimination of intracranial dead space, provision of a watertight seal between the intracranial compartment and the upper aerodigestive tract, and the rebuilding of resected calvarium, scalp, facial skeleton, and the facial cutaneous covering. Dead space in the middle fossa thus is commonly effaced with fat grafts. Dural resection is often required in the resection of malignant disease. Fascia lata, temporalis fascia, lyophilized dura, and bovine pericardium are the most usual substitutes. In scalp malignancy that invades the middle fossa, calvarium as well as excised scalp require replacement. When the bone is replaced, titanium mesh is used. Large resections of scalp are often replaced with free flaps, especially the latissimus dorsi flap. The calvarial portion is covered with the overlying skin and the remaining defect with a split thickness skin graft is applied to the remaining exposed latissimus muscle. Facial malignancy resections require resurfacing as well as restoration of ostectomy defects. Bony fixation with mini- and microplates restore the skeletal elements temporarily removed for surgical exposure; those removed because of tumor invasion can be restored with split calvarial grafts.

Immediate loading of dental implants placed in severely resorbed edentulous mandibles reconstructed with autogenous calvarial grafts

The aim of this prospective study was to present the clinical outcome of immediately loaded dental implants placed in edentulous, severely atrophied mandibles, after reconstruction with autogenous multilayered calvarial grafts. Six patients, two males and four females, aged 40-67 years (mean: 56 years) presenting with severely atrophied edentulous mandibles (Cawood and Howell class VI), were reconstructed with multilayered calvarial bone grafts placed in the intraforaminal area of the mandible. Five to 8 months afterwards, 23 dental implants were placed in the reconstructed areas (three to four implants per patient) and immediately loaded with implant-supported overdentures. Patients were followed with clinical and radiographic controls annually. Recovery after the reconstruction was uneventful in all patients. All 23 implants were osseointegrated 1-3 years after the start of immediate loading. The survival and success rates of implants were 100% and 95.7%, respectively. Results from this study showed that immediate loading of dental implants placed in severely atrophied edentulous mandibles reconstructed with calvarial bone grafts is a predictable procedure, which permits a successful dental rehabilitation with a shortening of treatment times.

Individually preformed titanium mesh implants for a true-to-original repair of orbital fractures

The purpose of this investigation is to present the results using preoperatively-formed titanium mesh implants for a true-to-original primary repair of extensive orbital floor and medial wall fractures. Individually preformed implants were used to repair extensive orbital floor injuries in 19 patients at the University Hospital, Freiburg. The form of the orbital floor and walls was analysed by preoperative diagnostic CT scan data. The form of the virtual reconstructed orbit was transformed into a model of the orbital cavity by a template machine. Postoperative imaging by or CT scan verified the exact 3D reconstruction of the orbital cavity ‘true to original’. None of the patients demonstrated diplopia or enophthalmos postoperatively. Using individually preformed titanium mesh implants, the accuracy of the 3D orbital reconstruction was within a range of 1 mm. The reconstruction using preformed implants proved to be less time consuming, more precise and less invasive, compared to ‘free hand’ efforts, for the repair of orbital injuries using titanium mesh and calvarial grafts.

Age-related changes of cell outgrowth from rat calvarial and mandibular bone in vitro

To establish whether within an autograft ageing has an impact on the number of cells capable of responding to growth and differentiation factors released at defect sites. The number of cells that grow out from calvarial and mandibular explants of rats 6 weeks and 9 months of age was evaluated and their response to mitogenic, chemotactic, and differentiation factors was characterized in vitro. The cell number was determined by automated counting, proliferation was evaluated by measuring the amount of (tritiated) (3)[H]thymidine incorporated into the DNA, and migration was assessed with the modified Boyden chamber assay. Alkaline phosphatase activity served as a marker of osteogenic differentiation. A confluent layer of cells was observed in mandibular and calvarial explant cultures derived from young rats within 10 days, while only sporadic cells were counted in cultures from adult animals. The number of cells derived from calvarial and mandibular bone of young rats was nine and five times higher, respectively, than that in explants from adult rats. Cells isolated from calvarial and mandibular explants responded to platelet-released supernatant by increased proliferation and migration in both age groups. Upon incubation with bone morphogenetic protein (BMP-6), the alkaline phosphatase activity of calvaria-derived cells from both age groups was higher than in unstimulated controls. Only one sample of cells derived from mandibular explants showed responsiveness to BMP-6 in the young age group, whereas none of the cell samples responded to BMP-6 in the adult age group. The number of cells capable of growing out from mandibular and calvarial grafts in vitro is lower in adult animals than in young animals. However, bone-derived cells from both young and adult rats respond to growth and differentiation factors present at defect sites, while there are topographic differences in the responsiveness to BMP-6.