Ralph E. Holmes

Maxillary sinus augmentation: Histomorphometric analysis of graft materials for maxillary sinus floor augmentation

This study used histomorphometric analysis to quantitate the bone composition of four different sinus grafting materials biopsied at the time of implant installation. The study consisted of five patients in whom eight bone biopsies were obtained from seven grafted sites. The grafting materials consisted of hydroxylapatite (HA) granules mixed with cortical chin bone, HA mixed with demineralized bone powder, HA alone, and cortical chin bone alone. Histomorphometry was performed using backscattered scanning electron microscopy images and a computerized image analysis system. The biopsy cores yielded 46 sections from which a total of 255 fields, measuring 2.0 mm x 2.0 mm each, were imaged and analyzed. The biopsy cores contained 44.4% bone after grafting with HA granules and chin bone, 59.4% bone after grafting with chin bone alone, 20.3% bone after grafting with HA granules alone, and 4.6% bone after grafting with HA granules and demineralized bone powder. The small number of biopsies did not permit analysis of statistical significance. However, this study demonstrated the feasibility of correlating mineralized tissue composition of different sinus grafting materials with clinical outcome after dental implant installation.

Hydroxylapatite as a bone graft substitute in orthognathic surgery: Histologic and histometric findings

The use of porous hydroxylapatite (HA) as a substitute for bone in grafting associated with orthognathic surgical procedures was studied histologically and histometrically. The surgical procedures included maxillary downgrafting, advancement, setback, superior repositioning with expansion, and mandibular advancement and chin augmentation. Seventeen biopsies were obtained from nine patients after successful healing from 4.7 to 16.4 months postoperatively. Anatomic sites of the biopsies included maxillary wall, interdental region, palatal midline, chin, and mandible. In addition, nine implants representing six planned and three unplanned exposures were retrieved from nine patients. One biopsy from a successful implant was decalcified and thin-sectioned to provide better cell detail of the antral lining of the implant. The remaining biopsies were sectioned undecalcified to permit backscattered electron imaging with a scanning electron microscope. Each of the 17 biopsy specimens contained bone ingrowth. The decalcified specimen showed an intact submucosa with loss of the mucosal epithelium due to prolonged acid exposure. The biopsies were composed of 48.5% HA matrix, 18.0% bone ingrowth, and 33.5% soft tissue or vascular space. The HA matrix surface area averaged 9.4 mm2/mm3 with 62.1% of the surface covered by appositional bone ingrowth. The nine exposed implants contained connective tissue ingrowth only at their margins, with little or no bone being present. This graft-like biologic response to a porous HA matrix confirmed its ability to serve as a bone graft substitute in clinical applications. The absence of any decrease over time confirmed the relative permanence of the HA matrix. The lack of inflammatory cells in the biopsies, along with the formation of a connective tissue protective barrier in the exposed specimens, suggests that host responses to contamination were not impaired by the porous HA matrix.

Porous Hydroxyapatite as a Bone Graft Substitute in Cranial Reconstruction: A Histometric Study

To assess the potential of a porous hydroxyapatite matrix to serve as a bone graft substitute, bilateral 15 ± 20 mm craniectomy defects were reconstructed in 17 dogs with blocks of implant and split-rib autografts. Specimens were retrieved at 3, 6, 12, 24, and 48 months, and undecalcified sections were prepared for microscopy and histometry. The implant and graft cross-sectional areas did not change with time, documenting their equivalent ability to maintain cranial contour. Bone ingrowth extended across the implant from one cranial shelf to the other in 15 specimens. Little apparent bone ingrowth was seen in most graft specimens. Two implants and three grafts were nonunited, possibly due to lack of fixation or the orientation of the histology sections. The implant specimens were composed of 39.3 percent hydroxyapatite matrix, 17.2 percent bone ingrowth, and 43.5 percent soft-tissue ingrowth. The graft specimens were composed of 43.7 percent bone and 56.3 percent soft tissue. This study supported the thesis that a porous hydroxyapatite matrix may-function in part as a bene graft substitute. The brittle hydroxyapatite matrix undoubtedly became stronger with bone ingrowth, but the degree of cranial protection achieved was not measured in this study. The size of the cranial defect used in this study did not permit estimation of the distance over which bone ingrowth may be reliably expected. There remains a need for greater understanding of the causes of nonunion, the extent of predictable ingrowth depth, and the strength of the resultant implant-bone composite.

Artecoll: A Long-lasting Injectable Wrinkle Filler Material: Report of a Controlled, Randomized, Multicenter Clinical Trial of 251 Subjects

Artecoll, an injectable wrinkle filler composed of polymethylmethacrylate microspheres and bovine collagen, is widely available outside the United States. For domestic availability, a multicenter Investigational Device Exemption study was required by the U.S. Food and Drug Administration. This study consisted of 251 subjects at eight centers who received injections of Artecoll or the currently approved collagen dermal filler (control) in 1334 wrinkles of the glabella, nasolabial fold, radial upper lip lines, and corner-of-the-mouth lines. The treatments were randomized, and follow-up safety, efficacy, investigator success rating, and subject satisfaction rating data were collected at 1, 3, and 6 months. The safety data, measured as adverse events and immunoglobulin G serum levels, were low and similar for both groups. The efficacy data, measured by masked observers using a photographic facial fold assessment scale, demonstrated a combined significant improvement with Artecoll compared with collagen at 6 months (p < 0.001). At 6 months, the investigator success ratings and the subject satisfaction ratings for each of the four injections sites were superior for Artecoll (p < 0.001). In the Artecoll group, 12-month follow-up was obtained for 111 subjects (86.7 percent) and showed persistence of significant augmentation. Artecoll had fewer adverse events reported throughout the 12-month safety study period than the control group did in 6 months, although the difference was not statistically significant.

Porous hydroxylapatite as a bone graft substitute in mandibular contour augmentation: A histometric study

The buccal contour of the mandible was augmented in 17 dogs with 5 X 7.5 X 20 mm blocks of porous hydroxylapatite (HA) on one side and two-layered split rib autografts on the other. Both specimens were retrieved at three, six, 12, 24, and 48 months. Undecalcified sections were prepared for microradiography, light and UV microscopy, and histometry. A transmitted light video image digitizing system was used to trace implant and graft perimeters and calculate cross sectional areas. This system was also used to measure graft density and calculate bone and soft tissue compositions. The HA matrix, bone and soft tissue compositions of implant specimens were measured with a backscattered scanning electron microscope imaging digitizing system. All grafts became increasingly resorbed with time whereas all implants remained intact. Mature osteotonic bone ingrowth was present in all implants except one which failed to unite with the mandibular cortex. The mean graft areas decreased from 30.8 mm2 at three months to 0.7 mm2 at 48 months, while the implant areas averaged 35.5 mm2 and remained stable. The graft specimens were composed of 46.6% bone and 53.4% soft tissue or fluid space. The implant specimens were composed of 34.5% HA matrix, 28.6% bone, and 33.9% soft tissue. The HA matrix had a surface area of 9.8 mm2/mm3 that was 61.9% covered with bone ingrowth and 38.1% covered with soft tissue or fluid space. In contrast to the rapid resorption of graft onlays, the porous HA matrix demonstrated a long-term permanence with maintenance of contour and osseous incorporation over the four-year duration of this study.

ArteFill : A long-lasting injectable wrinkle filler material-summary of the U.S. Food and Drug Administration trials and a progress report on 4- to 5-year outcomes

Summary: ArteFill, the successor product to Artecoll, is an injectable wrinkle filler composed of polymethylmethacrylate microspheres and bovine collagen, which offers long-lasting and probably permanent augmentation of wrinkles and skin contour deformities. The pivotal U.S. Food and Drug Administration study consisted of 251 subjects at eight centers in the United States who received injections of ArteFill or bovine collagen dermal filler (control) in 1334 wrinkles of the glabella, nasolabial folds, radial upper lip lines, and corners of the mouth. The efficacy data generated by masked observers using a photographic Facial Fold Assessment Scale demonstrated a significant improvement with ArteFill compared with collagen at 6 months (p < 0.001) in the nasolabial folds. In the ArteFill group, 12-month follow-up was obtained for 111 subjects (86.7 percent) and showed persistence of significant wrinkle correction. A subgroup of 69 patients who received ArteFill were recalled 4 to 5 years later. Five patients reported six late adverse events that occurred from 2 to 5 years after the initial injection; four of the adverse events were mild cases of lumpiness and two were severe. The total number of late adverse events was six of 272 (2.2 percent) wrinkles injected. Among the 272 wrinkles evaluated at 5 years, two events (0.7 percent) in one patient were rated as severe (a nodular, minimally inflammatory to noninflammatory reaction in both nasolabial folds). Investigator Facial Fold Assessment ratings at 4 to 5 years were improved from baseline by 1.67 points (p < 0.001).

BONE RESPONSE TO IMPLANT SURFACE MORPHOLOGY

This study was designed to measure implant osseointegration using different surface treatments. Bilateral distal intramedullary implantation of titanium cylinders 25 mm x 5 mm was performed in 60 rabbits. The 3 surfaces tested were fiber mesh, mean pore size 400 microns; grit-blasted, mean surface roughness 6 microns; and acid-etched, mean surface roughness 18 microns. Scanning electron microscopy was used to measure the percentage of the surface of each implant in contact with bone at 2, 6, and 12 weeks postimplantation. Mechanical pull-out testing of the bone-implant interface was performed at 12 weeks. Overall, acid-etched surfaces demonstrated greater mean osseointegration than fiber mesh surfaces. All 3 surfaces demonstrated similar interface strengths. Acid etching has potential as a means of enhancing bony apposition in cementless fixation.

Bone formation and implant degradation of coralline porous ceramics placed in bone and ectopic sites

PURPOSE This study was undertaken to determine the resorption rate of porous ceramic implants. The hypothesis was that implants placed in soft tissues would degrade more rapidly than implants placed in bone. MATERIALS AND METHODS To test this hypothesis, implants were manufactured by applying a thin coating of hydroxylapatite onto an interconnected, porous calcium carbonate substrate. Control implants were made entirely of hydroxylapatite with identical microstructure. Two adult dogs received a total of 56 implants placed in the femur, skeletal muscle, and subcutaneous tissues. After killing the animals at 4 months, the specimens were removed, embedded in plastic, sectioned, and either stained for light microscopic examination or subjected to quantitative image analysis using a scanning electron microscope. RESULTS Contrary to the hypothesis, the rate of degradation was faster for implants placed in bone than in soft tissue. Within the 4 months, degradation was 24% to 63% in bone, depending on the composition. However, it was not statistically significant in either intramuscular or subcutaneous tissue. A surprising observation was that bone ingrowth occurred in 67% of the implants placed in soft tissues. On average, it was 4.3% in intramuscular sites and 6.6% in subcutaneous sites. This bone was histologically normal in 71% of the implants containing bone. CONCLUSION This study demonstrates that porous ceramic implants composed of hydroxylapatite on calcium carbonate will degrade more rapidly in bone defects than in soft tissue sites. In addition, implants with interconnected porosity and surfaces of hydroxylapatite will become ingrown with bone even after placement in soft tissues. The exact mechanisms for both of these phenomena are not understood.

Identifying potential regulators of infantile hemangioma progression through large-scale expression analysis: a possible role for the immune system and indoleamine 2,3 dioxygenase (IDO) during involution.

Hemangiomas are benign endothelial tumors. Often referred to as hemangiomas of infancy (HOI), these tumors are the most common tumor of infancy. Most of these lesions proliferate rapidly in the first months of life, and subsequently slowly involute during early childhood without significant complications. However, they often develop on the head or neck, and may pose a significant cosmetic concern for families. In addition, a fraction of these tumors can grow explosively and ulcerate, bleed, or obstruct vision or airway structures. Current treatments for these tumors are associated with significant side effects, and our knowledge of the biology of hemangiomas is limited. The natural evolution of these lesions creates a unique opportunity to study the changes in gene expression that occur as the endothelium of these tumors proliferates and then subsequently regresses. Such information may also increase our understanding of the basic principals of angiogenesis in normal and abnormal tissue. We have performed large-scale genomic analysis of hemangioma gene expression using DNA microarrays. We recently identified insulin-like growth factor 2 as a potentially important regulator of hemangioma growth using this approach. However, little is known about the mechanisms involved in hemangioma involution. Here we explore the idea that hemangioma involution might be an immune-mediated process and present data to support this concept. We also demonstrate that proliferating hemangiomas express indoleamine 2,3 dioxygenase (IDO) and discuss a possible mechanism that accounts for the often slow regression of these lesions.

Bone-graft reconstruction of the monkey orbital floor with iliac grafts and titanium mesh plates: A histometric study

Bone-graft reconstruction of large orbital defects has been difficult because of a lack of marginal support of the grafts and unpredictable reserption. A titanium mesh orbital plate has been developed to provide this marginal support for bone grafts. However, the problem of unpredictable bone-graft resorption remains. To determine if this plate has any effect on graft resorption, this study was designed to quantitate the dimensions and composition of bone autografts (1) with and without titanium plate support and (2) in the anterior and posterior orbit. Bilateral full-thickness large orbital floor defects were surgically created in five monkeys, and a titanium orbital floor plate was fixed with screws into the right orbit. Two iliac crest grafts were measured and placed transversely and without fixation in each orbit, one anterior and the other posterior to the axis of the globe. The orbits were retrieved 28 weeks after surgery and were analyzed histologically and histometrically. Comparison of the supported and nonsupported grafts revealed no differences in their histologic appearance. There were three significant histometric findings: (1) resorption of bone was similar for those grafts which spanned an orbital floor defect and those which were supported by a titanium plate; (2) resorption of grafts in the posterior orbit did not differ from that of grafts in the anterior orbit; and (3) resorption of approximately one-third of bone-graft thickness and width had taken place during the 28-week study interval. We conclude that the benefits of bone-graft support by a titanium mesh orbital floor plate are not offset by any alteration in bone-graft resorption.