56. Bone - Osseous Surgery - V Augmentation

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Rapid Search Terms

1. review of bone substitutes
2. bioceramics
   1. durapatite (Periograft)
   2. tricalcium phosphate (Synthograft)
3. bioactive glass (Perioglass)
4. other alloplasts
   1. Bioplant HTR
5. possible complications in using alloplasts
6. xenografts
   1. bovine-derived xenograft (PepGen)
   2. porous bone mineral  (BioOss)

Discussion Topics

What is a bone substitute? Are all bone substitutes alloplasts? What are the different types of alloplasts and how have they been studied? How do these grafted sites heal? How would this affect treatment options for the patient in the future if the tooth would ever need to be extracted?

1. Aichelmann-Reidy ME, Yukna RA. Bone replacement grafts. The bone substitutes. Dent Clin NA 42:491-503, 1998.

2. Nasr, H., Aichelman – Reidy, M, Yukna, R.: Bone and bone substitutes. Periodontol 2000 19:74-86, 1999.

What is a bioceramic? What is the theory behind using these materials? Is calcium phosphate found in the human body? Are all of these materials made the same, and if not, how are they different? What is the outcome of implanting a calcium phosphate material? What other than calcium phosphate has been studied and what is it’s origin?

3. Froum SJ, et al: Human clinical and histologic responses to Durapatite implants in intraosseous lesions. Case Reports. J. Periodontol. 53:719-725, 1982.

4. Froum S, Stahl S: Human intraosseous healing responses to the placement of tricalcium phosphate ceramic implants. II. Thirteen to eighteen months. J Periodontol 58:103-109, 1987

5. Nagahara, K et al: Osteogenesis of Hydroxyapaptite and Tricalcium Phorphate Used as a Bone Substitute. J Oral Max Impl 7, 72-79, 1992

6. Barnett JD, Mellonig JT, Gray JL, Towle HJ: Comparison of freeze-driedbone allograft and porous hydroxylapatite in human periodontal defects. J. Periodontol. 60:231-237, 1989.

What is bioactive glass? How does this heal when placed in a defect? What would be the indications and contraindications for a material such as this?

7. Nevins ML, Camelo M, Nevins M, et al. Human histologic evaluation of bioactive ceramic in the treatment of periodontal osseous defects. Int J Perio Rest Dent 20:459-467, 2000.

Have other alloplasts been studied for use in periodontal treatment? How do they perform clinically and histologically?

8. Plotzke AE, Barbosa S, Nasjleta CE, Morrison EC, Caffesse RG. Histologic and histometric responses to polymeric composite grafts. J Periodontol 1993; 64:343-348.

What are some of the negative consequences of using these materials? Why would you NOT want to use a particular material? When you are practicing, how will you support using or not using a particular material?

9. Ibbott CG. Root resorption associated with placement of a ceramic implant. J. Periodontol. 56:419-421, 1985.

10. Brown GD, Mealey BL, et al. Hydroxyapatite cement implant for regeneration of periodontal osseous defects in humans. J Periodontol 69:146-157, 1998.

What is a xenograft? How do these materials compare when used in treating periodontal osseous defects? What are some biologic and clinical concerns related to the use of xenografts ? How have they evolved over time? Is bovine-derived the only known type of xenograft?

11. Beube FE: A study on reattachment of the supporting structures of the teeth. J. Periodontol. 18: 55-56, 1947.

12. Nielson IM, Ellegaard B, Karring T: Kielbone in new attachment attempts in humans. J. Periodontol. 52:723-728, 1981

13. Richardson CR, Mellonig JT, et al. Clinical evaluation of Bio-Oss: a bovine-derived xenograft for the treatment of periodontal osseous defects in humans. J Clin Perio 26:421-428, 1999.

14. Sogal A, Tofe AJ. Risk assessment of bovine spongiform encephalopathy transmission through bone graft material derived from bovine bone used for dental applications. J Periodontol 70:1053-1063, 1999.

15. Yukna, R.A., Yukna, C.N: A 5 – year follow-up of 16 patients treated with coralline calcium carbonate (Biocoral™) bone replacement grafts in infrabony defects. J Clin Periodontol 25:1036-1040, 1998

What modifications have been made to bovine-derived xenograft? Does this improve its outcome? How does adding a. antibiotics, b. membrane or c. collagen effect the clinical outcome?

16. Yukna RA, Krauser JT, Callan DP, Evans GH, et al. Multicenter clinical comparison of combination anorganic bovine-derived hydroxylapatite matrix (ABM)/cell binding peptide (P-15) and ABM in human periodontal osseous defects. 6 month results. J Periodontol 2000; 71:1671-1679.

17. Yukna RA, et al. Thirty-six month follow-up of 25 patients treated with combination anorganic bovine-derived hydroxyapatite matrix (ABM)/Cell-binding peptide (P-15) bone replacement grafts in human infrabony defects. I. Clinical findings. J Periodontol 2002;73:123-128.

18. Camelo M, Nevins ML, et al. Clinical, radiographic, and histologic evaluation ofhuman periodontal defects treated with Bio-Oss and Bio-Gide. Int J Periodont Rest Dent 1998; 18: 321-331.

19. Mellonig JT. Human histologic evaluation of a bovine-derived bone xenograft in the treatment of periodontal osseous defects. Int J Perio Rest Dent 20:19-29, 2000.

20. Stavropoulos A, Karring ES, Kostopouos L, et al: Deproteinied bovine bone and gentamicin as an adjunct to GTR in the treatment of intrabony defects: a randomized controlled clinical study. J Clin Periodontol 2003; 30: 486-495

21. Cosyn J et al. Regenerative periodontal therapy of infrabony defects using minimally invasive surgery and a collagen-enriched bovine-derived xenograft: a 1-year prospective study on clinical and aesthetic outcome. J Clin Periodontol 2012; 10: 979-986.

What is a bone substitute? Are all bone substitutes alloplasts? What are the different types of alloplasts and how have they been studied? How do these grafted sites heal? How would this affect treatment options for the patient in the future if the tooth would ever need to be extracted?

Aichelmann-Reidy Yukna 1998                    ARTICLE

Review on bone substitutes. Most bone substitutes are osteoconductive materials providing a scaffold to allow ingrowth and deposition of bone. Bone substitutes can lad to significant improvements in clinical probing depth and attachment levels but limited periodontal regeneration.

Xenografts

• Bovine-derived hydroxiapatite

• Coralline calcium carbonate

Alloplasts

• Bioceramics

• Tricalcium phosphate

• Hydroxyapatite

• Dense, nonporous, nonresorbable

• Porous, nonresorbable (xenograft)

• Resorbable, low-temp derived

• Bioactive glasses

• Polymers

Xenografts: osteoconductive, readily available

Bovine bone: is processed to obtain natural bone without organic component (similar to human bone to improve osteoconductive capabilities). Anorganic bone is the hydroxyapatite (HA) skeleton (highly porous and similar to cancellous bone) that remains after low heat or chemical extraction of organic component.

Bovine-derived HA is deproteinated, porous (supports cell-mediated resorption). Has been used successfully for infrabony defects and ridge augmentation. Two products currently use: Osteograft/N and BioOss.

Coralline calcium carbonate: Biocoral is obtained from natural coral. Composed of aragonite. Biocompatible and resorbable. Pore size 100-200 um. No encapsulation has been reported. Significant gain in clinical attachment, reduction in probing depth and defect fill.

Alloplasts:

Bioceramics: Composed of calcium phosphate. Two widely used forms: Tricalcium phosphate and HA. TCP(B-tricalcium phosphate) has similar Calcium phosphate proportions to bone. Biologic filler that serves first as scaffold, then permits replacement with new bone. Results are not always predictable, does not seem to initiate osteogenesis. The particles become encapsulated by connective tissue and do not stimulate bone growth.

HA: Resorbability is determined by the temperature at which it forms.

a. When prepared at high temperature (sintered), it is nonresorbable, nonporous, dense and larger crystal size. Osteophyllic, osteoconductive and acts as inert filler.

b. Porous HA (Interpore 200) is obtained by hydrothermal conversion of the natural coral into HA. 190-200 um particles which allow fibrovascular ingrowth & subsequent bone formation

c. Resorbable, low-temp HA: OsteoGen and OsteoGraft LD are nonsintered (nonceramic) with particles between 300-400 um. Proposed to act as mineral reservoir and as scaffold inducing new bone formation due to its slow resorption rate. Has been used in preparation for endosseous implants and sinus augmentation. HA as a bone substitute is not osteoinductive but osteoconductive. Some osteogenic activity reported with porous HA

Bioactive glasses- when exposed to tissue fluids in vivo, the material is covered by a double layer of silica &Calcium phosphorous rich (apatite) layer that allows adsorption & concentration of proteins guiding & promoting osteogenesis. Two forms:

PerioGlas- synthetic bone graft particulate- 90-710 um, appears to be osteoconductive and also to act as biologic membrane.

Biogran- resorbable synthetic bone graft. 300-355 um particle size appears to be advantageous for guiding osteogenesis. Small cracks on calcium phosphorous layer allows penetration of phagocytic cells and resorption of the gel, which favors adherence, differentiation and proliferation of osteoprogenitor cells. In theory, Biogran has clinical advantages over PerioGlas, but no human studies are available.

Clinical and Histological comparisons: Mean defect fill of 60-70% can be anticipated with bone substitutes. Surgical debridement alone can yield to 10-30% defect fill. Autogenous or allogenic graft materials produce similar clinical defect fill as do bone substitutes for infrabony defects. At implant site preparation, bone density has greater importance; in treatment of infrabony defects new attach is the goal. Clinically acceptable results have been reported with graft materials encapsulated within connective tissue.

Nasr Aichelmann-Reidy Yukna 1998                    ARTICLE

Review on bone substitutes.

Xenografts

• Bovine-derived hydroxiapatite

• Coralline Ca carbonate

Alloplasts

• Bioceramics

• Tricalcium phosphate

• Hydroxiapatite

• Dense, nonporous, nonresorbable

• Porous, nonresorbable (xenograft)

• Resorbable, low-temp derived

• Bioactive glasses

• Polymers

Xenografts: osteoconductive, readily available. Bovine bone is processed to obtain natural bone w/o organic component ( to human bone to improve osteoconductive capabilities). Anorganic bone is the HA skeleton (highly porous & to cancellous bone) that remains a/f heat or chemical removal of organic componenet. Deproteinated , porous (supports cell-mediated resorption)..Have been used successfully for infrabny defects or ridge augmentation,eg: Osteograft/N &BioOss.Coralline Calcium carbonate: Biocoral is obtained from natural coral. Composed of aragonite. Biocompatible & resorbable. 100-200 um. No encapsulation has been reported. S CAL gain,  PD and defect fill.

Alloplasts: Bioceramics: Composed of calcium phosphate. Two widely used forms: Tricalcium phosphate & HA. *TCP(B-tricalcium phosphate) has similar Ca-P proportions to bone. Biologic filler that serves 1^st as scaffold, then permits replacement w/new bone. Results not always predictable, does initiate osteogenesis, particle encapsulated by CT.

*HA: Resorbability is determined by the temp. at which it forms. 1)When prepared at high temp (sintered), HA is nonresorbable, nonporous & dense and larger crystal size..Osteophyllic, osteoconductive & acts as inert filler. 2) Porous HA (Interpore 200) is obtained by hydrothermal conversion of the natural coral into HA. 190-200 um part allow fibrovascular ingrowth & subsequent boen formation 3) Resorbable, low-temp HA: OsteoGen&OsteoGraft LD are nonsintered (nonceramic) w/ particle b/w300-400 um. Proposed to act as mineral reservoir and as scaffold inducing new bone formation due to its slow resorption rate. Has been used in DI preps and sinus augmentation. HA is osteoconductive; some osteogenic activity reported w/porous HA Bioactive glasses-. when exposed to tisue fluids in vivo, the material is covered by a double layer of silica &Ca-P(apatite)-rich layer that allows adsorption & concentration of proteins guiding & promoting osteogenesis. Two forms: PerioGlass- synthetic bone graft particulate- 90-710 um, appears to be osteoconductive and also to act as biologic membrane. Biogran- resorbable synthetic bone graft. 300-355 um particle size appears to be advantageous for guiding osteogenesis. differentiation and proliferation of osteoprogenitor cells. In theory, Biogran has clin advantages over PerioGlass, but no human studies are available.

Clinical & Histologic comparisons: 60-70% mean defect fill can be anticipated w/bone substitutes. OFD alone can yield to 10-30% defect fill. Auto or allografts produce similar clinical defect fill as do bone substitutes for infrabny defects. At implant site prep, bone density has greater importance; in tx of infrabny defects new attachment is the goal. Clinical acceptable results have been reported w/ graft material encapsulated into CT.

What is a bioceramic? What is the theory behind using these materials? Is calcium phosphate found in the human body? Are all of these materials made the same, and if not, how are they different? What is the outcome of implanting a calcium phosphate material? What other than calcium phosphate has been studied and what is it’s origin?

Froum 1982                    ARTICLE

P: to evaluate clinically and histologically the healing after implantation of nonresorbable ceramic (Durapatite – Periograft) into human periodontal osseous defects.

M & M: 4 tooth-containing blocks were obtained from 4 patients who had received Durapatite implants in osseous defects (combination, 1-wall and 3-wall circumferential, and 3-wall wide). Each defect exceeded 4 mm in depth measured with stent. Each patient was seen for 5 to 13 post-surgical maintenance visits. Teeth in block sections were removed between 8 weeks and 8 months post-surgery.

R: Clinical evaluation of the repair process demonstrated that probing depths were decreased in all 4 cases (mean pre-op PD 11.1 mm, mean post-op PD 6.5 mm). Histological evaluation of the repair process showed no indication of new periodontal attachment, osteogenesis or cementogenesis in the host tissues adjacent to the graft particles. Pocket closure appeared to occur by means of a long junctional epithelium and connective tissue adhesions. There was minimal or no evidence of inflammation in all sections associated with the implant. The graft material was encapsulated by collagen, therefore this acted as a biocompatible foreign body within the gingival tissue.

BL: Durapatite served adequately as a foreign body “filler” and was well tolerated. No new attachment was found

Froum 1987                    ARTICLE

P: To evaluate healing responses to Tricalcium Phosphate Ceramic Implants over a 13-18 months. SYNTHOGRAFT

M&M: 5 periodontal lesions (1-2 wall defect) in a healthy 40-year-old female volunteer patient were selected. These sites were diagnosed as having hopeless prognosis. Placed notch at gingival margin. FTF was reflected, prior to debridement roots received a notch in the most apical extension of calculus. The lesion was thoroughly debrided and measurements were taken. Following intramarrow penetration, the site was overfilled with the ceramic graft material. Flap was coronally positioned and complete closure was attempted. Pt received weekly plaque removal for the first 6 weeks and then once every 2-4 weeks until block sections were removed (13-18 months after graft placement). At time of block removal, radiographs were taken, PD, REC, clinical attachment gain were evaluated. Pre-op PD ranged from 8.5 to 13.2 mm & alveolar crest margin to depth of defect ranged from 3.2 mm to 8.7 mm.

R: Post-op PD decreased and ranged from 4.3 mm to 7.2 mm. Gingival recession was present at all sites and ranged from 1.9 mm to 3.0 mm (apical to marginal notch). Clinical attachment gain ranged from 1.7mm to 3mm. Histologic analysis: limited presence of graft particles at operative sites. The graft particles were surrounded by dense connective tissue. They did not induce inflammation, nor did they appear to enhance osteogenesis or cementogenesis. Healing by a LJE was observed. Limited evidence of new connective tissue. Root resorption was seen at the most apical position of the JE, cementogenesis had taken place at these sites and functionally attached fibers inserted into this cellular cementum.

CON: Data did not indicate significant new attachment, cementogenesis or osteogenesis in healing of periodontal lesions in the presence of TCP grafts in 13-18 months after placement.

Nagahara 1992                    NO ARTICLE

B: Two kinds of inorganic calcium phosphate: biodegradable (tricalcium phosphate (TCP) and hydroxyapatite (HA) sintered at low temps) and nonbiodegradable (HA sintered at high temps)

P: To examine the transmission electron microscopic (TEM ) and histochemical transmission electron microscopic findings between HA and TCP and adjacent tissue, and enzymatic activities associated with osteogenesis and these implanted materials up to 4 weeks postoperatively.

M+M: Male Wister rats were used in this study. The HA and TCP granules were inserted into the bone marrow space of the rat femur. The animals were sacrificed at 1, 2, 3, and 4 weeks after implantation and prepared for histo. Transmission electron microscopy was used for analysis. Alkaline phosphatase activity was also measured.

R: The microscopic results indicated that TCP resorbed more rapidly than HA after implantation, with a notable breakdown of material and replacement by mesenchymal cells with ultrastructural features resembling osteoprogenitor cells and collagen up to 4 weeks postop.

• 1 week – Mesenchymal cells were found in close association with HA. A reduction of TCP granules with evidence of resorption: small fragments of TCP were within cytoplasm of mesenchymal cells.

• 2 weeks – Implanted HA granules showed early stages of calcification with closely approximated osteoblasts. A reduced number of TCP granules noted, and slender collagen like filaments were scattered throughout interfacial zone.

• 3 weeks – In the HA sample, collagen fibers were found to be parallel to the HA surface. The TCP granules remaining were covered with bone tissue with collagen fibers around tangentially to granules.

• 4 weeks – The HA sample showed reduction of number of HA granules, possibly thru resorption, and replacement of HA granules by a mineralized tissue. For TCP, an irregular appearance was seen with an increase in cellular components interspersed with osseous like tissue. Some areas completely devoid of TCP, some showed intracellular TCP material indicating continued resorption.

At 1 week, Alkaline phosphatase activity was seen in all samples of the HA, but not in the TCP treated areas. At 2 weeks, both tissues had alkaline phosphatase activity in mesenchymal cells that resembled osteoblasts. At 4 weeks, alkaline phosphatase activity only seen in bone tissue associated with HA granules. Acid phosphatase activity was noted only with the TCP granules

BL: HA and TCP implanted materials both stimulate bone metabolism. The histo demonstrated more osteogenesis events around the HA particles, both earlier and faster than around TCP. TCP undergoes resorption more readily. The alkaline phosphatase activity seen in segments with HA indicate that HA stimulates osteogenesis changes in the tissue surrounding whereas acid phosphatase present with TCP granules is generally seen with osteoclasts.

Barnett 1989                    ARTICLE

P: To clinically compare FDBA and porous HA granules in human periodontal infraosseous defects.

M&M: Seven pt with at least 2 pairs of infraosseous perio defects had initial therapy performed (including occlusal adjustment if necessary). FTF elevated, defects debrided and roots planed. The number of bony walls and measurements from the CEJ to the bony crest and to the bottom of the defect were recorded. Every pt had at least one defect treated with each graft material. Flaps were sutured and dressing was placed. Pt recalled once a month for OH and between 6 and 11 months, re-entry was performed to evaluate the tissue response and correct any residual defects. The soft tissue that was curetted from re-entered sites was sent for histology. Standard PA x-rays, PPD, vitality, mobility, and BOP were recorded before Sx and at re-entry.

R: There were 19 pairs of defects evaluated in 7 pt. No significant difference was found between FDBA and porous HA in the initial osseous defects. There was no significan difference in osseous repair between FDBA (2.1mm) vs HA (1.3mm). FDBA had slightly more gain of clinical attachment (2.2mm vs 1.3mm) and greater probing depth reduction (3.0mm vs 1.4mm) than HA. With FDBA, 74% of the sites showed more than 50% bone fill, while this was the case only in 42% of the HA group (however, not statistically significant). Histological analysis of curetted tissue at re-entry showed minimal osteogenic activity with either group. HA appeared encapsulated in more instances than FDBA.

BL: FDBA may have some enhanced reparative potential when compared to granular porous hydroxylapatite in the tx of human periodontal defects.

Cr: No stent used to take measurement with probe.

What is bioactive glass? How does this heal when placed in a defect? What would be the indications and contraindications for a material such as this?

Nevins 2000                    ARTICLE
Purpose: To determine the type of healing that occurs in human intrabony defects following placement of a bioactive ceramic (PerioGlas) histologically, determine the biocompatibility, the osteoconductive potential of the material and evaluate the clinical and radiographic results of the regenerative procedures.

Materials and methods: 5 patients with severe periodontal disease and a hopeless dentition. One tooth per patient was selected for the study. SRP was performed on all 4 quadrants and surgery was performed within 4 weeks.

Stents were fabricated for standardized clinical and surgical measurements including AL, recession, PD.

During the surgery full thickness flaps were elevated one tooth mesial and distal to the intrabony defect. Defects were degranulated, base of the defects were marked on the teeth, SRP was performed and PerioGlas was placed according to manufacturer’s direction and flaps were sutured coronally.

Follow-up visits to monitor safety and healing were performed on days 2, 4, 7, 14, 28 and then at 2,3,4,5 and 6 months.

Clinical measurements were repeated at 6 months and block biopsies were obtained at 7 months (cases 1,2,3) and 12 months (cases 4,5).

After block extractions blocks were grafted with a bone graft and use of barrier membranes to reconstruct the site.

Results:

Case 1: 3mm 2-wall defect. After 7 months the attachment level increased by 2mm and there was 1mm of recession. The 6 month post-op radiograph indicated evidence of bone fill. Histologically PerioGlas was surrounded by connective tissue. No regeneration.

Case 2: 4mm intrabony defect extending to mesial and palatal surfaces. Post-op radiographs showed clear delineation between the host bone and the grafted material. No evidence of periodontal regeneration.

Case 3: Deep and wide intrabony defect on the mesial of mand. 2^nd molar. LJE extending to the base of the defect, minimal new connective tissue attachment, no new bone formation or cementum. No regeneration.

Case 4: One- and two- wall defect on the mesial and mesiobuccal surfaces of max 1^st premolar. Minimal new bone formation to the borders of the defect, root surface was lined by long junctional epithelium, minimal new CT, no new cementum. No regeneration.

Case 5: Circumferential intrabony defect on the palatal and mesial of max 2^nd premolar. Post –op radiograph showed resolution of the defect. Histologically it healed with LJE, no new connective tissue attachment and limited bone formation around the apical particles of the grafting material. No regeneration.

In this case an extraction socket was also grafted and showed no evidence of new bone formation.

Conclusion: 1) Histologic analysis showed healing by LJE with minimal connective tissue attachment, graft particles were embedded in dense connective tissue with minimal inflammatory infiltrate and minimal new bone formation in the apical border.

2) Mean 2.7mm of clinical PD reduction, 2.2mm of clinical attachment gain and 0.5 mm recession (the authors do not mention the baseline measurements for all the defects).

3) Radiographic evaluation is not conclusive for regenerative procedures using radiopaque grafting materials. Human Histo on hopeless teeth

Have other alloplasts been studied for use in periodontal treatment? How do they perform clinically and histologically?

Plotzke 1993 Bioplant HTR                    ARTICLE

BG: Hard tissue replacement graft (HTR) has been used in plastic surgery as a filler. Past reports show clinical suitability in perio treatment as a filler.

P: To determine histologically if the non-resorbable HTR (calcium layered polymethyl and hydroxyethyl methacrylates) promotes new attachment in artificially induced bone defects in dogs.

M&M Four F dogs w/o perio dz. Surgery performed on 2 maxillary quadrants in each dog. Class II furcation defects created on buccal of 2^nd, 3rd., and 4th pre-molars. Alveolar bone level was marked by a notch on the root. HTR polymer was placed on experimental side, no graft on control side. Flaps replaced. Dogs scarified at 6 months and jaws sectioned following routine fixation. Histologic and histometric evaluation included: 1) total fill of furcation; 2) area filled with alveolar bone; 3) area filled with CT; 4) area occupied by new cementum; 5) area occupied by epithelium if present.

R: Tissue tolerated the graft well, with no sign of ankylosis, root resorption or abscess formation. Most commonly, the graft particles were encapsulated in CT. In some sections the particles were in direct contact with new alveolar bone, although there was no evidence of active bone formation. New cementum had grown to the root notches but not coronal. The epithelium had migrated apically to form a LJE. Control specimens healed by LJE. Some CAL gain, some gingival recession.

BL: Use of HTR resulted in no increase in CT &/or alveolar bone regeneration. The polymer acted as a biocompatible filler without evidence of new attachment.

*Murray and Yukna both showed HTR to result in clinical closure of Class II defects, with a better mean defect fill of 2.2 mm vs. 1.0 mm with Sx debridement. This was a small study, but had both histologic and histometric analysis yielding definitive results.

What are some of the negative consequences or complications of using these materials? Why would you NOT want to use a particular material? When you are practicing, how will you support using or not using a particular material?

Ibbott 1984                    ARTICLE

P: To present a case in which Periograf, a non-resorbable ceramic material that is supposed to be biocompatible results in root resorption.

Case: 38-year old woman, had initial therapy performed. Isolated pocket present in left lateral incisor of 7mm on the facial, and 9mm on the distal. Tooth was vital and mobility WNL. The 2-wall defect was grafted with Periograf since regeneration was unlikely at the site. Atb not prescribed and healing was uneventful.

-4 mo recall: good OH, PD 3mm, PA normal

-8 mo recall: same as 4 mo

-12 mo recall: PA showed root resorption. Mobility WNL and tooth vital. Pt did not agree to re-entry

-18 mo recall: root resorption coronal to gingival margin and the tissue was inflamed. PD 5mm and PA showed extensive root resorption. Mobility and vitality unchanged. Re-entry performed and encapsulated graft removed. Area was debrided (graft did not adhere) and simply sutured.

BL: This case is unusual because it is the first reported instance of root resorption following the use of a ceramic implant.

Brown 1998.                    ARTICLE

B: Hydroxyapatite cement (HAC) is non-ceramic and when mixed with water, blood or saliva will form a moldable paste that hardens to HA. Past studies on cranial defects show that it is biocompatible and resorbable, and possibly osteoconductive.

P: to examine the efficacy of using HAC for the regeneration of human vertical periodontal osseous defects

M&M: 16 pts (11 m, 5 f) with moderate to severe periodontal disease and 2 bilaterally similar vertical bony defects (initial PD >6 mm) had initial treatment with SRP.

Group 1: negative control – HAC in one defect and OFD at the contralateral defect

Group 2: positive control – HAC in one defect and DFDBA in the contralateral defect

Recalls every 2 weeks for 3 months, then monthly thereafter. Standardized radiographs at baseline and 12 months. PI, GI, BOP, PD, CAL recorded at baseline and 12 months with stent. Osseous measurements taken at time of surgery and at 12-month re-entry.

R: Within 6 months of graft placement, 69% of HAC-treated sites exfoliated all or most of the implant through the gingival sulcus.

	PD reduction	CAL gain	Bone fill	Crestal resorption	%Defect resolution
HAC	1.6	1.3	-	1.4	29.2
DFDBA	3.1	2.9	2.4	-0.2	41.9
FC	2.4	1.4	1.1	0.7	32.3

BL: There is no rationale available to support the use of HAC implant in its current formulation for the treatment of vertical intrabony periodontal defects

What is a xenograft? How do these materials compare when used in treating periodontal osseous defects? What are some biologic and clinical concerns related to the use of xenografts ? How have they evolved over time? Is bovine-derived the only known type of xenograft?

Beube 1947                    NO ARTICLE

Purpose: To test if the regeneration is possible in periodontal defects in dogs and humans.

M&M: 1) Dogs (28 teeth): Bone, PDL and dentin were removed from the roots of canines (concavity 6mm²). Soft tissue was maintained over denuded areas. Blood clot was formed over the defect and flaps closed. Clinical exam of the wound and Histological evaluation performed at 24h, 3.5d, 8d, 14d, 17d, 27d, 35d and 2yrs.

2) Humans (10 cases): “Conservative periodontal treatment” performed and subsequent placement (4,5,6,16,42 weeks) of boiled cow-bone powder in 5 out of the ten cases (failures). In these cases, teeth received splinting and occlusal adjustment. X-ray s taken at 24h up to 12 yrs post-op. *All defects extended to the apical third of the root or beyond and in a wide area laterally.

R: Dogs – clinical healing:

- 8d: wound edges fully healed, bleeding not induced by probing

- From 8d to two years: healing had taken place and mucosa was more normal in appearance

Dogs – microscopic healing:

- 8d: well organized granulation tissue with fibroblasts and new blood vessels, leucocytes still present.

- 14d: granulation tissue more mature. Some inflammatory cells still evident.

- 17d: islands of new bone. Fibroblastic tissue in close contact with denuded dentin surface

- 27d: fibroblastic tissue in direct contact with dentin, layer of new cementum or cementoid, new bone grown completely across the gap created on old bone. Fibroblastic tissue btw new cementum and new bone

- 35d: increase in density of cementum and bone.

- 2yrs: new bone as dense as old bone, PDL present (well organised), cementum covering the dentin and old cementum but not in uniform thickness.

Humans:

Clinically: all pockets were eliminated along with mobility.

Radiographically: New bone formation in all cases (1/4 up to 2/3 of exposed root length) in both horizontal and vertical bone defects..

Discussion: Changes in damaged soft and hard tissue includes an acute inflammatory reaction up to 3.5 days. A transition to fibroblastic tissue was observed on the 8^th day. New bone, cementum and PDL were evident by the 27^th day.

Radiographically, the average length of time for the radiolucent area to be fully replaced by new bone was 10 months.

BL: Regeneration is possible in dogs, and new bone formation also seems to be possible in teeth with previous history of periodontal disease in humans.

Nielson 1981                    ARTICLE

B: Kielbone is a deproteinized and deffatted bovine xenograft

P: To compare Kielbone to autogenous grafts in periodontal defects.

M&M: 55 patients with 92 intraboney defects were included in the study. Following initial therapy, sulcular incisions were made from the midline of adjacent teeth and the interproximal papilla was resected. The defects were debrided followed by intramarrow penetration and 46 of the defects were grafted with Kielbone, 46 were filled w/ autogenous grafts, taken from adjacent edentulous areas. A FGG was harvested from the palate, adjapted and sutured over the grafted sites. Sites were evaluated after 6mo for PD, CAL and bone fill.

R: The average pre-op PD was 7.6mm for Kielbone and 7.7mm for autogenous. Post op values were 2.5mm for Kielbone and 2.1mm for autogenous. Recession post op for the Kielbone sites: 1.6 and for autogenous: 2.1. 37% of the Kielbone sites and 39% of the autogenous sites had 75%-100% bone fill. Less that 50% bone fill was noted in 33% of the Kielbone treated sites and 35% of autogenous.

BL: Statistically, there was no difference in the sites grafted w/ Kielbone when compared to autogenous when evaluating attachment levels and bone fill.

Richardson Mellonig 1999                     ARTICLE

P: To compare Bio-Oss to DFDBA in the repair of human intrabony vertical defects resulting from moderate to advanced periodontal disease.

M&M: 17 healthy patients (7M/10F), with no systemic disease, 34-67 years of age, with moderate to severe adult periodontitis were included. Each pt had 2 radiographic vertical defects with PDs5mm following initial non-surgical therapy (full mouth sc/rp, OHI, occlusal adjustment as indicated). All baseline clinical parameters were obtained the day of the sx, and final parameters were obtained at re-entry sx 6 months after graft placement. Soft tissue measurements: PD, CAL, REC. Hard tissue measurements: CEJ-AC (alveolar crest), CEJ-BD (base of the defect), AC-BD. Only defects3mm were included. The defect was randomly assigned to receive either Bio-Oss or DFDBA. Intrasulcular incisions were performed, FTFs were reflected, debridement and root planing performed. Osseous defects were measured and were classified as to the numbers of walls present. The defects were grafted and filled to the existing alveolar crest. Flaps were closed and post-op instructions were given. No post-op antibiotic regimen was utilized. Pain medications and CHX 0.12% were given. Post-op appointments were performed at 7-10 days, 25-30 days, 3 months and 6 months (reentry). At 6 months soft tissue and hard tissue clinical parameters were assessed. Statistical analysis was performed.

R: 30 defects were treated in 17 patients. 14 defects were treated with DFDBA and 16 defects with Bio-Oss.

Bio-Oss group: (2) 2-walled, (2) 3-walled, (12) 2,3-walled defects

Initial clinical measurements were similar for both groups. DFDBA group: initial PD was 8.9mm, initial CAL was 7.9mm and surgical defect depth was 5.2mm. Bio-Oss group: initial PD was 8.6mm, initial CAL was 7.7mm and surgical defect depth was 5.1mm. No SSD between two groups. PD was significantly decreased in both groups but the difference was not significant between the groups. Both groups demonstrated significant improvement in CAL but there was no significant difference between the 2 materials. Both groups improved significantly with regard to bone fill, and % of defect resolution. No SSD between two groups.

CON: Significant improvement in defect parameters was seen with both DFDBA and Bio-Oss. No SSD between the two materials.

Sogal and Tofe, 1999 (Principles in company)                    ARTICLE

B: Creutzfeldt-Jacob disease (CJD) in humans has been linked to the transmission of bovine spongiform encephelopathies (BSE) from cattle to humans.

P: To report a risk analysis of possibility of transmission of BSE from commercially available bone graft substitute to humans.

M+M: A review of current literature on risk assessment of BSE transmission led to identification of two risk models: one by the German Federal Ministry of Health and another but the Pharmaceutial Research and Manufacturers Association of America (PhRMA). Both models were applied to bovine bone graft substitute (BGS), using all the appropriate equations.

R: German Federal Ministry of Health: received a total of 30 points, exceeding the 20 required for a product to be acceptable for human use. This score means that the product is 30 orders of magnitude safer than a product carrying the highest potential risk factor, and indicates that if the raw bone is acquired from a BSE free source and manufactured using high temperature, the resultant bone substitute is 10^10 times safer than product of acceptable safety.

The PhRMA BSE risk analysis: showed that 1 infection can be expected for every 1.3x10^18 of 1gram doses of BGS processed by high temperature processing from raw bone obtained from a BSE-free source.

BL: The risk of BSE transmission through bovine-derived bone substitutes manufactured from the HT process using raw bone from BSE free sources is negligible.

CR: The research is based on statistics of cattle in 1999 when there had been zero cases of BSE in U.S. cattle. There have been 3 cases of BSE identified in U.S. born cattle since this analysis was completed.

The BGS product article referring to is manufactured by CeraMed Dental known as OsteoGraf. Sogal is chief engineer, research and development of CeraMed and Tofe is President and CEO of CeraMed. Good critique

Yukna 1998                    ARTICLE

P: 5-year follow-up on coralline calcium carbonate (Biocoral) in infrabony defects

M&M: 16 of the original 22 patients were followed up, patients received phase one, 1- 2- and wide 3-wall bony defects were chosen (narrow 3-wall defects, dehiscences and furcation excluded), root surface debridement, intramarrow penetration, conditioning with tetracycline paste for 3 min followed by flushing with saline, the defects were grafted with CalCarb. Deplaquing every 10 days for 1 month, then every month for 5 months, then 3 months SPT. Re-entry was performed about 6-12 months post-surgically. Patients were then placed on regular 3-4 month recall and re-evaluated in detail at 5 years or more post-surgery (no re-entry).

R:

BL: The results obtained with grafting with Biocoral appear stable with good maintenance; the material appears comparable to other synthetic grafting materials.

What modifications have been made to bovine-derived xenograft? Does this improve its outcome? How does adding a. antibiotics, b. membrane or c. collagen effect the clinical outcome?

Yukna 2000 PepGen                    ARTICLE

Purpose: To compare the treatment response to anorganic bovine – derived HA bone matrix (ABM) with P-15 (synthetic clone of the 15 amino acid sequence of Type I collagen, involved in the binding of fibroblasts, osteoblasts and other cell types) to ABM alone in human periodontal defects.

Materials and methods: 33 patients with at least two moderate – severe periodontal osseous defects (≥3mm), 33-81 years of age, good general health, non-smokers.

After initial preparation baseline documentation was obtained. Surgical therapy consisted of reflection of full-thickness flaps, debridement of the defects, intramarrow penetration, debridement and preparation of the root surfaces. One defect was selected for the experimental group (ABM/P-15) and positive control (ABM). Graft materials were place to about the height of the remaining osseous walls, and particle sizes of the 2 graft materials were similar (250 to 420μ). Primary closure was achieved.

Recall appointments were scheduled to accomplish plaque removal every 10 days for 1 month and then followed every month for 2 months and then every 3 months. Surgical re-entry was performed at 6-7 months. Documentation included radiographs and complete perio charting related to the CEJ or restoration margin.

Results:

Significantly fewer test sites required retreatment (3 vs 13 of the control sites) since they were felt to be completely resolved. 81% of ABM/P-15 showed bone fill of 50% or more and 67% of the ABM group.

Conclusion: ABM/P-15 appears to be a useful and beneficial material for the treatment of proximal – type human periodontal defects, better than ABM alone.

Authors mention that unpublished at the time histologic data show the potential of enhancing both the bone and periodontal ligament regeneration.

Yukna 2002                    ARTICLE

P- To evaluate treatment response following the placement of ABM/P-15 bone replacement grafts utilizing the primary clinical outcomes of change in clinical attachment level, PD, and recession over a 3 year period.

M&M- 31 pts (35-65 yo) with mod-sev perio osseous defects (>3mm). Pts selected in good health, non smokers, free of disease. Intrabony defects (1-wall, 2-wall, wide 3 wall, and combination type) were treated. Narrow 3-wall, furcation defects and dehiscences were excluded. Following initial prep and re-eval, flap surgery was performed.

Bony defects were curetted and root surfaces subjected to mechanical debridement only. The bone defects were grafted with ABM/P-15, and the host flaps replaced or slightly coronally positioned. Weekly, then monthly deplaquing was performed until surgical reentry at 6 to 7 months. Patients were then followed on approximate 3-month recalls for 3 years. 25 of the original 31 patients qualified for long-term evaluation in that their ABM/P-15 treated sites did not receive any additional therapy at the time of reentry.

R: SSD in mean clinical attachment level was noted from 5.4 mm at surgery to 4.5 mm at the 6-month reentry to 3.8 mm at 3 years. There was also a decrease in mean probing depth from 5.3 mm at surgery to 3.1 mm at the 6- month reentry to 2.9 mm at 3 years. The mean gingival recession changed from +0.1 mm at surgery to 1.4 mm at the 6-month reentry to 0.9 mm at 3 years. All of these differences were at least P <0.05 from surgery to the 6-month reentry, and surgery to 3 years, but were not significant from reentry to 3 years via repeated measures analysis of variance.

C: Favorable 3-year results with ABM/P-15 suggest that it may have a beneficial effect in the long-term clinical management of infrabony defects. Further long-term randomized controlled studies are needed to better assess the role of ABM/P-15 in long-term healing of periodontal osseous defects.

Camelo 2000     porous bone mineral                     ARTICLE

Clinical, radiographic, and histologic evaluation of human periodontal defects treated with Bio-Oss and Bio-Guide

Purpose: To determine the type of healing that occurs in human intrabony periodontal defects following placement of porous bone mineral (Bio-Oss) alone or in combination with a collagen membrane (Bio-Guide)

Materials and methods

• Four anterior teeth with intrabony periodontal defects. SRP 4 weeks prior to surgery

• An amalgam restoration placed on the surface of each tooth coronal to the defect area for reference. PD and attachment levels was measured prior to surgery

• FTF, debridement, walls of the osseous defects perforated, defects filled with cancellous bone mineral Bio-Oss .

• In 2 treatment sites a collagen membrane was adapted (Bio guide). Sutures placed, Coe pak used for 2 weeks

• Postoperative examination at 7, 14, and 21 days.

• Clinical measurements repeated at 6 and 9 months

• Bloc section was taken for histologic evaluation

Results

Conclusion

• Bio-Oss and Bioguide were both biocompatible

• Bio-Oss appears to be acting as a true osteoconductive matrix

• There was new attachment formation consisting of collagen fibers inserting into new Cementum

• At 7months the collagen membrane remained intact in one specimen and partially intact in the second.

Mellonig 2000                     ARTICLE

P: To histologically evaluate in human interproximal angular osseous defects the potential of particulate cancellous bovine-derived bone xenograft to regenerate an attachment apparatus

M&M: 4 pts with at least one tooth that was going to be extracted due to advanced periodontitis and radiographic evidence of vertical bone loss were chosen. They received supragingival scaling. Occlusal adjustment and extracoronal splinting were performed. PD, recession and CAL were recorded. Pre-op radiographs were taken. At surgery, depth of osseous defect was measured, and a notch was made through the most apical extent of the calculus. Defect was debrided prior to grafting with Bio-Oss and Bio-Gide. Pts were seen weekly for first month and bi-weekly until block sections were taken 4-6 months postsurgery for histology.

R: Regeneration was observed in 3 out of 6 sites. One site healed with a long JE, but that patient smoked 2 packs/day, which may have been a contributing factor. PD reduction ranged from 4.0mm to 7.0mm and CAL gain varied from 4.0 to 6.0 mm. In one case the graft was encapsulated, while in the regeneration cases the material was surrounded by bone. The quantity of bone varied between sites as well, although this is not surprising because the morphology of the defects was quite varied. One site had abundant bone, while the other two sites did not present much bone at all.

BL: There is a 50% chance to achieve regeneration in periodontal defects using Bio-Oss.

Stavropoulos Karring 2003                    ARTICLE

Purpose: To compare treatment outcomes of infrabony defects with OFD, GTR using membrane only, GTR with biooss, and membrane w/ bioss impregnated with gentamycin

M & M: 60 pts, with at least one interproximal intrabony defect with PPD ≥7 mm and radiographic evidence of an intrabony component (IC) ≥4 mm, were, following initial therapy of OHI and SRP, had FTF reflected, area debrided and then morphology of defect was determined if 1 or 2 walled defect and is greater than 4mm deep. Defects were treated w/ either a resorbable membrane, a membrane in combination with Bio-Oss impregnated with saline, a resorbable membrane in combination with Bio-Oss impregnated with 2% gentamicin, or OFD alone.

Results: All tx modalities resulted in SS clinical improvements after 1 year.

BL: No added effect of Bio-Oss in combination with GTR on the healing of deep interproximal 1- or 2-wall, or combined 1- and 2-wall intrabony defects compared with GTR alone. Local application of gentamicin did improve the tx outcome but was found to be NSSD.
 

Cosyn 2012                    ARTICLE

P: To examine clinical and esthetic outcomes for treating intraboney defects w/ xenograft.

M&M: 84 pts were included in the study. All had intial therpy completed and presented w/ 1 or more isolated defect. Clinical and radiographic examination was completed pre and post-op. The surgical approach used the Minimally Invasive Surgical Technique (Cortellini and Tonetti 2007)- a papilla sparing incision is made with a microblade to obtain access. If access is insufficient, the incision would be extended distal one tooth. After reflecteion, granulation tissue was removed and root surfaces were debrided. Sites were grafted with Bio-oss Collagen and primary closure was obtained. SPT was performed every 3 mo for the follow-up period- 1 yr.

R: Average pre-op values of PD was 7.8 mm, CAL of 10.0 mm and defect depth of 
5.2 mm. At 1 year post-op mean PD reduction was 3.5 mm CAL gain was 3.1 mm and defect fill was 53%. Increase in mean recession was 0.3 mm. Risk factors for failure included defects with a non-supportive anatomy (OR of 10.4), plaque (OR: 14.7). Risk factors for advanced midfacial REC increase included defects with a non-supportive anatomy (OR: 58.8) and a thin-scalloped gingival biotype (OR: 76.9)

C: Regeneration utilizing minimally invasive surgery and a collagen-enriched bovine- derived xenograft demonstrated defect resolution, though soft tissue aesthetics could not always be maintained. Defects with a non-supporting anatomy may be at risk for failure and advanced midfacial recession.

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