Tooth Allografts Research Articles

United Kingdom OOKP outcomes

AbstractThe osteo‐odonto‐keratoprosthesis (OOKP) is the only option for sight restoration in patients with end‐stage ocular surface blindness in eyes with severe dryness and eyelid anomalies or defective blink. OOKP is performed as a multistage procedure, which involves buccal mucosal grafting over the eye, OOKP device construction and its impanation into the eye in sequential steps. A retrospective study was conducted at Sussex eye hospital, Brighton, and the long‐term outcomes of the OOKP cases are presented here. In total 64 patients were included, and 74 laminae were implanted, which included 60 tooth autografts, 11 tooth allografts and 3 tibial grafts. Stevens‐Johnson syndrome was the most common indication accounting for 43% (n = 7) of the cases. Glaucoma was the most common complication noted in 86% (n = 57) of the cases. Laminar resorption was noted in 67% of the laminae. At 10 years of follow‐up, 59% of the eyes had a vision better than 6/12 and 82% had a vision better than 6/60. Autograft laminae showed a survival probability of 91% over 18 years. In summary, OOKP provides excellent visual recovery and longevity of the device over the long term; nevertheless, it requires close monitoring and timely interventions to treat any complications.

Effect of donor-specific blood transfusions on allotransplanted teeth in a monkey model: Histoquantification of periodontal healing.

Pre-transplant blood transfusions have previously shown a positive effect on organ allograft survival in humans and various animal species. The aims of this study were, first, to evaluate the effect of pre-transplant donor-specific blood transfusions on periodontal healing of fully developed allotransplanted teeth in monkeys; and second, to investigate the immune response against donor antigens and to determine a possible correlation between alloimmune reactions and histopathological signs of rejection. Twenty monkeys (Cercopithecus aethiops) were divided into ten pairs with similar sizes of incisors. One monkey in each pair gave three transfusions to the other monkey with 1-week intervals. One week after the last transfusion, each pair exchanged simultaneously a central maxillary incisor and a lateral mandibular incisor. The corresponding central maxillary and mandibular lateral incisors were autotransplanted to the contralateral sockets. All teeth were treated endodontically per-operatively. Histocompatibility was evaluated by mixed lymphocyte culture before the first transfusion, while alloantibodies and cell-mediated alloresponses were measured before transfusions and at 2 and 8weeks after transplantation. All animals were sacrificed 8weeks after tooth transplantation. Serial sections of the transplanted teeth were quantified histologically. Mixed lymphocyte cultures showed positive reactions in 19 of 20 cases, indicating incompatibility. The majority of the monkeys developed antibodies towards the tooth donor. Cell-mediated cytotoxicity was negative in all monkeys. Histoquantification revealed a mean score of 70% normal periodontal ligament (PDL) in autotransplanted teeth, with 5% ankylosis. The allografts had a mean score of 17% normal PDL and 63% ankylosis, with no significant influence of transfusion. However, in the mandibular grafts, a tendency towards a positive transfusion effect was seen. Donor-specific blood transfusion did not reduce ankylosis in tooth allografts. The healing of mandibular incisor tooth allografts was improved, but not that of maxillary incisors. Donor-specific antibodies showed no effect on the survival of allograft PDL.

Clinical study of laminar resorption: Part 1 – Factors affecting laminar resorption

PurposeTo analyse the factors affecting laminar resorption in the UK osteo-odonto-keratoprosthesis (OOKP) cohort and present a detailed review. MethodsA retrospective review of the case records of the patients who underwent OOKP between 1996 and 2014 was performed at the Sussex Eye Hospital in Brighton, UK. ResultsSixty-four patients (25 females and 39 males) were included, and 74 laminae were implanted consisting of 3 tibial grafts, 11 tooth allografts and 60 tooth autografts. In total, 69% (n = 51) showed resorption. Non-smokers had better oral health compared to smokers (71% vs 50%, respectively). Poor oral health was strongly associated with poor quality dentition and edentulism (p < 0.001). The laminar thickness and waiting for the time between stages 1 and 2 surgeries did not show significant influence on the onset and progression of resorption. From the Cox multivariate analysis for autografts, smoking, age and gender were not associated with a statistically significant difference in the rates of resorption. The maximum number of laminae with resorption belonged to Stevens-Johnson syndrome patients (n = 32 or 43%). ConclusionsTwo-thirds of the cases of resorption were detected in the first three years of OOKP, and the maximum were noted in the first year of follow up (40%). The laminar thickness did not influence the post-operative onset and progression of resorption. The presence of resorption after stage 1 did not show a measurable effect on the onset and progression of post-stage 2 resorption.

The Osteo-Odonto-Keratoprosthesis (OOKP)

The osteo-odonto-keratoprosthesis (OOKP), although described over 40 years ago, remains the keratoprosthesis of choice for end-stage corneal blindness not amenable to penetrating keratoplasty. It is particularly resilient to a hostile environment such as the dry keratinized eye resulting from severe Stevens-Johnson syndrome, ocular cicatricial pemphigoid, trachoma, and chemical injury. Its rigid optical cylinder gives excellent image resolution and quality. The desirable properties of the theoretical ideal keratoprosthesis is described. The indications, contraindications, and patient assessment (eye, tooth, buccal mucosa, psychology) for OOKP surgery are described. The surgical and anaesthetic techniques are described. Follow-up is life-long in order to detect and treat complications, which include oral, oculoplastic, glaucoma, vitreo-retinal complications and extrusion of the device. Resorption of the osteo-odonto-lamina is responsible for extrusion, and this is more pronounced in tooth allografts. Regular imaging with spiral-CT or electron beam tomography can help detect bone and dentine loss. The optical cylinder design is discussed. Preliminary work towards the development of a synthetic OOKP analogue is described. Finally, we describe how to set up an OOKP national referral center.

Serum antibody response to mature tooth allografts in mice.

Mature mouse molar teeth were transplanted to the tibial shaft medulla across an H-2 plus multiple non-H-2 histocompatibility barrier. Over the 35-day experimental period, low levels of complement-fixing antibody were detected in the serum of recipients. Antibody was distributed over two peak periods, 6 to 11 days and 21 to 27 days after transplantation, with IgM apparently preceding IgG production.

Serum and cell-mediated cytotoxicity after primary and secondary orthotopic tooth transplants among RhLA-paired rhesus monkeys.

Twenty-six rhesus monkeys were paired on the basis of RhLA serologically defined (SD) antigens and then mixed lymphocyte cultures (MLCs) were performed for each donor-recipient combination. All but one monkey responded positively to its partner in MLC. In vitro assays for complement-dependent antibody-mediated cytotoxicity (CDC) and lymphocyte-mediated cytotoxicity (LMC) were performed before and after each of two separate orthotopic tooth transplants for each recipient. There was no detectable CDC or LMC before tooth transplantation. The maxillary right central incisors were exchanged between paired monkeys and 60 days later the left maxillary central incisors were transplanted. After the first tooth allograft, there was very little CDC activity in any recipient and only one matched group showed any remarkable LMC activity. However, after the second tooth transplant there was a very clear CDC response in the majority of monkeys. The LMC activity remained low after retransplantation. There did not seem to be any consistent relationship between RhLA match and in vitro cytotoxicity. The results indicate that tooth allografts are weak immunogens but they do evoke humoral immunity after retransplantation. The biological relevance of these serum antibodies remains to be determined.

Antibodies to Tooth Allografts in H-2 Matched Mice

Teeth were transplanted among mice which represented the best match possible between unrelated humans. Sera were examined for their ability to kill donor cells with the help of complement, to trigger complement-independent, cell-mediated cytolysis, and to agglutinate RBC. All responses were weak, but rejection correlated best with antibody-dependent cytolysis.

Tooth Allografts Fail to Stimulate Immunologic Memory in Mice

Tooth transplants should not preclude future transplants in the recipient. In this study teeth failed to stimulate immunologic memory in weakly disparate mice. The teeth did carry transplantation antigens and were rejected after second-set skin grafts. The teeth probably enhanced their own survival through some immunoregulatory mechanism.

The immunogenicity of tooth allografts in rats

The immunogenicity of tooth allografts in rats

The immunogenicity of tooth allografts in rats.

Orthotopic and heterotopic tooth allografts stimulated the production of alloantibodies in rats incompatible at the major histocompatibility locus. The immunogenicity of whole tooth grafts was slightly diminished but not eliminated by sealing the pulp cavity prior to grafting. Suspensions of dentine in saline elicited alloantibody formation on i.p. injection into allogeneic hosts. Orthotopic tooth allografts, but not heterotopic grafts, were as effective as skin allografts at stimulating second set rejection of challenging skin grafts. Orthotopic tooth allografts were indistinguishable from syngeneic grafts on histological examination over the period 1-6 weeks after grafting. The occurrence of alloantibody formation after tooth grafting was capricious, and this, combined with the histological difficulty of distinguishing syngeneic from allogeneic grafts, and also the differing capacity of orthotopic and heterotopic tooth allografts to provoke accelerated skin grafts rejection, probably accounts for some of the differences of opinion expressed previously on the immunogenicity of grafted teeth.

Orthotopic transplantation of tooth buds among histoincompatible mice.

The survival of tooth buds transplanted orthotopically to juvenile inbred mice was found to be dependent upon the allelic combination as well as the nature of the histocompatibility gene differences between donor and recipient. Acute rejection of tooth allografts in 7–13 days regularly occurred across the following incompatibilities: (1) H-2a ← H-2b plus multiple non-H-2 disparities; (2) H-2a ← H-2b only; (3) H-4b, H-11a ← H-4aH-11a only. By contrast, the reciprocal double disparity H-4a, H-11b ← H-4b, H-11a yielded greatly prolonged allograft survival. Moreover, the reaction patterns of orthotopic tooth buds versus skin allografts suggest the need for new concepts of antigenic mass and histocompatibility gene expression. When only weak immunogenetic differences of appropriate allelic combination existed, tooth buds were clearly able to withstand antagonistic host reactions. This appeared to involve differential susceptibilities of donor cell types to immunological mediators. Possible bases for the preferential survival of fibrous tissue in tooth bud allografts are considered.

Evidence of immune response to orthotopic tooth allografts in Syrian hamsters.

Evidence of immune response to orthotopic tooth allografts in Syrian hamsters.

Experimental allogeneic tooth transplantation in the rhesus monkey.

Forty-eight tooth allografts were studied histologically and radiographically four days to 13 months after transplantation. The pulp and periodontal ligament degenerated and appeared to be replaced by host tissues. The relationship of attached fibers or uncalcified cells of hard tissues to allograft immunity and the similarity of tooth allografts to other tissue allografts were discussed.