Titanium as a biomaterial for ossicular replacement: results after implantation in the middle ear of the rabbit

The middle ear poses unique challenges when finding suitable materials for ossicular reconstruction, primarily because of its link to the external environment via the eustachian tube and, hence, its greater exposure to infectious agents. In this study, the biocompatability of titanium was examined in the middle ear of rabbits by using light and scanning electron microscopy. Implants were placed as middle ear prostheses or as free implants. These were inspected at 28 days, 84 days, 168 days, 336 days and 504 days following implantation for mucosal coverage, percent epithelization and any sign of foreign-body reaction. After 28 days, the prostheses were covered by regular mucosa. Although a majority of the free implants took up to 336 days for complete epithelialization, some of the free implants were not epithelialized even at day 504. There were no inflammatory cells observed on the surface of the material, nor were unusual amounts of fibrous tissue seen. In addition, the titanium material exhibited an affinity toward bone. The results of this animal experiment indicate that titanium is a favorable material for ossicular replacement prostheses. Received: 20 January 1998 / Accepted: 19 March 1998     

Tissue response to Plasti-Pore and Proplast otologic implants in the middle ears of cats

Plasti-Pore (high density polyethylene) and Proplast (polytetrafluoroethylene-carbon fiber composite) are porous materials that have been employed for the fabrication of ossicular replacement prostheses. Despite many years of clinical experience with these otologic implants, questions remain regarding the tissue response elicited by these materials in the middle ear. The objective of this study was to evaluate histologically the tissue response to Plasti-Pore and Proplast implants in the middle ears of cats through one year of implantation. Plasti-Pore and Proplast total ossicular replacement prostheses, trimmed to "T" shapes, were inserted in fourteen cats, replacing the superstructure of the stapes. One Plasti-Pore and one Proplast implant were implanted in each animal. Cats were killed after two weeks, one, three, and six months, and one year. The histologic response to the Plasti-Pore and Proplast implants was similar. A fibrous capsule contained within a flattened epithelial cell sheath enveloped both types of implants. The mucosa enveloping the devices was continuous with the lining of the tympanic cavity and served to stabilize the implants. Fibrous tissue from the capsule infiltrated larger surface pores. Multinucleated giant cells and macrophages were the predominant cell types in the porosity of both types of implants. The relatively small pores of the devices did not appear to be able to accommodate both the phagocytic cells, which were responding to the particulate features of the materials, and fibrous tissue.     

Histological evaluation of novel ossicular chain replacement prostheses: an animal study in rabbits

CONCLUSION: The improved biocompatibility of Bioverit II coated with a nanostructured surface shows promising qualities for use in human reconstructive middle ear surgery. In the case of chitosan-hydroxyapatite composite prostheses, further investigations regarding composition of the material, degree of purity and design are necessary before clinical application. OBJECTIVE: The selection of optimal materials for reconstructive middle ear surgery continues to be a problem. In the present study novel materials were tested as total ossicular replacement prostheses (TORPs) in an animal model. MATERIALS AND METHODS: Bioverit II coated with a nanostructured surface and chitosan-hydroxyapatite composites were placed in the middle ear of 40 rabbits. Uncoated Bioverit II was used as control. After an implantation period of 28, 84 or 300 days petrous bones were extracted, embedded in epoxy resin and examined by light microscopy. RESULTS: Uncoated and coated Bioverit prostheses revealed a mucosal coverage and a little osseogenic response after 28 days. The results of the coated Bioverit prostheses slightly surpassed those of the plain prostheses. Chitosan-hydroxyapatite composite prostheses were mostly found to be dislocated after 28 days. Formations of granulation tissue and fibrotic capsules were observed around these implants. This reaction could be caused by the instability of the composite material or may be due to impurities present in the chitosan.     

Histopathological studies in the long-term evaluation of Plastipore prostheses

Polyethylene sponge (Plastipore TM) prostheses were clinically implanted in the middle ear for periods varying from 2 weeks to 6 years. Revision surgery allowed removal of 98 of these prostheses for histological examinations. Local foreign body reactions and/or microscopic breakdown of the polyethylene were found to varying degrees in 95 of the 98 prostheses. The remaining 3 prostheses showed only fibrous tissue ingrowth without other changes. We compared the histopathology present with the length of time of implantation, and found that the changes noted were more frequent and marked in those prostheses implanted for long periods of time.     

Histopathological studies in the long-term evaluation of Plastipore prostheses

Summary Polyethylene sponge (Plastipore TM) prostheses were clinically implanted in the middle ear for periods varying from 2 weeks to 6 years. Revision surgery allowed removal of 98 of these prostheses for histological examinations. Local foreign body reactions and/or microscopic breakdown of the polyethylene were found to varying degrees in 95 of the 98 prostheses. The remaining 3 prostheses showed only fibrous tissue ingrowth without other changes. We compared the histopathology present with the length of time of implantation, and found that the changes noted were more frequent and marked in those prostheses implanted for long periods of time.     

Proplast and Plastipore*

Sixteen Proplast and 52 Plastipore prostheses, removed at revision surgery, have been examined histologically and the findings illustrated. The macroscopic appearance of the prostheses was preserved. Fibrous tissue capsule formation was common. It has been expected that the prostheses will be invaded by fibrous tissue and thereby stabilized. Fibrous tissue ingrowth was consistently seen in Proplast but not Plastipore prostheses. Multinucleared foreign body giant cells were present in large numbers in both types. There was histological evidence of breakdown of the prostheses.     

Surgical pathology of middle ear implants

During the past 15 years a series of 25 middle ear implants was removed at the time of revision surgery and prepared for histological study. These revision operations were performed because of failure to control the disease and/or persistent or recurring hearing loss. The ossicular and cortical bone autografts showed similar behavior in that they underwent creeping substitution with vitalized bone in amounts varying from 0% to 83%. There was no correlation to duration of implantation. The four cartilage grafts, on macroscopic evaluation, showed a loss of rigidity. Two of three cartilage autografts showed a high rate of survival of chondrocytes. The two TORP prostheses showed extensive invasion of their porous spaces with foreign body giant cells. One of the latter, implanted for over four years showed fibrous replacement of plastic material. The two polyethylene tubes showed intraluminal foreign body reaction and new bone formation.     

Biomaterials for implantable middle ear hearing devices

The use of biomaterials to ameliorate the effects of diseases dates back centuries to the ancient Greeks and Chinese. In the twentieth century, the use of synthetic and natural materials rapidly increased as clinicians developed problem-solving strategies. From replacement prostheses, to structural polymers, to the controlled release of engineered proteins into the body, to the present-day tissue engineering, biomaterials have transformed medicine. The ear is no exception. Various alloplastic and homograft biomaterials have been used to restore hearing with ossicular replacement prostheses, cochlear implants, and most recently, implantable middle ear devices. This article updates an earlier review of biomaterials used in implantable middle ear devices and focuses on biomaterials used in implantable middle ear devices currently under development or in clinical trials.     

Histopathology of ossicular grafts and implants in chronic otitis media

OBJECTIVES: We describe the histopathology of ossicular grafts and implants so as to provide insight into factors that may influence functional results after surgery for chronic otitis media. METHODS: Histopathologic observations were made on 56 cases: 50 surgical specimens and 6 temporal bone cases in which the graft was sectioned in situ. RESULTS AND CONCLUSIONS: Autogenous malleus, incus, and cortical bone grafts behaved in a similar manner and maintained their morphological size, shape, and contour for extended periods of time, at least up to 30 years. These histopathologic observations support the continued use of autograft ossicular and cortical bone grafts for middle ear reconstruction. Cartilage grafts developed chondromalacia with resulting loss of stiffness and showed a tendency to undergo resorption. Synthetic prostheses made of porous plastic (Plastipore, Polycel) elicited foreign body giant cell reactions with various degrees of biodegradation of the implants. Prostheses made of hydroxyapatite and Bioglass were enveloped by a lining of connective tissue and mucosal epithelium. The Bioglass material was broken down into small fragments and partially resorbed by a host response within the middle ear. These results warrant caution in the use of prostheses made of porous plastic or Bioglass.     

Are titanium implants superior to gold implants in the tympanic cavity?

BACKGROUND: Gold implants in reconstructive surgery of the middle ear have proved to work sufficiently: That applies to tympanic cavity conditions without signs of chronic inflammation as also to the bacterially infected middle ear. For some years titanium implants are also in the use and established as well. The biocompatibility of titanium, the clinical and the audiological results are satisfactory. When using gold-prostheses in stapes surgery however, the still unsolved problem of occasional deafness has to be considered. PATIENTS: The clinical and functional results of middle ear surgery were examined retrospectively. There was no preselection of patients. 53 patients underwent middle ear surgery with titanium prostheses, 42 patients with gold prostheses. RESULTS: Due to their material properties and due to their delicate shape titanium prostheses (PORP, TORP) can be inserted into the tympanic cavity more simply and with better fit. The audiological results of gold and titanium prostheses are comparable. The extruding rate of the gold prostheses is substantial, whereas the extruding rate of titanium is negligible. CONCLUSION: The functional results of both materials are comparable. Due to the high extruding rates of gold prostheses titanium is clearly superior.     

Titanium as a material for ossicular replacement - basic aspects and clinical application

BACKGROUND: The use of titanium as a biomaterial in ossicular chain reconstruction is increasing. The situation for integration of biomaterials is more difficult in the semiopen implantation site middle ear than in other parts of the body. Important for integration is the contact of the biomaterial's surface toward proteins. Studies of the integration in living tissue still have to be performed in animal experiments. Morphological examinations of explanted prostheses after clinical use complete the picture of an ossicular replacement material. METHODS: Preclinical studies where performed to compare the adsorption behaviour of titanium, stainless steel and aluminum oxide toward radioactive marked albumin and native collagen type I. An animal model in the rabbit was performed to study the integration of titanium in the middle ear morphologically. Middle ear prostheses removed during revision surgery were studied as well. RESULTS: Titanium showed an adsorption amount of 360 microgram/cm(2), stainless steel of 230 microgram/cm(2) and aluminum oxide of 500 microgram/cm(2) out of an albumin solution of 400 mg/ml. Comparing desorption the mean loss was 16 % for titanium, 21 % for stainless steel and 23 % for aluminium oxide. Reassembled collagen fibrils could be detected after adsorption in collagen type I solution by means of scanning electron microscopy. Morphological studies in animal experiments showed regular healing after implantation. Explanted prostheses from humans did not show any cellular signs of repulsion. CONCLUSION: The results of preclinical studies and clinical use demonstrate titanium as a useful material for ossicular reconstruction in middle ear surgery.     

Materialien zur Rekonstruktion des Schalleitungsapparats

To rehabilitate most cases of conductive hearing loss closure of ear drum perforations and rebuilding of the ossicular chain can be performed. Due to the great number of biocompatible bone substitute materials available it is occasionally difficult for the surgeon to choose the most favorable substitute. Autogenous structures (ossicles, cortical bone, cartilage) and allogenous tissues (ossicles, cortical bone, cartilage, dentin) are possible bone replacement materials. Xenogenic tissue is currently not used in middle ear surgery. Ionomer cement is a hybrid material for replacement of bone but does not fit direct classification of the various classes of alloplastic materials in current use: that is, metals (gold, steel wire, platinum, titanium), plastics (polyethylene, polytetrafluorethylene) and ceramics (ceramic oxide, carbon, calcium-phosphate ceramic, vitreous ceramic). For restoration of the sound conductive apparatus preference is given to autogenous ossicles because cortical bone is resorbed and cartilage weakens over time. Most surgeons do not use allogenous tissue, because of the possible transmission of such infectious disease as immunodeficiency syndrome or Creutzfeldt-Jakob disease. Only dentin deserves special attention as a possible bone substitute in the middle ear because its form can be preserved during sterilization. Based on the observations available to date, it becomes apparent that titanium implants hold greater promise than gold. Form-stable synthetic materials are not generally recommended due to foreign body reactions which have been confirmed by many investigators. Ceramic materials (e.g. ceramic oxide, carbon, calcium-phosphate ceramic, glass ceramic) are well tolerated in the middle ear and have also proved to be useful over time. Hybrid bone substitute ionomer cement is easily workable and well integrated, showing a good functional outcome. For many years good results in otosclerosis surgery have been achieved with a prosthesis made of platinum-wire and Teflon. Short-term follow-up periods hold great promise with pistons made of gold. Autogenous ossicles, ionomer cement and recently titanium protheses--as far as usable--are employed by the author for reconstructing the middle ear. For the time being platinum-Teflon prostheses and gold are used in otosclerosis surgery.     

Soft tissue reaction to ceramic ossicular replacement prosthesis

Soft-tissue reaction to ceramic ossicular replacement prostheses (CORP) has been evaluated histologically in rabbits and humans. One week after implantation, severe inflammatory and foreign body reaction was observed in the fibrous connective tissue surrounding the prosthesis. Though some inflammatory response was seen after one month, after three months the CORP was surrounded by a layer of fibrous connective tissue without any foreign body giant cell, histiocyte or inflammatory cell infiltration. Our satisfactory clinical results in humans without placing a cartilage between the CORP and the fascia graft may be due to the excellent soft-tissue compatibility of CORP, as demonstrated in this study.     

The use of Proplast in experimental middle ear surgery

The results of the use of Proplast, a new alloplastic material, in experimental middle ear surgery are described. This material was tested for cavity obliteration, closure of bony defects and as a columella between the tympanic membrane and the medial wall of the middle ear. Proplast was well tolerated in the middle ear cavity even in cases with inflammation of the middle ear. The implants were integrated within the recipient tissue by fibrous ingrowth occurring within one week. Bony ingrowth was observed in those cases where the implant contacted the bony wall within 3 weeks. Proplast which supported the tympanic membrane was infiltrated by fibrous tissue and incorporated in the lamina propria. No significant side effects were observed in a 6-month follow-up period although a possible influence on bone remodelling could not be fully excluded.     

Tissue reactions to glass ceramics in the middle ear*

The bioactive glass ceramic ‘Ceravital’ was used to fashion protheses for the replacement of various ossicles in the middle ear. They were tested in 70 rabbit ears, where they were accepted in osseous areas without formation of surrounding fibrous tissue. Histological examinations regularly showed an osseous bond with the surrounding bony tissue. Mucous membrane covered these ossicular chain prostheses and showed no evidence of inflammatory reactions. Glass ceramic implants were also used to reconstruct the ossicular chain and the posterior wall of the outer ear canal in 100 patients. The functional results were satisfactory in all cases.     

In vitro reconstruction of a three-dimensional middle ear mucosal organ and its in vivo transplantation

CONCLUSIONS: These experimental findings suggest the feasibility of artificial middle ear mucosa grafting as an effective treatment for achieving mucosal regeneration after middle ear surgery. OBJECTIVES: Postoperative mucosal regeneration of tympanic cavity and mastoid cavity is of great importance after middle ear surgery. We reconstructed in vitro a three-dimensional middle ear mucosal organ, and assessed its feasibility for regenerative medicine of middle ear-related diseases. MATERIALS AND METHODS: Epithelial cells and fibroblasts were isolated from the middle ear mucosa of rats and propagated by subculturing. An artificial middle ear mucosal organ was reconstructed by overlaying the middle ear epithelial cells on three-dimensional lattices of a collagen gel that had been repopulated with the fibroblasts. In addition, the artificial organ was implanted in the middle ear cavity of rats. RESULTS: The artificial middle ear mucosa consisted of the single layer of epithelial cells, the basal membrane, and the underlying connective tissue. Electron microscopy revealed the presence of tight junctions and adherence junctions on the apical side, and adhesion complexes made of desmosomes. The reconstituted mucosa expressed genes of mucin, strongly suggesting that the artificial middle ear mucosa was capable of secreting mucus proteins. The DiI-labeled artificial middle ear mucosa implanted into the middle ear cavity was well engrafted and associated with host tissues.     

Chronic ear pathology in a model of neonatal amniotic fluid ear inoculation.

Human histopathologic studies have demonstrated that amniotic fluid cellular contents, keratinized squamous epithelial cells and lanugo hair, induce an intense inflammatory reaction including granulation tissue in the neonatal temporal bone. To investigate this reaction over a prolonged period, an animal model was studied. An aliquot of sterilized autologous hair and keratinized epithelial cells was placed into 14 gerbil bullae; saline was used as a contralateral control. The animals were sacrificed at intervals up to 6 months and the temporal bones were studied by light microscopy. All animals demonstrated nonpurulent inflammatory changes on the experimental side including granulation tissue, osteoneogenesis, tympanosclerosis, and cholesteatoma; the control side demonstrated minimal middle ear changes. We conclude that in this model autologous keratinized tissue provokes a foreign body response similar to the granulation tissue observed in human infants and, further, that over a prolonged period the middle ear demonstrates more severe pathologic consequences.     

Structure and origin of middle ear corpuscles

The incidence, origin, structure and composition of middle ear corpuscles (MEC) were studied by dissection microscopy, by special stains and immunocytochemistry of histological sections and by transmission electron microscopy. MEC are formed within fibrous bands derived from transparent fibrous sheets which appear mainly in the mastoid antrum in the middle-aged and elderly. MEC are covered by a layer of epithelial cells with a normal basal lamina, and are largely composed of concentric layers of collagen which display alternating positive and negative birefringence. Pulmonary and prostatic corpora amylacea show a similar light microscopical structure and age relationship, but contain amyloid. It is suggested that MEC and the other bodies may be organized foci of epithelial basement membrane expansion perhaps derived from an in vivo counterpart of the ‘domes’ seen in vitro in some monolayer epithelial cultures.     

New alloplastic tympanic membrane material.

For patients with a totally empty middle ear a total alloplastic middle ear prosthesis (TAM) has been developed consisting of a macroporous hydroxyapatite canal-wall segment as a foundation system from which a dense hydroxyapatite ossicular chain is suspended. To connect the ossicular chain, we developed an alloplastic tympanic membrane made from a polymer. Light microscopy, morphometry, and autoradiography as well as various electron microscopy techniques were used in this study to evaluate the biocompatibility of Polyactive, a polyether polyester copolymer, after implantation in the rat middle ear. After between 2 and 4 weeks, implants were completely covered by tympanic-membrane epidermis and epithelium. Polyactive provoked a mild foreign-body reaction, showed a degradation rate of 54 percent after 1 year, and was nontoxic. Growth of fibrous tissue and bone into Polyactive copolymer indicated appropriate implant fixation by mechanical interlocking. The fixation of Polyactive by ingrowth of bone is promising, not only in terms of the amount of bone but also in terms of the bone/polymer interface. The latter is indicative of bonding osteogenesis in a way similar to that reported for hydroxyapatite implants. The results of this study showed that Polyactive copolymer is suitable as a degradable alloplastic tympanic membrane, both as a temporary scaffolding for the repair of tympanic membrane perforations and as a tympanic membrane in the TAM.     

Tympanoplasty with hybrid prostheses

BACKGROUND: The retrospective study reviews the hearing results of partial and total ossicular replacement plasties with prostheses composed of a hydroxylapatite head and a trimmable shaft. PATIENTS AND METHODS: 71 patients underwent tympanoplasty type III between January 1996 and January 2002. The partial (PORP) (55 patients) and total ossicular replacement prostheses (TORP) (16 patients) were a composition of a hydroxylapatite head and a trimmable hydroxylapatite-polyethylene composite shaft (HAPEX ). Hearing results were evaluated according to the guidelines of the Committee on Hearing and Equilibrium. RESULTS: In cases with a PORP the residual air-bone gap could be reduced to < or = 20 dB in 73% of the patients. The mean air-bone gap improved from 28 dB preoperatively to 17 dB postoperatively. In cases with a TORP the residual air-bone gap could be reduced to < or = 20 dB in 62% of the patients. The mean air-bone gap improved from 32 dB preoperatively to 20 dB postoperatively. CONCLUSIONS: The hearing results with prostheses composed of a hydroxylapatite head and a trimmable shaft are good and comparable to the results of authors using other synthetic ossicular prostheses. These prostheses are time-saving because the trimmable shaft can be quickly cut and shortened to an individual length.