- Open Access
The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence
BMC Medicine volume 10, Article number: 81 (2012)
Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness.
Treatment of large bone defects represents a great challenge, as bone regeneration is required in large quantity and may be beyond the potential for self-healing. Large bone defects include segmental or large cortical defects created by trauma, infection, tumor resection, aseptic loosening around implants and skeletal abnormalities [1, 2]. Critical size defect (CSD) is defined as the defect with the minimum length that cannot be spontaneously bridged leading to non-union [2, 3]. Such defects are generally accepted to be ≥ 1.5 to 2 times the diameter of the long bone diaphysis, but they vary according to the host and the bone .
Although many methods for bone reconstruction exist, they all have specific indications and limitations. Established methods are distraction osteogenesis and bone transport, or bone grafting, including autologous bone grafts, bone marrow aspirate, allografts, bone substitutes or growth factors [4–8]. Furthermore, the concept of an induced-membrane represents another strategy for bone regeneration and particularly in cases of large bone defects secondary to trauma, infection or tumor excision. This method involves a two-stage procedure, where a 'biological' membrane is induced as a foreign body response after application of a cement spacer at the first stage, acting as a 'chamber' for the insertion of autologous bone-graft at the second stage [9–11]. It has been shown that this induced membrane possesses osteoinductive, osteogenic and angiogenic properties and several clinical studies have demonstrated satisfactory results [9, 12]. Finally, the concept of Guided Bone Regeneration (GBR) using a bioabsorbable or non-resorbable membrane that acts as a barrier to prevent soft-tissue invasion into the defect and forms a 'chamber' to 'guide' the bone regeneration process [13–15] is also used for bone reconstruction.
Historically, the concept of GBR has been used in experimental reconstructive surgery since the mid-1950s, for spinal fusion  and maxillofacial reconstruction [17, 18]. The initial hypothesis was that different cellular components in the tissue have varying rates of migration into a wound area during healing and that a mechanical hindrance would exclude the invasion of inhibiting substances, such as fibroblasts . Preliminary studies showed that the use of a non-resorbable membrane as a mechanical barrier resulted in complete healing of the bone defect in vivo , and collagen membranes prevented the apical migration of epithelium and supported new connective tissue attachment and tissue regeneration . The regeneration process occurring within the barrier membrane involves angiogenesis and migration of osteogenic cells from the periphery towards the center to create a well-vascularized granulation tissue. Initial organization of the blood clot is followed by vascular ingrowth and woven bone deposition, subsequent lamellar bone formation and finally remodeling, resembling bone growth [22, 23]. When ingrowth of bone marrow into the bone defect was hindered or delayed, regeneration of mineralized bone was also delayed . However, in large defects, bone formation occurs only to the marginal stable zone with a central zone of disorganized loose connective tissue, and, therefore, additional use of bone-graft materials is required in these cases, with the graft acting as a scaffold for osteoconduction and as a source of osteogenic and osteoinductive substances for lamellar bone formation .
Types of barrier membranes, their basic characteristics and specific considerations
Although different non-resorbable and bioresorbable barrier membranes have been developed and their use has been extensively investigated, research is ongoing to develop the 'ideal' membrane for clinical applications. The basic characteristics of these membranes are biocompatibility, cell-occlusiveness, space-making, tissue integration, and clinical manageability [15, 25].
Non-resorbable membranes and especially expanded-polytetrafuoroethylene (e-PTFE, Teflon) have been extensively studied . They are biocompatible and maintain their structural integrity during implantation. They have superior space-maintaining properties and capacity for cell occlusion than degradable membranes, as the latter tend to collapse depending on the size of the defect . Other non-resorbable membranes are titanium reinforced ePTFE, high-density-PTFE, or titanium mesh mainly used in oral and maxillofacial surgery  (Table 1). Semipermeable ePTFE is more effective than the high-density ePTFE with respect to bone regeneration . For bone regeneration of large segmental bone defects, the cylindrical titanium mesh cage has been used as a scaffold with satisfactory preliminary results . However, a second surgical procedure is required for removal, which represents a limitation and involves a potential risk to the newly regenerated tissues . Finally, membrane exposure is frequent, increasing the risk of secondary infection [31, 32].
Bioresorbable membranes have been developed to avoid the need for surgical removal. Such membranes have been extensively studied, mainly in animals but also in humans in maxillofacial, regenerative periodontal, and neuro-surgery [14, 33–38]. Recently, commercially available bioresorbable membranes have also been used for reconstruction of long bone defects in the clinical setting. It has been shown that they enhance bone healing, especially in cases with bone defects > 4 to 5 cm or with significant associated soft-tissue loss, where autologous bone grafting alone is not recommended due to risk of resorption , and they also secure the grafting material . There are two broad categories of bioresorbable membranes: the natural and the synthetic membranes. Natural membranes are made of collagen or chitosan, whereas synthetic products are made of aliphatic polyesters, primarily poly(L-lactide) (PLLA) and poly(L-lactide-co-glycolide) (PLGA) co-polymers . Overall, their advantages are: 1) they allow for a single-step procedure, 2) the shape and volume of the regenerated bone can be predefined-prefabricated, 3) they are radiolucent allowing imaging, and 4) their bioresorption eliminates potential effects of stress shielding of the regenerated bone. Conversely, there is variability and lack of control over the rate of membrane resorption, which is influenced by factors such as the local pH and material composition. A summary of the main characteristics, advantages and disadvantages of the different bioresorbable membranes is presented in Table 1 [13, 21, 31, 38, 40–59]. Currently, mainly PLLA membranes are available for clinical use in orthopedic surgery; whereas PLLA, collagen and ePTFE membranes are used for GBR in maxillofacial, dental and neuro- surgery.
Although a number of barrier membranes are already being used in clinical practice, novel membranes have been developed in an effort to overcome the limitations of the currently used membranes. Such novel membranes include alginate membranes, new degradable co-polymers, hybrid or nanofibrous membranes, as well as amniotic membranes. They are summarized in Table 1 [60–75]. Ongoing research is evaluating these novel membranes, aiming to establish an 'ideal' membrane for bone regeneration with optimized characteristics in terms of biocompatibility, space-making, tissue integration and clinical manageability for maximum clinical efficacy and safety.
The role of porosity and topography of the barrier membranes
The pore size of the barrier membrane is very important in order to prevent excessive penetration of fibrous tissue into the bone defect (soft tissue ingrowth) but to allow neovascularization and bone formation. Differences in the intensity of bone regeneration were observed depending on the pore size . Pores in excess of 100 μm are required for the rapid penetration of highly vascular connective tissue, and small pores tend to become filled with more avascular tissue , as they are inadequate for penetration of capillaries . A pore size of 50 to 100 μm allows bone ingrowth, but size greater than 150 μm is required for osteon formation [79, 80]. A recent animal study showed that macroporous membranes facilitated greater bone regeneration compared to microporous membranes and prevented significant soft-tissue ingrowth . Further research should be directed to identify the critical pore size, since an increase in pore size may result in decreased mechanical properties. A multilayer scaffold has been suggested to achieve suitable mechanical properties and porosity and mimic the structure of cancellous and cortical bone . In addition to the porosity, the tri-dimensional topography of the membrane with interconnecting pores and channels is also important, as it can alter the cell occlusion properties and the biologic response of different cell types to the membrane .
The role of soft tissue ingrowth
Although barrier membranes are used to prevent soft-tissue invasion, a thin layer of soft-tissue ingrowth (up to 1 mm thickness) can be formed under the membrane, overlying the regenerated bone [84–86]. This may be secondary to shrinkage of the initial blood clot under the membrane, entrapment of air or membrane micromovements. Currently, it is not known if this soft-tissue layer under the membrane undergoes mineralization if left for a long period. Some studies reported this tissue-layer was a periosteum-like tissue, and others reported it to be fibrous tissue  but its clinical implications are unknown.
The role of mechanical stability
It is known that micromovements between bone and any implanted material prevent bone formation, resulting in the development of fibrous tissue [87, 88]. Adequate stability and minimal stress are required to allow the early tissue that infiltrates through the pores to differentiate into bone by direct or appositional bone formation . Bone formation can occur within porous materials even with limited initial movement provided the site is highly vascular and local inflammatory reaction is minimal . New vascular network formation, which is a prerequisite for bone formation, is also highly sensitive to mechanical conditions with delayed mechanical loading significantly enhancing bone formation and stimulating vascular remodelling by increasing the number of large vessels and decreasing the number of small vessels . Therefore, optimal stability should be provided in terms of the attachment of the membrane itself, since most bioresorbable membranes are flexible and they cannot be applied without additional fixation as well as the type of fixation of the bone defect . To maximize stability of the membrane, the use of membrane-fixing pins has been suggested. It has been observed that bone formation is significantly enhanced when the resorbable membrane is tightly attached and immobilized to the bone surface . Regarding the effect of the type of additional fixation to the process of bone formation, it is known that intermediate tissues, such as fibrous tissue, cartilage and woven bone, precede final bone formation, with the mechanical loading affecting the regeneration process and different stress distribution favoring or inhibiting differentiation of particular tissue phenotypes . High shear strain and fluid flows stimulate fibrous tissue formation, whereas lower levels stimulate formation of cartilage, and even lower levels favor ossification. It has been demonstrated in vivo that there is more rapid and more organized new bone formation in rigidly fixed defects with plate osteosynthesis, covered with a resorbable collagen membrane, compared to non-rigidly fixed defects .
As research on the field of bone regeneration is ongoing and the evidence is expanding, we aimed to summarize the current experimental and clinical research on the use of barrier membranes for restoration of bone defects and focus on maxillofacial and orthopedic applications. We searched the PubMed Medline and Ovid Medline databases, from 1991 to 2011, to retrieve all relevant articles reporting on the use of absorbable and/or non-absorbable membranes for bone regeneration in animal and clinical studies. Different combinations of searching terms were used including: membrane/bone regeneration/long bone/bone defect/segmental bone defect/segmental mandibular defect/mandibular defect. The search was restricted to studies published in English. We analyzed all preclinical studies using established animal models to evaluate barrier membranes for bone regeneration of segmental, large and critical-sized mandibular or long-bone defects, in which bone regeneration was documented and assessed using radiological or biomechanical and/or histological analysis. Regarding the clinical studies, all papers reporting on the clinical use of barrier membranes were analyzed.
Tables 2 to 5 summarize the preclinical studies with non-absorbable or bioabsorbable membranes. There were 23 animal studies reporting on the use of membranes in maxillo-facial surgery for reconstruction of segmental or critical mandibular defects using small or large animal models (Table 2, 15 studies [31, 34, 54, 63, 64, 94–103] and Table 3, 8 studies [22, 104–110], respectively). Overall, the membrane-treated groups showed improved bone formation within the mandibular defects compared to the non-treated animals [22, 96, 98]. Differences in the rate of bone regeneration and the inflammatory response in the surrounding soft tissues were observed with different types of membranes [31, 97, 100].
A total of 27 animal studies reported on the use of membranes for reconstruction of long bone defects. There were 21 studies using a small animal model (Table 4) [55, 60, 62, 76, 82, 111–126], and only six studies using a large animal model (Table 5) [127–132]. As in maxillofacial animal studies, superior bone healing has also been observed in long bones treated with a barrier-membrane compared to the non-treated defects using bioabsorbable as well as non-resorbable membranes [111, 117, 118, 121]. Bone defects treated with improved bilayer membranes displayed better regeneration of cortical bone tissue , whereas novel composite membranes displayed affluent neovascularization and bone formation with little fibrous tissue formation . The differences in chemical composition of the polylactide membranes did not seem to have an evident effect on bone healing in a small animal model , but different pore sizes resulted in differences in the intensity of the bone regeneration process . Large animal studies also showed promising results for restoration of long bone defects but only when combined with additional bone grafting material [131, 132]. When two concentric perforated membranes (the tube-in-tube implant) were used in combination with cancellous bone graft in segmental diaphyseal defects, a 'neocortex' was reconstituted with well-defined thickness .
Tables 6 and 7 summarize the clinical studies, in which absorbable membranes were used for bone regeneration of the mandible and the long bones, respectively. The absorbable membranes used were either experimental materials [57, 133], similar to the ones used in the animal studies, or commercially available material manufactured for other purposes [13, 134].
There are only three studies in humans where bioabsorbable membranes have been used for reconstruction of segmental or large mandibular bone defects using bioresorbable PLLA barrier membrane (mesh) in combination with autologous bone graft (Table 6) [33, 57, 133]. The majority of the bone defects were secondary to benign or malignant tumors of the mandible, but other causes included infection, alveolar atrophy and trauma. Overall, the preliminary clinical results were satisfactory (rated as excellent and good in 56.5% and 27.4%, respectively). Radiologically, a certain degree of bone absorption was noted in more than half of the cases; nevertheless, only in one case was the absorption significant (up to 30%).
Finally, regarding the use of bioabsorbable membranes in long bone defects, there are only two clinical studies reporting on the clinical results in a total of 16 patients (Table 7) [13, 134]. Long bone defects were mainly posttraumatic, but there were also a few cases of osteomyelitis and benign tumor resection. The bioresorbable PLLA synthetic membrane used was used in combination with autologous cancellous bone graft or bone marrow, and long bone fixation. Preliminary results showed healing of the defects and satisfactory function in all cases, except one which required further intervention.
Barrier membranes are among the most widely studied scaffolds for tissue regeneration, including bone, and the choice of type of membrane depends largely on the required duration of membrane function . Regarding bone regeneration, their use is mainly indicated for bone regeneration in sites where limited mechanical loading exists, such as in cranial, oral and maxillofacial applications. Even though there is extensive research on barrier membranes in animals, human studies are still few. Therefore, the most reliable current evidence originates mainly from studies in animals of higher phylogenetic scale which are still limited in number. Findings from the experimental setting indicate that GBR follows the same course of steps regardless of the animal. Bone quality though is highly dependent on the species (evolution hierarchy), bone healing potential (age, general nutritional status), the membrane used, local conditions (vascularity, embryological origin of bone) and load-sharing pattern of the fixation method; and, therefore, the results and the potential clinical use should be interpreted with caution [2, 13, 33, 76, 123, 130].
Long bone versus maxillofacial bone defects
According to the preliminary clinical reports, the time period for complete regeneration of bone in the mandible is three months, whereas long bones require more than two times the same period (seven months) [33, 57]. This is most likely to be attributed to the greater vascularity of the mandible and the surrounding soft tissues as well as to the different mechanical environment and less stress-shielding of the fixation method used. Furthermore, it may also be explained by the different pathways of bone formation during the regeneration process due to the different embryological origin of the mandible (intramembranous ossification) compared to long bones (endochondral ossification) . Considering these differences, the 'ideal' barrier membrane may be different for maxillofacial and orthopedic applications. For example, in the case of long bone defects, the 'ideal' membrane may require improved mechanical properties, a prolonged degradation period in the case of an absorbable membrane, and even different membrane porosity to allow vascular ingrowth from the surrounding soft tissues to optimize bone formation within the defect.
Is current evidence adequate enough for use in humans?
Despite the fact that experimental evidence is well established and preliminary results from clinical studies are encouraging, there are still several points which prevent the safe and wide use of bioabsorbable membranes in humans. Healing potential in humans is different from that of animals and it occurs with various speeds in different bones (for example, mandible versus tibia), mainly due to the difference in vascularity and/or embryological origin. Therefore, the size of the segmental defect, able to be bridged using membranes, is not yet defined in humans . Additionally, the load-bearing of different bones varies widely. Even if the bone gap may be successfully bridged by the regenerated bone, more evidence is required regarding the time it will be structurally mature to cover the functional requirements. Since load-bearing is vital for the formation and progression of bone formation, the load sharing capacity of the fixation method is of utmost importance. There is no information yet on how the new bone will develop and mature in various types of fixation methods, that is, which may be considered the optimal fixation for bone regeneration in humans.
Other major parameters affecting the efficacy of bone regeneration are the characteristics of the membranes, such as composition, thickness, porosity, and perforation size [13, 132]. These variables are yet to be defined in humans, because they may act in conjunction with the healing potential of each bone and may be used to optimize bone regeneration in bones with low healing potential or with a deficient local environment.
Specific considerations for orthopedic surgery
Bioresorbable membranes are currently being used mainly for bone regeneration in oral and maxillofacial surgery in humans. However, their use in various orthopedic conditions also represents a field of interest, especially since the number of revision surgeries [136, 137] and limb salvage procedures is increasing [138, 139]. For example, such membranes can be shaped as tubular chambers, thus preserving the continuity of the diaphysis for the repair of large diaphyseal bone defects . By forming a 'tube-in-tube implant' using two concentric perforated membranes in combination with cancellous bone-graft, the reconstitution of the 'neocortex' with well-defined thickness was possible for the treatment of segmental diaphyseal defects in sheep tibiae . Barrier membranes can also help to prevent significant absorption of the bone graft which is estimated to be up to 40% to 50% at four weeks  and seems to be due to absorption of bone that is not mechanically functioning . As these membranes are radiolucent, they allow assessment of bone formation with conventional radiographs, CT or MRI , which is important for monitoring the regeneration process.
The evidence on the efficacy for cortical perforation (decortication) during GBR procedures in an effort to enhance bone formation remains controversial . Studies have shown that cortical perforations increase the blood supply, facilitate angiogenesis, and allow access for progenitor cells from the bone marrow into the 'chamber'  whereas other studies showed that bone formation occurred from a non-injured cortical bone surface and that perforations were not required as they did not increase bone formation [59, 81]. However, since there are no relevant human clinical studies and the relevant animal studies refer to mandibular defects, where local vascularity is superior to long bones, recommendations for additional bone decortication cannot be made for orthopedic GBR applications .
Finally, barrier membranes can be used in combination with bone grafting to augment osseointegration of orthopedic implants in the case of bone defects . They may also be used for regeneration of other tissues with potential orthopedic applications, including tendon regeneration in rotator cuff repair, and post-traumatic nerve regeneration [144, 145], as the preliminary results are encouraging.
Enhancement of bone regeneration and future research
Biological augmentation of GBR with growth factors
The interest in accelerating bone formation has led researchers to combine the membrane technique with osteoinductive or growth factors. Although the concept of additional biological enhancement of bone formation using growth factors that enhance proliferation, chemotaxis, and differentiation of osteogenic cells seems promising, results are often controversial. In a study evaluating the long-term outcome of oral implants placed in bone augmented with an allograft and a collagen membrane with or without the addition of recombinant-human bone morphogenetic protein-2 (rhBMP-2), no statistically significant differences were observed regarding the clinical and radiological outcomes . On the contrary, numerous in vivo and in vitro studies have demonstrated improved bone formation when barrier membranes are loaded with platelet-derived growth factor (PDGF-BB) , basic fibroblast growth factor (FGF2) , and rhBMP-2 [99, 146, 149].
Controversial evidence may be secondary to insufficiency in maintaining therapeutic concentrations of growth factors within bone defects due to rapid clearance and use of different delivery methods with supraphysiological non-standarized doses to obtain therapeutic efficacy . Furthermore, current research usually evaluates one or a combination of two growth factors, which does not reflect the complex physiological process of bone formation. Research is ongoing to develop novel membranes and scaffolds with improved growth factor delivery systems to accelerate bone regeneration of critically-sized segmental bone defects with promising preliminary results . Moreover, with a controlled spatiotemporal delivery of growth factors, adequate local protein concentrations can be improved and maintained for optimal regenerative efficacy, avoiding the currently used supraphysiologic doses and the concomitant adverse effects . Finally, the optimal 'combination' of growth factors to be delivered has also to be established.
Other strategies to improve bone regeneration
Aiming to maximize or accelerate bone formation, supplementary strategies have been investigated in combination with barrier membranes and grafting. The potential use of low-level laser therapy (LLLT) has been evaluated as an adjunct for the regeneration of long bone defects in animal studies with positive results [114, 152]. Supplementary treatment with hyperbaric oxygen has also shown synergistic regenerative effects in the past . Additionally, preliminary results have shown that systemic administration of synthetic salmon calcitonin accelerated bone regeneration of the defects .
Research is ongoing to evaluate other methods to enhance bone regeneration, such as local administration of parathyroid hormone (PTH(1-34))  and other growth factors  with promising preliminary results. Moreover, methods to optimize surface microtopography of the membranes have also been investigated to enhance bone formation at the cellular and molecular level . Finally, in the future, improved barrier membranes can be used as part of the bone-tissue engineering approach combined with osteoprogenitor cells and/or osteopromotive factors or even gene therapy, aiming to produce improved composite grafts . Preliminary research is promising. For example, a novel three-dimensional porous polymer poly(ε-caprolactone) (PCL) scaffold coated with adeno-associated virus encoding BMP2 using both ex vivo or in vivo gene therapy, led to increased bone ingrowth with increased mechanical properties in a rat femoral defect model .
The concept of barrier membranes for restoration of large bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure and to overcome the limitations of current bone regeneration strategies. Research in this field is ongoing, with evidence being mainly gained from preclinical studies. Preliminary human studies have also shown promising results in maxillofacial, oral and orthopedic surgery. Nevertheless, before clinical applications can be recommended, future research should aim to generate and establish the 'ideal' barrier membrane. The additional use of bone-grafting materials within the membrane to fill the defect should also be evaluated, aiming to 'mimic' or even accelerate the normal process of bone formation. Finally, reproducible results and long-term observations with certified barrier membranes in animal models are required, and especially in large animal long bone defect models, as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness.
autologous bone graft
acellular dermal matrix
bovine bone marrow
bovine collagen membrane
bone morphogenetic protein
calcium alginate film
cross-linked collagen membrane
critical size defect
fibroblast growth factor
guided bone regeneration
growth differentiation factor
guided tissue regeneration
human fascia lata
human fascia temporalis
iliac crest bone graft
magnetic resonance imaging
platelet-derived growth factor
poly desaminotyrosyl-tyrosine-ethyl ester
poly L-lactide-co-glycolide-coepsilon- caprolactone
recombinant human BMP
small intestine submucosa
Dimitriou R, Jones E, McGonagle D, Giannoudis PV: Bone regeneration: current concepts and future directions. BMC Med. 2011, 9: 66-10.1186/1741-7015-9-66.
Gugala Z, Lindsey RW, Gogolewski S: New approaches in the treatment of critical-size segmental defects in long bones. Macromol Symp. 2007, 253: 147-161. 10.1002/masy.200750722.
Schmitz JP, Hollinger JO: The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res. 1986, 205: 299-308.
Aronson J: Limb-lengthening, skeletal reconstruction, and bone transport with the Ilizarov method. J Bone Joint Surg Am. 1997, 79: 1243-1258.
Bauer TW, Muschler GF: Bone graft materials. An overview of the basic science. Clin Orthop Relat Res. 2000, 371: 10-27.
Giannoudis PV, Dinopoulos H, Tsiridis E: Bone substitutes: an update. Injury. 2005, 36 (Suppl 3): S20-27.
Giannoudis PV, Einhorn TA: Bone morphogenetic proteins in musculoskeletal medicine. Injury. 2009, 40 (Suppl 3): S1-3.
Pederson WC, Person DW: Long bone reconstruction with vascularized bone grafts. Orthop Clin North Am. 2007, 38: 23-35. 10.1016/j.ocl.2006.10.006.
Masquelet AC, Begue T: The concept of induced membrane for reconstruction of long bone defects. Orthop Clin North Am. 2010, 41: 27-37. 10.1016/j.ocl.2009.07.011.
Pelissier P, Masquelet AC, Bareille R, Pelissier SM, Amedee J: Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration. J Orthop Res. 2004, 22: 73-79. 10.1016/S0736-0266(03)00165-7.
Viateau V, Guillemin G, Calando Y, Logeart D, Oudina K, Sedel L, Hannouche D, Bousson V, Petite H: Induction of a barrier membrane to facilitate reconstruction of massive segmental diaphyseal bone defects: an ovine model. Vet Surg. 2006, 35: 445-452. 10.1111/j.1532-950X.2006.00173.x.
Giannoudis PV, Faour O, Goff T, Kanakaris N, Dimitriou R: Masquelet technique for the treatment of bone defects: tips-tricks and future directions. Injury. 2011, 42: 591-598. 10.1016/j.injury.2011.03.036.
Meinig RP: Clinical use of resorbable polymeric membranes in the treatment of bone defects. Orthop Clin North Am. 2010, 41: 39-47. 10.1016/j.ocl.2009.07.012.
Retzepi M, Donos N: Guided bone regeneration: biological principle and therapeutic applications. Clin Oral Implants Res. 2010, 21: 567-576. 10.1111/j.1600-0501.2010.01922.x.
Gottlow J: Guided tissue regeneration using bioresorbable and nonresorbable devices: initial healing and long-term results. J Periodontol. 1993, 64 (11 Suppl): 1157-1165.
Hurley L, Stinchfield F, Bassett A, Lyon W: The role of soft tissues in osteogenesis. An experimental study of canine spine fusions. J Bone Joint Surg Am. 1959, 41: 1243-1254.
Boyne PJ: Regeneration of alveolar bone beneath cellulose acetate filter implants. J Dent Res. 1964, 43: 827.
Boyne PJ: Restoration of osseous defects in maxillofacial casualties. J Am Dent Assoc. 1969, 78: 767-776.
Ogiso B, Hughes FJ, Melcher AH, McCulloch CA: Fibroblasts inhibit mineralised bone nodule formation by rat bone marrow stromal cells in vitro. J Cell Physiol. 1991, 146: 442-450. 10.1002/jcp.1041460315.
Dahlin C, Linde A, Gottlow J, Nyman S: Healing of bone defects by guided tissue regeneration. Plast Reconstr Surg. 1988, 81: 672-676. 10.1097/00006534-198805000-00004.
Pitaru S, Tal H, Soldinger M, Grosskopf A, Noff M: Partial regeneration of periodontal tissues using collagen barriers. Initial observations in the canine. J Periodontol. 1988, 59: 380-386. 10.1902/jop.1922.214.171.1240.
Schenk RK, Buser D, Hardwick WR, Dahlin C: Healing pattern of bone regeneration in membrane-protected defects: a histologic study in the canine mandible. Int J Oral Maxillofac Implants. 1994, 9: 13-29.
McAllister BS, Haghighat K: Bone augmentation techniques. J Periodontol. 2007, 78: 377-396. 10.1902/jop.2007.060048.
Nyman R, Magnusson M, Sennerby L, Nyman S, Lundgren D: Membrane-guided bone regeneration. Segmental radius defects studied in the rabbit. Acta Orthop Scand. 1995, 66: 169-173. 10.3109/17453679508995515.
Scantlebury TV: 1982-1992: a decade of technology development for guided tissue regeneration. J Periodontol. 1993, 64 (11 Suppl): 1129-1137.
Aaboe M, Pinholt EM, Hjørting-Hansen E: Healing of experimentally created defects: a review. Br J Oral Maxillofac Surg. 1995, 33: 312-318. 10.1016/0266-4356(95)90045-4.
Wiltfang J, Merten HA, Peters JH: Comparative study of guided bone regeneration using absorbable and permanent barrier membranes: a histologic report. Int J Oral Maxillofac Implants. 1998, 13: 416-421.
Marouf HA, El-Guindi HM: Efficacy of high-density versus semipermeable PTFE membranes in an elderly experimental model. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000, 89: 164-170. 10.1067/moe.2000.98922.
Ostermann PA, Haase N, Rübberdt A, Wich M, Ekkernkamp A: Management of a long segmental defect at the proximal meta-diaphyseal junction of the tibia using a cylindrical titanium mesh cage. J Orthop Trauma. 2002, 16: 597-601. 10.1097/00005131-200209000-00010.
Hardwick R, Hayes BK, Flynn C: Devices for dentoalveolar regeneration: an up-to-date literature review. J Periodontol. 1995, 66: 495-505. 10.1902/jop.19126.96.36.1995.
Gielkens PF, Schortinghuis J, de Jong JR, Raghoebar GM, Stegenga B, Bos RR: Vivosorb, Bio-Gide, and Gore-Tex as barrier membranes in rat mandibular defects: an evaluation by microradiography and micro-CT. Clin Oral Implants Res. 2008, 19: 516-521. 10.1111/j.1600-0501.2007.01511.x.
Gielkens PF, Schortinghuis J, de Jong JR, Paans AM, Ruben JL, Raghoebar GM, Stegenga B, Bos RR: The influence of barrier membranes on autologous bone grafts. J Dent Res. 2008, 87: 1048-1052. 10.1177/154405910808701107.
Kinoshita Y: Regenerative medicine for jawbone. JMAJ. 2004, 47: 294-297.
Thomaidis V, Kazakos K, Lyras DN, Dimitrakopoulos I, Lazaridis N, Karakasis D, Botaitis S, Agrogiannis G: Comparative study of 5 different membranes for guided bone regeneration of rabbit mandibular defects beyond critical size. Med Sci Monit. 2008, 14: BR67-73.
Needleman IG, Worthington HV, Giedrys-Leeper E, Tucker RJ: Guided tissue regeneration for periodontal infra-bony defects. Cochrane Database Syst Rev. 2006, 2: CD001724.
Sculean A, Nikolidakis D, Schwarz F: Regeneration of periodontal tissues: combinations of barrier membranes and grafting materials - biological foundation and preclinical evidence: a systematic review. J Clin Periodontol. 2008, 35 (8 Suppl): 106-116.
Nakajima S, Fukuda T, Hasue M, Sengoku Y, Haraoka J, Uchida T: New technique for application of fibrin sealant: rubbing method devised to prevent cerebrospinal fluid leakage from dura mater sites repaired with expanded polytetrafluoroethylene surgical membranes. Neurosurgery. 2001, 49: 117-123.
Schmidmaier G, Baehr K, Mohr S, Kretschmar M, Beck S, Wildemann B: Biodegradable polylactide membranes for bone defect coverage: biocompatibility testing, radiological and histological evaluation in a sheep model. Clin Oral Implants Res. 2006, 17: 439-444. 10.1111/j.1600-0501.2005.01242.x.
Klaue K, Knothe U, Masquelet A: Effet biologique des membranes à corps etranger induites in situ sur la consolidation des greffes d'os spongieux. Rev Chir Orthop Suppl. 1995, 70: 109-110.
Patino MG, Neiders ME, Andreana S, Noble B, Cohen RE: Collagen as an implantable material in medicine and dentistry. J Oral Implantol. 2002, 28: 220-225. 10.1563/1548-1336(2002)028<0220:CAAIMI>2.3.CO;2.
Bunyaratavej P, Wang HL: Collagen membranes: a review. J Periodontol. 2001, 72: 215-229. 10.1902/jop.2001.72.2.215.
von Arx T, Broggini N, Jensen SS, Bornstein MM, Schenk RK, Buser D: Membrane durability and tissue response of different bioresorbable barrier membranes: a histologic study in the rabbit calvarium. Int J Oral Maxillofac Implants. 2005, 20: 843-853.
Alpar B, Leyhausen G, Günay H, Geurtsen W: Compatibility of resorbable and nonresorbable guided tissue regeneration membranes in cultures of primary human periodontal ligament fibroblasts and human osteoblast-like cells. Clin Oral Investig. 2000, 4: 219-225. 10.1007/s007840000079.
Behring J, Junker R, Walboomers XF, Chessnut B, Jansen JA: Toward guided tissue and bone regeneration: morphology, attachment, proliferation, and migration of cells cultured on collagen barrier membranes. A systematic review. Odontology. 2008, 96: 1-11. 10.1007/s10266-008-0087-y.
Rothamel D, Schwarz F, Sculean A, Herten M, Scherbaum W, Becker J: Biocompatibility of various collagen membranes in cultures of human PDL fibroblasts and human osteoblast-like cells. Clin Oral Implants Res. 2004, 15: 443-449. 10.1111/j.1600-0501.2004.01039.x.
Tal H, Kozlovsky A, Artzi Z, Nemcovsky CE, Moses O: Long-term bio-degradation of cross-linked and non-cross-linked collagen barriers in human guided bone regeneration. Clin Oral Implants Res. 2008, 19: 295-302. 10.1111/j.1600-0501.2007.01424.x.
Lee CK, Koo KT, Kim TI, Seol YJ, Lee YM, Rhyu IC, Ku Y, Chung CP, Park YJ, Lee JY: Biological effects of a porcine-derived collagen membrane on intrabony defects. J Periodontal Implant Sci. 2010, 40: 232-238. 10.5051/jpis.2010.40.5.232.
Coïc M, Placet V, Jacquet E, Meyer C: Mechanical properties of collagen membranes used in guided bone regeneration: a comparative study of three models. [Article in French]. Rev Stomatol Chir Maxillofac. 2010, 111: 286-290. 10.1016/j.stomax.2010.10.006.
Gupta KC, Ravi Kumar MN: Drug release behavior of beads and microgranules of chitosan. Biomaterials. 2000, 21: 1115-1119. 10.1016/S0142-9612(99)00263-X.
Klokkevold PR, Subar P, Fukayama H, Bertolami CN: Effect of chitosan on lingual hemostasis in rabbits with platelet dysfunction induced by epoprostenol. J Oral Maxillofac Surg. 1992, 50: 41-45. 10.1016/0278-2391(92)90194-5.
Shin SY, Park HN, Kim KH, Lee MH, Choi YS, Park YJ, Lee YM, Ku Y, Rhyu IC, Han SB, Lee SJ, Chung CP: Biological evaluation of chitosan nanofiber membrane for guided bone regeneration. J Periodontol. 2005, 76: 1778-1784. 10.1902/jop.2005.76.10.1778.
Lee EJ, Shin DS, Kim HE, Kim HW, Koh YH, Jang JH: Membrane of hybrid chitosan-silica xerogel for guided bone regeneration. Biomaterials. 2009, 30: 743-750. 10.1016/j.biomaterials.2008.10.025.
Kung S, Devlin H, Fu E, Ho KY, Liang SY, Hsieh YD: The osteoinductive effect of chitosan-collagen composites around pure titanium implant surfaces in rats. J Periodontal Res. 2011, 46: 126-133. 10.1111/j.1600-0765.2010.01322.x.
Asikainen AJ, Noponen J, Lindqvist C, Pelto M, Kellomäki M, Juuti H, Pihlajamäki H, Suuronen R: Tyrosine-derived polycarbonate membrane in treating mandibular bone defects. An experimental study. J R Soc Interface. 2006, 3: 629-635. 10.1098/rsif.2006.0119.
Gogolewski S, Pineda L, Büsing CM: Bone regeneration in segmental defects with resorbable polymeric membranes: IV. Does the polymer chemical composition affect the healing process?. Biomaterials. 2000, 21: 2513-2520. 10.1016/S0142-9612(00)00119-8.
Kaushiva A, Turzhitsky VM, Darmoc M, Backman V, Ameer GA: A biodegradable vascularizing membrane: a feasibility study. Acta Biomater. 2007, 3: 631-642. 10.1016/j.actbio.2007.03.003.
Kinoshita Y, Kobayashi M, Fukuoka S, Yokoya S, Ikada Y: Functional reconstruction of the jaw bones using poly(l-lactide) mesh and autogenic particulate cancellous bone and marrow. Tissue Eng. 1996, 2: 327-341. 10.1089/ten.1996.2.327.
Polimeni G, Koo KT, Pringle GA, Agelan A, Safadi FF, Wikesjo UM: Histopathological observations of a polylactic acid-based device intended for guided bone/tissue regeneration. Clin Implant Dent Relat Res. 2008, 10: 99-105. 10.1111/j.1708-8208.2007.00067.x.
Schliephake H, Kracht D: Vertical ridge augmentation using polylactic membranes in conjunction with immediate implants in periodontally compromised extraction sites: an experimental study in dogs. Int J Oral Maxillofac Implants. 1997, 12: 325-334.
Ueyama Y, Ishikawa K, Mano T, Koyama T, Nagatsuka H, Suzuki K, Ryoke K: Usefulness as guided bone regeneration membrane of the alginate membrane. Biomaterials. 2002, 23: 2027-2033. 10.1016/S0142-9612(01)00332-5.
Ueyama Y, Koyama T, Ishikawa K, Mano T, Ogawa Y, Nagatsuka H, Suzuki K: Comparison of ready-made and self-setting alginate membranes used as a barrier membrane for guided bone regeneration. J Mater Sci Mater Med. 2006, 17: 281-288. 10.1007/s10856-006-7315-1.
He H, Huang J, Chen G, Dong Y: Application of a new bioresorbable film to guided bone regeneration in tibia defect model of the rabbits. J Biomed Mater Res A. 2007, 82: 256-262.
Jianqi H, Hong H, Lieping S, Genghua G: Comparison of calcium alginate film with collagen membrane for guided bone regeneration in mandibular defects in rabbits. J Oral Maxillofac Surg. 2002, 60: 1449-1454. 10.1053/joms.2002.36108.
Kim JH, Kim MK, Park JH, Won JE, Kim TH, Kim HW: Performance of Novel Nanofibrous Biopolymer Membrane for Guided Bone Regeneration within Rat Mandibular Defect. In Vivo. 2011, 25: 589-595.
Zhang J, Huang C, Xu Q, Mo A, Li J, Zuo Y: Biological properties of a biomimetic membrane for guided tissue regeneration: a study in rat calvarial defects. Clin Oral Implants Res. 2010, 21: 392-397. 10.1111/j.1600-0501.2009.01857.x.
Humber CC, Sándor GK, Davis JM, Peel SA, Brkovic BM, Kim YD, Holmes HI, Clokie CM: Bone healing with an in situ-formed bioresorbable polyethylene glycol hydrogel membrane in rabbit calvarial defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010, 109: 372-384. 10.1016/j.tripleo.2009.10.008.
Kothiwale SV, Anuroopa P, Gajiwala AL: A clinical and radiological evaluation of DFDBA with amniotic membrane versus bovine derived xenograft with amniotic membrane in human periodontal grade II furcation defects. Cell Tissue Bank. 2009, 10: 317-326. 10.1007/s10561-009-9126-3.
Wu CA, Pettit AR, Toulson S, Grøndahl L, Mackie EJ, Cassady AI: Responses in vivo to purified poly(3-hydroxybutyrate-co-3-hydroxyvalerate) implanted in a murine tibial defect model. J Biomed Mater Res A. 2009, 91: 845-854.
Teng SH, Lee EJ, Wang P, Shin DS, Kim HE: Three-layered membranes of collagen/hydroxyapatite and chitosan for guided bone regeneration. J Biomed Mater Res B Appl Biomater. 2008, 87: 132-138.
Shabani I, Haddadi-Asl V, Soleimani M, Seyedjafari E, Babaeijandaghi F, Ahmadbeigi N: Enhanced infiltration and biomineralization of stem cells on collagen-grafted three-dimensional nanofibers. Tissue Eng Part A. 2011, 17: 1209-1218. 10.1089/ten.tea.2010.0356.
Berner A, Boerckel JD, Saifzadeh S, Steck R, Ren J, Vaquette C, Zhang JQ, Nerlich M, Guldberg RE, Hutmacher DW, Woodruff MA: Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration. Cell Tissue Res. 2012, 347: 603-612. 10.1007/s00441-011-1298-z.
Ereno C, Guimarães SA, Pasetto S, Herculano RD, Silva CP, Graeff CF, Tavano O, Baffa O, Kinoshita A: Latex use as an occlusive membrane for guided bone regeneration. J Biomed Mater Res A. 2010, 95: 932-939.
Tokuda S, Obata A, Kasuga T: Preparation of poly(lactic acid)/siloxane/calcium carbonate composite membranes with antibacterial activity. Acta Biomater. 2009, 5: 1163-1168. 10.1016/j.actbio.2008.10.005.
Zhang J, Xu Q, Huang C, Mo A, Li J, Zuo Y: Biological properties of an anti-bacterial membrane for guided bone regeneration: an experimental study in rats. Clin Oral Implants Res. 2010, 21: 321-327. 10.1111/j.1600-0501.2009.01838.x.
Chaturvedi R, Gill AS, Sikri P: Evaluation of the regenerative potential of 25% doxycycline-loaded biodegradable membrane vs biodegradable membrane alone in the treatment of human periodontal infrabony defects: a clinical and radiological study. Indian J Dent Res. 2008, 19: 116-123. 10.4103/0970-9290.40465.
Pineda LM, Busing Mc, Mienig RP, Gogolewski S: Bone regeneration with resorbable polymeric membranes. Effect of pore size on bone healing process in large defects. J Biomed Mater Res. 1996, 31: 385-394. 10.1002/(SICI)1097-4636(199607)31:3<385::AID-JBM13>3.0.CO;2-I.
Chvapil M, Holusa R, Kliment K, Stoll M: Some chemical and biological characteristics of a new collagen-polymer compound material. J Biomed Mater Res. 1969, 3: 315-332. 10.1002/jbm.820030211.
Taylor D, Smith F: Porous methyl methacrylate as an implant material. J Biomed Mater Res. 1972, 6: 467-479. 10.1002/jbm.820060112.
Klawitter J, Bagwell J, Weinstein A, Sauer B: An evaluation of bone growth into porous high density polyethylene. J Biomed Mater Res. 1976, 10: 311-323. 10.1002/jbm.820100212.
Spector M, Flemming W, Kreutner A: Bone growth into porous high-density polyethylene. J Biomed Mater Res. 1976, 10: 595-603. 10.1002/jbm.820100416.
Gutta R, Baker RA, Bartolucci AA, Louis PJ: Barrier membranes used for ridge augmentation: is there an optimal pore size?. J Oral Maxillofac Surg. 2009, 67: 1218-1225. 10.1016/j.joms.2008.11.022.
Kong L, Ao Q, Wang A, Gong K, Wang X, Lu G, Gong Y, Zhao N, Zhang X: Preparation and characterization of a multilayer biomimetic scaffold for bone tissue engineering. J Biomater Appl. 2007, 22: 223-239. 10.1177/0885328206073706.
de Santana RB, de Mattos CM, Francischone CE, Van Dyke T: Superficial topography and porosity of an absorbable barrier membrane impacts soft tissue response in guided bone regeneration. J Periodontol. 2010, 81: 926-933. 10.1902/jop.2010.090592.
Becker W, Becker B, McGuire M: Localized ridge augmentation using absorbable pins and e-PTFE barrier membranes: a new surgical technique. Case reports. Int J Periodont Restor Dent. 1994, 14: 48-61.
Jovanovic S, Nevins M: Bone formation utilizing titanium-reinforced barrier membranes. Int J Periodont Restor Dent. 1995, 15: 56-69.
Simion M, Trisi P, Piattelli A: Vertical ridge augmentation using a membrane technique associated with osseointegrated implants. Int J Periodont Restor Dent. 1994, 14: 496-511.
Ducheyne P, De Meester P, Aernoudt E: Influence of a functional dynamic loading on bone ingrowth into surface pores of orthopedic implants. J Biomed Mater Res. 1977, 11: 811-838. 10.1002/jbm.820110603.
Heck D, Nakajima I, Kelly P, Chao E: The effect of load alteration on the biological and biomechanical performance of a titanium fiber-metal segmental prosthesis. J Bone Joint Surg Am. 1986, 68: 118-126.
Pilliar R, Cameron H, Welsh R, Binnington A: Radiographic and morphologic studies of load-bearing porous-surfaced structured implants. Clin Orthop Relat Res. 1981, 156: 249-257.
Boerckel JD, Uhrig BA, Willett NJ, Huebsch N, Guldberg RE: Mechanical regulation of vascular growth and tissue regeneration in vivo. Proc Natl Acad Sci USA. 2011, 108: E674-680. 10.1073/pnas.1107019108.
Matsuo A, Chiba H, Takahashi H, Toyoda J, Abukawa H: Clinical application of a custom-made bioresorbable raw particulate hydroxyapatite/poly-L-lactide mesh tray for mandibular reconstruction. Odontology. 2010, 98: 85-88. 10.1007/s10266-009-0111-x.
Amano Y, Ota M, Sekiguchi K, Shibukawa Y, Yamada S: Evaluation of a poly-l-lactic acid membrane and membrane fixing pin for guided tissue regeneration on bone defects in dogs. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004, 97: 155-163. 10.1016/j.tripleo.2003.09.009.
Lacroix D, Prendergast PJ: A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J Biomech. 2002, 35: 1163-1171. 10.1016/S0021-9290(02)00086-6.
Stetzer K, Cooper G, Gassner R, Kapucu R, Mundell R, Mooney MP: Effects of fixation type and guided tissue regeneration on maxillary osteotomy healing in rabbits. J Oral Maxillofac Surg. 2002, 60: 427-436. 10.1053/joms.2002.31232.
Kazakos K, Lyras DN, Thomaidis V, Agrogiannis G, Botaitis S, Drosos G, Kokka A, Verettas D: Application of PRP gel alone or in combination with guided bone regeneration does not enhance bone healing process: an experimental study in rabbits. J Craniomaxillofac Surg. 2011, 39: 49-53. 10.1016/j.jcms.2010.03.005.
Hoogeveen EJ, Gielkens PF, Schortinghuis J, Ruben JL, Huysmans MC, Stegenga B: Vivosorb as a barrier membrane in rat mandibular defects. An evaluation with transversal microradiography. Int J Oral Maxillofac Surg. 2009, 38: 870-875. 10.1016/j.ijom.2009.04.002.
He H, Yan W, Chen G, Lu Z: Acceleration of de novo bone formation with a novel bioabsorbable film: a histomorphometric study in vivo. J Oral Pathol Med. 2008, 37: 378-382. 10.1111/j.1600-0714.2008.00651.x.
Zahedi S, Legrand R, Brunel G, Albert A, Dewé W, Coumans B, Bernard JP: Evaluation of a diphenylphosphorylazide-crosslinked collagen membrane for guided bone regeneration in mandibular defects in rats. J Periodontol. 1998, 69: 1238-1246. 10.1902/jop.19188.8.131.528.
Linde A, Hedner E: Recombinant bone morphogenetic protein-2 enhances bone healing, guided by osteopromotive e-PTFE membranes: an experimental study in rats. Calcif Tissue Int. 1995, 56: 549-553. 10.1007/BF00298588.
Zellin G, Gritli-Linde A, Linde A: Healing of mandibular defects with different biodegradable and non-biodegradable membranes: an experimental study in rats. Biomaterials. 1995, 16: 601-609. 10.1016/0142-9612(95)93857-A.
Dahlin C, Sandberg E, Alberius P, Linde A: Restoration of mandibular nonunion bone defects. An experimental study in rats using an osteopromotive membrane method. Int J Oral Maxillofac Surg. 1994, 23: 237-242. 10.1016/S0901-5027(05)80378-9.
Kostopoulos L, Karring T: Guided bone regeneration in mandibular defects in rats using a bioresorbable polymer. Clin Oral Implants Res. 1994, 5: 66-74. 10.1034/j.1600-0501.1994.050202.x.
Sandberg E, Dahlin C, Linde A: Bone regeneration by the osteopromotion technique using bioabsorbable membranes: an experimental study in rats. J Oral Maxillofac Surg. 1993, 51: 1106-1114. 10.1016/S0278-2391(10)80450-1.
Jégoux F, Goyenvalle E, Cognet R, Malard O, Moreau F, Daculsi G, Aguado E: Mandibular segmental defect regenerated with macroporous biphasic calcium phosphate, collagen membrane, and bone marrow graft in dogs. Arch Otolaryngol Head Neck Surg. 2010, 136: 971-978. 10.1001/archoto.2010.173.
Borges GJ, Novaes AB, Grisi MF, Palioto DB, Taba M, de Souza SL: Acellular dermal matrix as a barrier in guided bone regeneration: a clinical, radiographic and histomorphometric study in dogs. Clin Oral Implants Res. 2009, 20: 1105-1115. 10.1111/j.1600-0501.2009.01731.x.
Sverzut CE, Faria PE, Magdalena CM, Trivellato AE, Mello-Filho FV, Paccola CA, Gogolewski S, Salata LA: Reconstruction of mandibular segmental defects using the guided-bone regeneration technique with polylactide membranes and/or autogenous bone graft: a preliminary study on the influence of membrane permeability. J Oral Maxillofac Surg. 2008, 66: 647-656. 10.1016/j.joms.2007.06.664.
Bornstein MM, Bosshardt D, Buser D: Effect of two different bioabsorbable collagen membranes on guided bone regeneration: a comparative histomorphometric study in the dog mandible. J Periodontol. 2007, 78: 1943-1953. 10.1902/jop.2007.070102.
Zubery Y, Goldlust A, Antoine Alves A, Nir E: Ossification of a novel cross-linked porcine collagen barrier in guided bone regeneration in dogs. J Periodontol. 2007, 78: 112-121. 10.1902/jop.2007.060055.
Peled M, Machtei EE, Rachmiel A: Osseous reconstruction using a membrane barrier following marginal mandibulectomy: an animal pilot study. J Periodontol. 2002, 73: 1451-1456. 10.1902/jop.2002.73.12.1451.
Fritz ME, Jeffcoat MK, Reddy M, Koth D, Braswell LD, Malmquist J, Lemons J: Guided bone regeneration of large mandibular defects in a primate model. J Periodontol. 2000, 71: 1484-1491. 10.1902/jop.2000.71.9.1484.
Bernabé PF, Melo LG, Cintra LT, Gomes-Filho JE, Dezan E, Nagata MJ: Bone healing in critical-size defects treated with either bone graft, membrane, or a combination of both materials: a histological and histometric study in rat tibiae. Clin Oral Implants Res. 2012, 23: 384-388. 10.1111/j.1600-0501.2011.02166.x.
Cai YZ, Wang LL, Cai HX, Qi YY, Zou XH, Ouyang HW: Electrospun nanofibrous matrix improves the regeneration of dense cortical bone. J Biomed Mater Res A. 2010, 95: 49-57.
Lysiak-Drwal K, Dominiak M, Solski L, Zywicka B, Pielka S, Konopka T, Gerber H: Early histological evaluation of bone defect healing with and without guided bone regeneration techniques: experimental animal studies. Postepy Hig Med Dosw (Online). 2008, 62: 282-288.
Gerbi ME, Pinheiro AL, Marzola C, Limeira Júnior Fde A, Ramalho LM, Ponzi EA, Soares AO, Carvalho LC, Lima HV, Gonçalves TO: Assessment of bone repair associated with the use of organic bovine bone and membrane irradiated at 830 nm. Photomed Laser Surg. 2005, 23: 382-388. 10.1089/pho.2005.23.382.
Nasser NJ, Friedman A, Friedman M, Moor E, Mosheiff R: Guided bone regeneration in the treatment of segmental diaphyseal defects: a comparison between resorbable and non-resorbable membranes. Injury. 2005, 36: 1460-1466. 10.1016/j.injury.2005.05.015.
Moore DC, Pedrozo HA, Crisco JJ, Ehrlich MG: Preformed grafts of porcine small intestine submucosa (SIS) for bridging segmental bone defects. J Biomed Mater Res A. 2004, 69: 259-266.
Ip WY: Polylactide membranes and sponges in the treatment of segmental defects in rabbit radii. Injury. 2002, 33 (Suppl 2): 66-70.
Matsuzaka K, Shimono M, Inoue T: Characteristics of newly formed bone during guided bone regeneration: observations by immunohistochemistry and confocal laser scanning microscopy. Bull Tokyo Dent Coll. 2001, 42: 225-234. 10.2209/tdcpublication.42.225.
Nyman R, Sennerby L, Nyman S, Lundgren D: Influence of bone marrow on membrane-guided bone regeneration of segmental long-bone defects in rabbits. Scand J Plast Reconstr Surg Hand Surg. 2001, 35: 239-246. 10.1080/028443101750523140.
Caiazza S, Colangelo P, Bedini R, Formisano G, De Angelis G, Barrucci S: Evaluation of guided bone regeneration in rabbit femur using collagen membranes. Implant Dent. 2000, 9: 219-225. 10.1097/00008505-200009030-00007.
Ishikawa K, Ueyama Y, Mano T, Koyama T, Suzuki K, Matsumura T: Self-setting barrier membrane for guided tissue regeneration method: initial evaluation of alginate membrane made with sodium alginate and calcium chloride aqueous solutions. J Biomed Mater Res. 1999, 47: 111-115. 10.1002/(SICI)1097-4636(199911)47:2<111::AID-JBM1>3.0.CO;2-0.
Suckow MA, Voytik-Harbin SL, Terril LA, Badylak SF: Enhanced bone regeneration using porcine small intestinal submucosa. J Invest Surg. 1999, 12: 277-287. 10.1080/089419399272395.
Meinig RP, Buesing CM, Helm J, Gogolewski S: Regeneration of diaphyseal bone defects using resorbable poly(L/DL-lactide) and poly(D-lactide) membranes in the Yucatan pig model. J Orthop Trauma. 1997, 11: 551-558. 10.1097/00005131-199711000-00002.
Lu S, Zhang Z, Wang J: Guided bone regeneration in long bone. An experimental study. Chin Med J (Engl). 1996, 109: 551-554.
Nyman R, Magnusson M, Sennerby L, Nyman S, Lundgren D: Membrane-guided bone regeneration. Segmental radius defects studied in the rabbit. Acta Orthop Scand. 1995, 66: 169-173. 10.3109/17453679508995515.
Farso Nielsen F, Karring T, Gogolewski S: Biodegradable guide for bone regeneration. Polyurethane membranes tested in rabbit radius defects. Acta Orthop Scand. 1992, 63: 66-69. 10.3109/17453679209154853.
Rhodes NP, Hunt JA, Longinotti C, Pavesio A: In Vivo Characterization of Hyalonect, a Novel Biodegradable Surgical Mesh. J Surg Res. 2011, 168: e31-38. 10.1016/j.jss.2010.09.015.
Oh T, Rahman MM, Lim JH, Park MS, Kim DY, Yoon JH, Kim WH, Kikuchi M, Tanaka J, Koyama Y, Kweon OK: Guided bone regeneration with beta-tricalcium phosphate and poly L-lactide-co-glycolide-co-epsilon-caprolactone membrane in partial defects of canine humerus. J Vet Sci. 2006, 7: 73-77. 10.4142/jvs.2006.7.1.73.
Beniker D, McQuillan D, Livesey S, Urban RM, Turner TM, Blum B, Hughes K, Haggard WO: The use of acellular dermal matrix as a scaffold for periosteum replacement. Orthopedics. 2003, 26 (5 Suppl): s591-596.
Gerber A, Gogolewsky S: Reconstruction of large segmental defects in the sheep tibia using polylactide membranes. A clinical and radiographic report. Injury. 2002, 33 (Suppl 2): 43-57.
Gugala Z, Gogolewski S: Healing of critical-size segmental bone defects in the sheep tibiae using bioresorbable polylactide membranes. Injury. 2002, 33 (Suppl 2): 71-76.
Gugala Z, Gogolewski S: Regeneration of segmental diaphyseal defects in sheep tibiae using resorbable polymeric membranes: a pilot study. J Orthop Trauma. 1999, 13: 187-195. 10.1097/00005131-199903000-00006.
Kinoshita Y, Yokoya S, Mizutani N, Amagasa T, Kudo K, Nagayama M, Okabe S, Totsuka Y, Furuta I: Reconstruction of the mandible using bioresorbable poly[L-Lactide]mesh and autogenic particulate cancellous bone and marrow and application of dental implant. Head and Neck Cancer. 2000, 26: 525-530. 10.5981/jjhnc1974.26.525. [Abstract in English], [http://sciencelinks.jp/j-east/article/200407/000020040704A0146649.php]
Ip WY, Gogolewski S: Clinical application of resorbable polymers in guided bone regeneration. European Cells and Materials. 2004, 7 (Suppl 1): 36-[Abstract]
Berkovitz KBB: Disarticulated individual bones. Gray's Anatomy: The Anatomical Basis of Clinical Practice. Edited by: Standring S. 2005, London: Elsevier Churchill Livingstone, 463-484. 39
Pedersen AB, Johnsen SP, Overgaard S, Søballe K, Sørensen HT, Lucht U: Total hip arthroplasty in Denmark: incidence of primary operations and revisions during 1996-2002 and estimated future demands. Acta Orthop. 2005, 76: 182-189. 10.1080/00016470510030553.
Ulrich SD, Seyler TM, Bennett D, Delanois RE, Saleh KJ, Thongtrangan I, Kuskowski M, Cheng EY, Sharkey PF, Parvizi J, Stiehl JB, Mont MA: Total hip arthroplasties: what are the reasons for revision?. Int Orthop. 2008, 32: 597-604. 10.1007/s00264-007-0364-3.
Mavrogenis AF, Coll-Mesa L, Gonzalez-Gaitan M, Ucelay-Gomez R, Fabri N, Ruggieri P, Papagelopoulos PJ: Criteria and outcome of limb salvage surgery. J BUON. 2011, 16: 617-626.
Sampo M, Koivikko M, Taskinen M, Kallio P, Kivioja A, Tarkkanen M, Böhling T: Incidence, epidemiology and treatment results of osteosarcoma in Finland - a nationwide population-based study. Acta Oncol. 2011, 50: 1206-1214. 10.3109/0284186X.2011.615339.
Nicoli Aldini N, Fini M, Giavaresi G, Guzzardella GA, Giardino R: Prosthetic devices shaped as tubular chambers for the treatment of large diaphyseal defects by guided bone regeneration. Int J Artif Organs. 2005, 28: 51-57.
Jaroma HJ, Ritsilä VA: Behaviour of cancellous bone graft with and without periosteal isolation in striated muscle. An experimental study. Scand J Plast Reconstr Surg Hand Surg. 1988, 22: 47-51. 10.3109/02844318809097934.
Greenstein G, Greenstein B, Cavallaro J, Tarnow D: The role of bone decortication in enhancing the results of guided bone regeneration: a literature review. J Periodontol. 2009, 80: 175-189. 10.1902/jop.2009.080309.
Guerra I, Morais Branco F, Vasconcelos M, Afonso A, Figueiral H, Zita R: Evaluation of implant osseointegration with different regeneration techniques in the treatment of bone defects around implants: an experimental study in a rabbit model. Clin Oral Implants Res. 2011, 22: 314-322. 10.1111/j.1600-0501.2010.02002.x.
Yokoya S, Mochizuki Y, Nagata Y, Deie M, Ochi M: Tendon-bone insertion repair and regeneration using polyglycolic acid sheet in the rabbit rotator cuff injury model. Am J Sports Med. 2008, 36: 1298-1309. 10.1177/0363546508314416.
Amado S, Simões MJ, Armada da Silva PA, Luís AL, Shirosaki Y, Lopes MA, Santos JD, Fregnan F, Gambarotta G, Raimondo S, Fornaro M, Veloso AP, Varejão AS, Maurício AC, Geuna S: Use of hybrid chitosan membranes and N1E-115 cells for promoting nerve regeneration in an axonotmesis rat model. Biomaterials. 2008, 29: 4409-4419. 10.1016/j.biomaterials.2008.07.043.
Jung RE, Windisch SI, Eggenschwiler AM, Thoma DS, Weber FE, Hämmerle CH: A randomized-controlled clinical trial evaluating clinical and radiological outcomes after 3 and 5 years of dental implants placed in bone regenerated by means of GBR techniques with or without the addition of BMP-2. Clin Oral Implants Res. 2009, 20: 660-666. 10.1111/j.1600-0501.2008.01648.x.
Lee SJ, Park YJ, Park SN, Lee YM, Seol YJ, Ku Y, Chung CP: Molded porous poly (L-lactide) membranes for guided bone regeneration with enhanced effects by controlled growth factor release. J Biomed Mater Res. 2001, 55: 295-303. 10.1002/1097-4636(20010605)55:3<295::AID-JBM1017>3.0.CO;2-W.
Hong KS, Kim EC, Bang SH, Chung CH, Lee YI, Hyun JK, Lee HH, Jang JH, Kim TI, Kim HW: Bone regeneration by bioactive hybrid membrane containing FGF2 within rat calvarium. J Biomed Mater Res A. 2010, 94: 1187-1194.
Zellin G, Linde A: Importance of delivery systems for growth-stimulatory factors in combination with osteopromotive membranes. An experimental study using rhBMP-2 in rat mandibular defects. J Biomed Mater Res. 1997, 35: 181-190. 10.1002/(SICI)1097-4636(199705)35:2<181::AID-JBM6>3.0.CO;2-J.
Kolambkar YM, Dupont KM, Boerckel JD, Huebsch N, Mooney DJ, Hutmacher DW, Guldberg RE: An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. Biomaterials. 2011, 32: 65-74. 10.1016/j.biomaterials.2010.08.074.
Kolambkar YM, Boerckel JD, Dupont KM, Bajin M, Huebsch N, Mooney DJ, Hutmacher DW, Guldberg RE: Spatiotemporal delivery of bone morphogenetic protein enhances functional repair of segmental bone defects. Bone. 2011, 49: 485-492. 10.1016/j.bone.2011.05.010.
Pinheiro AL, Limeira Júnior Fde A, Gerbi ME, Ramalho LM, Marzola C, Ponzi EA, Soares AO, De Carvalho LC, Lima HC, Gonçalves TO: Effect of 830-nm laser light on the repair of bone defects grafted with inorganic bovine bone and decalcified cortical osseus membrane. J Clin Laser Med Surg. 2003, 21: 301-306. 10.1089/104454703322564523.
Dahlin C, Linde A, Röckert H: Stimulation of early bone formation by the combination of an osteopromotive membrane technique and hyperbaric oxygen. Scand J Plast Reconstr Surg Hand Surg. 1993, 27: 103-108. 10.3109/02844319309079791.
Arisawa EA, Brandão AA, Almeida JD, da Rocha RF: Calcitonin in bone-guided regeneration of mandibles in ovariectomized rats: densitometric, histologic and histomorphometric analysis. Int J Oral Maxillofac Surg. 2008, 37: 47-53. 10.1016/j.ijom.2007.07.011.
Jung RE, Cochran DL, Domken O, Seibl R, Jones AA, Buser D, Hammerle CH: The effect of matrix bound parathyroid hormone on bone regeneration. Clin Oral Implants Res. 2007, 18: 319-325. 10.1111/j.1600-0501.2007.01342.x.
Weng D, Poehling S, Pippig S, Bell M, Richter EJ, Zuhr O, Hürzeler MB: The effects of recombinant human growth/differentiation factor-5 (rhGDF-5) on bone regeneration around titanium dental implants in barrier membrane-protected defects: a pilot study in the mandible of beagle dogs. Int J Oral Maxillofac Implants. 2009, 24: 31-37.
Donos N, Retzepi M, Wall I, Hamlet S, Ivanovski S: In vivo gene expression profile of guided bone regeneration associated with a microrough titanium surface. Clin Oral Implants Res. 2011, 22: 390-398. 10.1111/j.1600-0501.2010.02105.x.
Dupont KM, Boerckel JD, Stevens HY, Diab T, Kolambkar YM, Takahata M, Schwarz EM, Guldberg RE: Synthetic scaffold coating with adeno-associated virus encoding BMP2 to promote endogenous bone repair. Cell Tissue Res. 2012, 347: 575-588. 10.1007/s00441-011-1197-3.
The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/10/81/prepub
The authors declare that they have no competing interests.
RD and GIM contributed in the preparation of this manuscript in terms of literature review and writing-up. GMC and PVG contributed in the writing of specific sections of the manuscript and in revising it critically for important intellectual content. All authors read and have given final approval of the final manuscript.
Rozalia Dimitriou, George I Mataliotakis, Giorgio Maria Calori and Peter V Giannoudis contributed equally to this work.
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Dimitriou, R., Mataliotakis, G.I., Calori, G.M. et al. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence. BMC Med 10, 81 (2012). https://doi.org/10.1186/1741-7015-10-81
- bone regeneration
- bone defect
- barrier membranes
- non-resorbable membranes
- bioresorbable/absorbable membranes