Licensee MDPI, Basel, Switzerland. This text is an open entry article distributed beneath the phrases and situations of the Inventive Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/ ).
A number of remedy modalities have been proposed to regenerate bone, together with guided bone regeneration (GBR) the place barrier membranes play an necessary function by isolating tender tissue and permitting bone to develop. Not all membranes biologically behave the identical method, as they differ from their origin and construction, with reflections on their mechanical properties and on their scientific efficiency. Collagen membranes have been broadly utilized in drugs and dentistry, due to their excessive biocompatibility and functionality of selling wound therapeutic. Lately, collagen membranes have been utilized in guided bone regeneration with comparable outcomes to non-resorbable membranes. Purpose of this work is to offer a overview on the primary options, software, outcomes, and scientific employment of the several types of collagen membranes. Comparisons with non-resorbable membranes are clarified, traits of cross-linked collagen versus native collagen, use of various grafting supplies and wish for membrane fixation are explored in an effort to acquire consciousness of the indications and limits and to have the ability to select the fitting membrane required by the scientific situation.
The goal of this paper is to check totally different commercially accessible collagen obstacles membranes and analyze their properties with the intention to make clear their scientific use.
Researchers’ curiosity relating to non-resorbable membranes and collagen membranes assorted throughout years. These days, CM are essentially the most employed and studied gadgets for bone regeneration for a number of indications, comparable to lateral bone augmentation, implant web site improvement, ridge preservation and others [ 18 , 19 , 20 ]. exhibits the variety of revealed articles by yr for non-resorbable membranes, native collagen membranes, and cross-linked collagen membranes ( ).
An “ideal” barrier membrane ought to current the next traits: biocompatibility (in an effort to forestall adversarial reactions with the encircling tissue and with the organism); tissue integration (to favor the embedding within the surrounding tissue and permitting a progressive integration of collagen fibers); dimensional stability (the positioning and form of the membrane ought to stay unaltered until degradation); dealing with (the membrane must be managed and simply positioned over the defect); selective permeability (the membrane ought to be capable of exclude undesirable epithelial cells whereas permitting osteogenic cells to proliferate); house making operate (in an effort to present house for a steady blood clot, to permit bone regeneration) [ 17 ].
Aside from resorption time, membranes meant for bone regenerative functions, ought to enable the achievement of a number of rules, revealed by Wang and Boyapati in 2006 [ 16 ] as “PASS”; main wound closure with out rigidity to allow correct therapeutic via first intention and discount of the chance of membrane publicity, angiogenesis to advertise blood provide, house upkeep to create a mattress for the undifferentiated mesenchymal cells and clot stability to permit for the right improvement of those cells.
One of the crucial fascinating points of CM is that the velocity of resorption might range. You will need to be capable of select a membrane that maintains its structural integrity for the time essential to the proliferation and maturation of the specified cells contained in the wound. Commercially accessible CM present totally different resorption time.
Presently, most resorbable membranes are manufactured from collagen and there are a selection of membranes commercially accessible ( ). CM have been proven to stimulate the fibroblast DNA synthesis, and osteoblasts present excessive ranges of adherence to CM surfaces. The in vivo biodegradation of CM takes place by endogenous collagenases into carbon dioxide and water [ 15 ].
Ideally, the biodegradation fee of the membranes ought to match the speed of latest tissue formation with no residual supplies left.
Using (CM) was launched to beat the boundaries of non-resorbable membranes. The latter are technically harder to make use of as a result of they can’t be left uncovered to the oral atmosphere and, if by accident uncovered, might result in problems. Moreover, non-resorbable membranes require a second surgical procedure to be eliminated, with a consequent higher invasiveness for the affected person [ 11 , 12 , 13 , 14 ].
The primary profitable use of resorbable membranes for GBR was reported within the early Nineties [ 8 , 9 ] and each pure and artificial polymers have been used extensively with collagen being the largely investigated [ 10 ]. These membranes are normally utilized in mixture with autogenous or artificial bone grafts, with or with out screws and pins as a result of they’re incapable of sustaining defect house due to their lack of rigidity.
Collagen kind I can also be the main element of a number of commercially accessible collagen membranes (CM) developed as an evolution of the barrier membranes firstly launched within the mid-80s [ 2 ] for regenerative functions. The precept of the so known as guided tissue regeneration was based mostly on the power of the membrane to exclude epithelial and connective cells in an effort to enhance the power of broken periodontal tissue to regenerate, with new bone, periodontal ligament and cementum formation [ 3 ]. Extra lately the membrane obstacles have been utilized to regenerate bone for the event of the implant web site (guided bone regeneration, GBR) [ 4 ]. These procedures are nonetheless broadly employed in regenerative periodontal clinics [ 5 ] and to deal with varied intraoral bone defects, not restricted to implant functions [ 6 , 7 ].
Collagen molecule alone isn’t steady. Subsequently, in nature it’s organized right into a triple helix construction, additionally known as collagen fibril. Many fibrils are then organized along with a covalent cross-linked bond to acquire a collagen fiber. There are several types of collagen, relying on the placement and performance. Thus far, greater than 20 sorts have been categorised. Collagen from kind I to kind IV are the most typical within the human physique and their localization is proven in [ 1 ].
Collagens are a household of several types of structural proteins discovered in lots of human tissues, comparable to pores and skin, blood vessels, and bone. Collagen could be synthetized by many specialised cells within the human physique, relying on the localization; fibroblasts are liable for collagen manufacturing within the connective tissue whereas osteoblasts for the bone [ 1 ]. Collagen has many options, aside from structural, together with low immunogenicity, good hemostatic capability, a chemotactic motion on regenerative cells comparable to fibroblasts and osteoblasts and, lastly, good dimensional stability.
Included papers have been pooled in 5 totally different classes of scientific curiosity: Comparability between collagen membranes and non-resorbable membranes; native collagen versus cross-linked collagen membranes; use of grafts along side collagen membranes; use of a double layer of collagen membrane; want of fixation.
Titles and abstracts of the research had been screened independently by two reviewers (LN and LS) and categorized as appropriate or not for inclusion. Full studies had been reviewed independently for research showing to satisfy the subject of curiosity or for which there was inadequate data within the title and summary to permit a transparent resolution. A hand search was additionally carried out after checking references of the recognized articles.
For this narrative overview, solely research revealed in English language had been included, and the final search was carried out in December 2019. A literature search was carried out within the PubMed/MEDLINE and ScienceDirect databases, with out limiting the years of publication and together with in vitro, in vivo and human research and critiques that reported knowledge on Collagen membranes for bone regeneration. Papers revealed earlier than December 2019 and related to the subject had been included. The next key phrases had been utilized in totally different combos: “Guided Bone Regeneration,” “GBR,” “Ridge Augmentation,” “Barrier,” “Membrane,” “Polytetrafluoroethylene,” “PTFE,” “Collagen,” “Non-Resorbable,” “Resorbable,” “Cross-Linked,” “Native Collagen,” ‘‘Graft,”
3. Outcomes and Dialogue
The digital database and the hand search recognized a complete of 987 articles. Sixty-eight articles fulfilled the inclusion standards. A few of the papers had been included in a couple of class of curiosity.
3.1. Collagen Membranes vs. Non-Resorbable Membranes A variety of membrane supplies have been utilized in experimental and scientific research to realize guided bone regeneration (GBR) together with polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), collagen, freeze-dried fascia lata, freeze-dried dura mater allografts, polyglactin 910, polylactic acid, polyglycolic acid, polyorthoester, polyurethane, polyhydroxybutyrate, calcium sulfate, micro titanium mesh [21], and titanium foils [12,21,22,23]. The primary membranes manufactured from polytetrafluoroethylene (e-PTFE; Teflon), had been proven to halt the migration of epithelial cells to the regenerating web site the place bone needed to be produced [22,24,25,26]. With the presentation of the primary profitable GBR procedures and the following large and profitable software of ePTFE membranes, this materials turned a typical for bone regeneration. Present proof helps using each non-resorbable membranes and resorbable membranes [19]. The primary drawback of non-resorbable membranes was a better fee of wound dehiscences [27,28], resulting in a excessive prevalence of infections and adversarial occasions in wound therapeutic [29,30,31], for resorbable membranes, as an alternative, limitations are a scarcity of house upkeep and a shorter degradation time. As a result of the longevity of the obstacles’ operate is a vital facet for the regenerative operate, the lack of the structural integrity of a membrane due to the macrophage- and polymorpho-nuclear leukocyte-derived enzymatic actions might turn out to be a restrict of bioresorbable gadgets [32,33]. Though the sturdiness of the barrier impact could also be diminished over the therapeutic interval, CM have a number of benefits comparable to a single-step surgical process, which decreases affected person morbidity and the chance to the newly regenerated tissues, good tissue integration, with decrease danger of membrane publicity, radiolucency that enables imaging of the regenerated bone throughout therapeutic [34]. For bioresorbable and biodegradable membranes, extra standards have to be fulfilled. Tissue reactions ensuing from the resorption of the membrane must be minimal, these reactions must be reversible, and they need to not negatively affect regeneration of the specified tissues [35]. Aside from the pointless second surgical intervention to take away the membrane, bioresorbable membranes supply some extra benefits: improved tender tissue therapeutic, the incorporation of the membranes by the host tissues (relying on materials properties), and a fast resorption in case of publicity, thus eliminating open microstructures vulnerable to bacterial contamination and self-limiting an infection [23]. Typically, for his or her organic properties, tender tissue therapeutic is improved within the presence of bioresorbable in comparison with non-resorbable membranes [27,36]. Lately, Turri et al. [37] have additionally proven that CM act as bioactive compartments relatively than passive obstacles, as they’re concerned in attracting cells into the wound space, which secrete indicators for bone regeneration and reworking, they usually promote the expression of chemotactic components, thus modulating the general osteogenic course of. Furthermore CM might adsorb mediators and progress components launched from bone and cells, a molecular course of that may improve guided bone regeneration. Zitzmann et al. [27] in contrast the resorbable collagen membrane to the traditional expanded polytetrafluoroethylene materials for guided bone regeneration in conditions involving uncovered implant surfaces. Over a 2-year interval, 25 split-mouth sufferers had been handled randomly with one of many two sorts of membranes. Adjustments in defect floor for each varieties of membranes had been statistically vital (P < 0.0001); however, no statistical significance (P > 0.94) could possibly be detected between the 2 membranes. The imply common proportion of bone fill was 92% for collagen membrane and 78% for e-PTFE membranes websites. Within the latter group, 44% wound dehiscences and/or untimely membrane elimination occurred. Writer concluded that CM had been a helpful various to the well-established expanded polytetrafluoroethylene membranes. An obstacle of CM is expounded to their unfavorable mechanical properties, which can result in collapse into the bony defect; therefore, their mixture with a bone graft is really useful when clinically utilized [38,39]. In a really current systematic overview [28] to check the proof relating to the efficacy of lateral bone augmentation procedures, essentially the most usually used kind of intervention for bone augmentation was the mixture of a xenogeneic particulate grafting materials with or with out autogenous bone particles and a resorbable collagen membrane (CM). Meta-analyses utilizing a local CM along side a xenogenic particulate grafting materials as management remedy demonstrated that the defect peak discount was not considerably totally different in comparison with the mixed knowledge of the respective check teams ( ). Vital variations, nonetheless, had been noticed in direct comparability with the second most typical membrane, a non-resorbable ePTFE membrane in favor of CM for the first final result, vertical defect decision [28]. These knowledge had been based mostly on two included research [13,40], and, since using an ePTFE membrane was thought of to be the gold customary for GBR process at implant websites with dehiscence defects [18,28], should be thought of vital. Open in a separate window The quantity of bone fill with the resorbable membrane was just like that obtained with the ePTFE membranes for some authors [27], whereas different research, in conditions the place no membrane exposures had been famous, confirmed extra favorable outcomes when it comes to bone formation utilizing the ePTFE membranes in comparison with the bioresorbable ones [41].
3.2. Native vs. Cross-Linked Collagen Pure CM are native supplies, that means that the pure collagen construction of the unique tissue and thus their pure properties are preserved in a particular manufacturing course of. Naturally grown membranes exhibit particularly good dealing with properties, comparable to pull and tear resistance, and a very good adaptation to floor contours in comparison with membranes manufactured from pressed collagen. A multi-stage cleansing course of that removes all non-collagenic proteins and antigenic parts, is used for the manufacturing. The ensuing membranes exhibit a pure three-dimensional collagen construction of collagen kind I and a decrease proportion of collagen kind III. This course of contains a number of washing steps with totally different pH options to acquire neutralization and deantigenisation. On the finish of the method a lyophilization and sterilization process is utilized [42]. Pure membranes manufactured from collagen have the main handicap of fast in vivo degradation failing to offer the structural integrity essential for your entire strategy of bone regeneration [42]. The advantages of a cross-linked collagen membrane leads to a barrier of elevated space and thickness, in contrast with the applying of a single layer collagen membrane. Cross-linked CM can cut back bone graft resorption, as membrane degradation begins shortly after implantation. It has been instructed {that a} 1-month barrier operate time for every millimeter of bone regeneration is required [43]. Garcia et al. [44] of their examine state that GBR procedures via resorbable CM obtain volumetric bone positive aspects with no statistical significance between the cross-linked and the non-cross-linked membranes. Moses et al. [45] additionally reported no substantial distinction in preserving exhausting and tender tissue quantity between cross-linked and non-cross-linked membranes. However, they carried out considerably higher if non-exposed. When it comes to biocompatibility, tissue integration and postoperative problems the outcomes of Garcia’s overview counsel that non-cross-linked membranes current higher outcomes ( ). The porous construction of non-cross-linked CM is appropriate for the formation of transmembrane blood vessels, which can additionally facilitate membrane resorption [42]. Open in a separate window Calciolari et al. [17] confirmed as native CM, derived from porcine kind I and III collagen, had been biocompatible and inert, didn’t elicit an inflammatory or international physique response, and had been capable of promote the bone regeneration course of. Membrane integrity was effectively maintained throughout the first 14 days however, at 30 days, pronounced indicators of degradation, excessive ranges of reworking and a major discount in thickness had been recognized. Related findings had been revealed by Moses et al. [45] exhibiting a major discount in membrane thickness from 14 to 30 days of therapeutic, in addition to a major discount within the complete quantity of collagen. However, at 30 days, bone formation markers (alkaline phosphatase, bone sialoprotein, osteopontin), a mesenchymal cell marker (vimentin) along with histological options instructed that bone formation was occurring incorporating fragments of the degraded collagen fibers [45,46]. To enhance the resistance to degradation and prolonging the impact of resorbable CM, bodily, chemical and enzymatic processes had been developed to enhance sturdiness by cross-linking the present collagen fibers and thus creating resorbable cross-linked CM [47,48,49]. The formation of collagen cross-links is as a result of presence of two aldehyde-containing amino acids which react with different amino acids in collagen to generate difunctional, trifunctional, and tetrafunctional cross-links. The collagen molecules assembled within the naturally occurring fibrous polymer is a prerequisite for the event of those cross-links. When that is achieved, cross-linking happens in a spontaneous, progressive trend. The chemical buildings of the cross-links dictate that very exact intermolecular alignments should happen within the collagen polymer. This appears to be a operate of every particular collagen as a result of the relative abundance of the totally different cross-links varies markedly, relying on the collagen tissue origin [50]. Numerous chemical and bodily cross-linking strategies, comparable to ultraviolet gentle, glutaraldehyde (which is a reference agent for the cross-linking reactions), glutaraldehyde plus irradiation, hexa-methylenediisocyanate (HMDIC), diphenylphosphorylazide, and enzymatic ribose cross-linking, have been used to spice up the biomechanical properties of the collagen fibers [15]. The manufacturing course of includes the extraction of collagen into monomeric fibrils, that are then reconstructed and cross-linked to kind an improved collagen-based biomaterial [51]. The in vivo degradation of collagen biomaterials could be managed by this cross-linking response. Glutaraldehyde (GA) reacts with the amino teams of the side-chains of collagen molecules, making a framework within the materials that improves the mechanical and organic stability. Some issues associated to GA cross-linking, comparable to polymerization of GA monomers in resolution resulting in heterogeneous cross-linking and cytotoxicity, have been overcome by steady response with GA at low concentrations. This methodology might produce a cloth with the identical sample of degradability utilizing smaller quantities of GA, thus avoiding cytotoxic results. Progressive remedy with low concentrations of GA is believed to induce extra homogeneous reactions within the collagen matrix [52]. The diploma of cross-linking of collagen fibers impacts the speed of degradation with extra cross-linking resulting in slower degradation and vice versa [48,53]. Rothamel et al. [54] in contrast the biodegradation of in a different way cross-linked CM to a local collagen membrane in rats. They noticed at 2, 4, 8, 16, and 24 weeks the membrane conduct with regard to vascularization, tissue integration, inflammatory response throughout resorption. Highest vascularization and tissue integration had been famous for native collagen adopted by cross-linked membranes, a few of which exhibited a international physique response throughout resorption. Moses et al. evaluated the biodegradation of three totally different commercially accessible CM. Statistically vital variations within the quantity of residual membrane materials had been recorded inside every membrane (amongst totally different time moments) and amongst totally different membranes on the identical time moments. At 28 days, the least quantity of residual collagen space was noticed within the non-cross-linked membranes (13.9% ± 10.25%), adopted by the glutaraldehyde cross-linked (24.7% ± 35.11%) and ribose cross-linked (91.3% ± 10.35%) teams. Residual membrane thickness, expressed as the proportion of baseline thickness, introduced an identical sample [45]. Cross-linked CM can cut back bone graft resorption, as membrane degradation begins shortly after implantation. It has been instructed {that a} 1-month barrier operate time for every millimeter of bone regeneration is required [43]. Chemically cross-linked CM have longer degradation instances but in addition have considerably larger membrane publicity charges, as much as 70.5% [45,55,56]. Wound dehiscence with membrane publicity has a considerable detrimental impact on GBR. Tal et al. [55] additionally demonstrated that each cross-linked and non-cross-linked membranes had been proof against tissue degradation and maintained continuity to make sure bone regeneration, nonetheless, not one of the membranes was proof against degradation when uncovered to the oral atmosphere with a considerable lack of regenerative impact. In a current human examine, comparisons of cross-linked to non-crosslinked typical collagen membrane, positioned at implant dehiscence websites confirmed that each membranes yielded comparable bone regeneration outcomes. However, it was concluded, that untimely membrane publicity of the cross-linked membrane may impair tender tissue therapeutic, or might even trigger wound infections [57].
3.3. Collagen Membranes in Conjunction with Graft As beforehand said, resorbable membranes have some limits of their mechanical properties, which can result in a low house upkeep [38,39]. CM used alone, with out particulate matter or graft blocks for GBR, normally lead to membrane compression into the defect house by overlying tender tissues [24]. For that reason, CM are additionally often mixed with block bone grafts [58,59,60,61] with or with out autogenous bone chips for graft consolidation, or xenografts or alloplastic bone substitutes [62,63]. Autogenous bone grafts present some favorable traits for bone regeneration [64], for instance osteoconductivity [4], osteogenicity [65], and osteoinductivity [66], however their harvesting might enhance affected person morbidity as a result of extra surgical procedures [67] and it’s reported a quick degradation, with the lack of the house making operate. So as to overcome this drawback and to acquire a slower degradation fee, bone substitute supplies have been extensively evaluated [68]. Benic et al. [69] confirmed {that a} block bone substitute together with a collagen membrane and fixation pins was superior to a particulate bone substitute with a collagen membrane and fixation pins with respect to the thickness and to the vertical acquire of the augmented exhausting tissue after 6 months of therapeutic compared to the websites grafted with a particulate deproteinized bovine bone mineral (DBBM). Whereas bone blocks are extra indicated to acquire vertical bone will increase, resorbable membranes together with particulated bovine bone can be utilized for the augmentation of horizontally poor ridges [70]. Bone substitutes could be blended with particulated autogenous bone so as to add extra osteogenic components [71,72]. Meloni et al. [20] confirmed that sufferers, having lower than 4 mm of residual horizontal bone width had been chosen and consecutively handled with resorbable CM and a 1:1 combination of particulated anorganic bovine bone and autogenous bone, 7 months earlier than implant placement. A mean horizontal bone acquire of 5.03 ± 2.15 mm (95% CI: 4.13–5.92 mm) was obtained. CM and totally different grafting supplies could be adopted additionally to carry out ridge preservation methods. Though a discount of alveolar ridge resorption could be achieved with the applying of resorbable CM with out bone grafts, Iasella et al. [73] confirmed that extraction websites with bioresorbable membrane confirmed much less vertical and horizontal bone loss and higher bone fill. A current preclinical examine assessed the in vivo efficiency of a collagen-containing equine block, of a deproteinized bovine bone mineral (DBBM) block and of particulate DBBM used for GBR with simultaneous implant placement [74]. GBR with bone substitute blocks result in larger ridge dimensions than empty controls. The equine block with collagen membrane obtained essentially the most favorable outcomes in exhausting and tender tissue contours adopted by deproteinized bovine bone mineral block and particulated deproteinized bovine bone mineral with collagen membrane.
3.4. Single Layer vs. Double Layer CM can be utilized as a single layer or with a double layer, by overlapping two membranes. Buser et al. [75,76] for the primary time proposed using a double layer for guided bone regeneration. The rationale for using a double membrane layer is the discount of micro-movements and the perfect stabilization of the graft, optimizing the sheltering within the space to be regenerated. Kim et al. [77] verified the advance in bone block stability for exhausting tissue regeneration utilizing the only or double layer on a rabbit mannequin. They reported a statistically vital larger bone quantity after 4 months between the double layer and the only layer teams, however no statistically vital distinction at 6 months between the 2 teams. In 2017, Choi et al. [78] carried out a human examine to check the alveolar ridge preservation utilizing single- or double-layer collagen membrane. The 2 teams confirmed no distinction when it comes to preservation of horizontal and vertical dimensions of the alveolar socket. Kozlovski et al. [46] investigated whether or not there was a distinction between a single and a double membrane layer within the restore of bone defects in a rat mannequin. The examine confirmed a statistically vital distinction within the collagen space (0.09 ± 0.05 mm2 vs. 0.047 ± 0.034 mm2 respectively within the double and single layer.) On the opposite aspect, no statistically vital distinction was seen within the discount of thickness between 4 and 9 weeks. Some authors have reported higher outcomes of bone formation when utilizing a local collagen membrane in a double-layer method as an alternative of utilizing it in a single layer in GBR of horizontal ridges [76]. Von Arx and Buser [76] in 2006 performed a examine just like Antoun et al. [79] by masking horizontally grafted websites by bone blocks and bovine bone particles and coated by a double membrane native collagen membrane. This system allowed, in accordance with the authors, a greater safety of the graft and elevated the soundness of the membrane. Furthermore, this double collagen barrier offered a rise within the survival of the membrane and a protracted safety of the horizontally grafted ridge by a bone block. Outcomes confirmed a discount of solely 7% of the full width of the graft after 6 months. Different research tried to research the consequences of single- and double-layered CM on the bone resorption and augmentation efficacy of onlay block bone grafts. The outcomes indicated that the double-layer method was related to a decreased collapse tendency and a better bone density of onlay bone graft than the single-layer membrane method, defined by the protecting results of graft resorption throughout the therapeutic time [75,76,77]. Double-layered membranes are thought to retain their barrier operate for an extended time period. Nevertheless, in a special examine, designed to judge histologically and histomorphometrically the bone regeneration in vital dimension calvarial defects in rats grafted with both a deproteinized bovine bone mineral alone or together with a single or double layer of native bilayer collagen membrane, a single-layer collagen membrane was adequate to permit the exclusion of connective tissue cells or cells from muscular origin, and including a second membrane layer didn’t exhibit an extra enhance within the quantity of latest bone formation in comparison with a single-layer collagen membrane. The writer commented that though a scarcity of great enchancment in efficacy, this double cowl had an undoubtful benefit within the stabilization of the graft [80].