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The effect of fibrin glue on fat graft survival
Journal of Plastic, Reconstructive & Aesthetic Surgery (2007) 60, 300e303
The effect of fibrin glue on fat graft survival ¨ mer Ambarciog ¨ mit C ˘lu a, ˘lu b, O Naci Karac ¸al a,*, U ¸obanog Necmettin Kutlu a a b
Department of Plastic and Reconstructive Surgery, Karadeniz Technical University, Trabzon, Turkey Department of Pathology, Karadeniz Technical University, Trabzon, Turkey
Received 21 December 2005; accepted 4 March 2006
KEYWORDS Fibrin glue; Fat graft
Summary Autologous fat transplantation for filling defects or augmenting tissue is a common procedure but may have unreliable results. While fibrin glues lead to increased proliferation of fibroblasts and local accumulation of vascular endothelial growth factor, which enhances the neovascularisation, in this study the efficacy of fibrin glues on fat graft survival was investigated. Inguinal fat pads from Spraguee Dawley rats were harvested and same volumes of autogenous fat grafts were implanted into the separate pockets with the aid of fibrin glue (Group 1) and saline solution (Group 2). All the fat grafts were harvested, washed, blotted dry, and volumetrically measured with the same method used peroperatively at 6 months after implantation. Mean graft survival values for Group 1 were compared with Group 2 and histopathological evaluation of the grafts was also made. There was a significantly higher survival rate of the grafts in Group 1 than control group (79 4% and 55 6%, respectively). Histopathological examination of the grafts demonstrated evident increase in neovascularisation of the fat grafts in the experimental group. The authors conclude that the fibrin glue significantly diminishes the fat graft resorption and further well-controlled studies are required before using fibrin glues for clinical purposes. ª 2006 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Department of Plastic and Reconstructive Surgery, Karadeniz Technical University, Kalky ´nma Mah, 61080 Trabzon, Turkey. Tel./fax: þ90 462 3775693. E-mail address: [email protected] (N. Karac ¸al).
The correction of soft-tissue volume and contour defects, especially in the facial region, represents a considerable challenge in plastic surgery. Autologous free-fat transplantation has many potential advantages over other methods of soft-tissue augmentation for small to moderate-sized defects. This tissue is abundant, easily harvested, nonimmunogenic, and has very favourable physical
1748-6815/$ - see front matter ª 2006 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2006.03.051
Effect of fibrin glue on fat graft characteristics. However, autologous fat has been grafted reluctantly in the past because of the frustrating 20e50% postgrafting resorption commonly observed.1,2 Recent attempts at improving graft survival have involved the development of alternative processing methods. Transfer of fat grafts with basic fibroblast growth factor (bFGF) bound to dextran beads has allowed for fat weight maintenance at 6 months follow-up.3 Fat grafts enriched with serum-free culture medium supplemented with anabolic nonsteroidal hormones have shown improved retention at 15 weeks.4 Not so successful has been the use of insulin to supplement fat grafts prior to transfer without any benefit to adipocyte retention in vivo.5 Fibrin glue is composed of thrombin and human fibrinogen and is an adhesive that is biodegradable. The semi-permeability of the adhesive matrix of the glue allows cellular migration and the passage of the nutrients to enrich the scarring phenomenon.6,7 Fibrin glue leads to increased proliferation of fibroblasts and local accumulation of vascular endothelial growth factor (VEGF), which enhances the neovascularisation.8 The purpose of the current study is to evaluate the effect of fibrin glue on fat graft survival.
Material and methods The study was performed in 10 SpragueeDawley rats with an average age of 8 weeks and an average weight of 325 g. All the procedures were performed in the Experimental Animals Breeding and Research Centre of the Faculty of Medicine of Karadeniz Technical University. Animal care was carried out with the approval of the Animal Experimental Ethics Committee of Karadeniz Technical University, Trabzon, Turkey. The rats were housed individually after surgery, to prevent cannibalism. Standard laboratory food for rats and water were provided ad libitum. All the rats were anaesthetized with intraperitoneal injections of sodium pentobarbital (35 mg/kg body weight). The skin of the egipastric and inguinal regions was shaved with electric clippers and then prepared with betadine (Purdue Frederick Co., Norwalk, CT, USA) and alcohol. During the surgical procedure, asepsis was maintained by providing a local sterile environment. Threecentimetre incisions were made obliquely on bilaterally inguinal region, and the skin and panniculus carnosus complex were elevated to expose the inguinal adipofascial tissue (Fig. 1). After excising the autogenous fat grafts, two pieces of fat grafts with the same volumes (0.3 cc) which were
301
Figure 1
Inguinal fat grafts were excised.
measured by liquid overflow method was obtained (volumetric measurements were made by two residents who were blinded as to group identities). These autogenous fat grafts were implanted into the separate pockets created in the loose aereolar tissue below the panniculus carnosus over the epigastric region bilaterally. After implantation of the fat grafts; the right sided pockets of all animals were filled with 0.3 cc fibrin glue (Beriplast, ZLB Behring, Malburg, Germany) homogenously (Group 1, treatment group), while the left sided pockets were instilled with the same amount of saline solution (Group 2, control group). The fibrin glue was applied with a double-syringe system and technique of leak. The pockets were closed with 5/0 monofilamentous nonabsorbable suture that served as a marker for subsequent fat graft localisation and analysis. Both skin incisions were closed with continuous 4/0 nonabsorbable sutures. All the fat grafts were harvested with the assistance of an operating microscope at 6 months after implantation. Harvested fat grafts were washed, blotted dry, and volumetrically measured with the same method used peroperatively (liquid overflow) by two residents who were blinded as to group identities. Postgrafting fat volumes were divided by preimplantation fat volumes, and graft survival percentages were derived. Mean graft survival values for Group 1 in which grafts were implanted with fibrin glue were compared with Group 2 in which the grafts were implanted with saline solution only. Harvested fat grafts were fixed in 10% buffered formalin and embedded in paraffin. Sections with a thickness of 4 mm were cut from the paraffin blocks and processed with H&E staining for histopathological examination. The slides were reviewed by a pathologist without knowledge of the method of graft implantation.
302
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Statistical analysis Statistical analysis for each group was done using Student’s test and variance analysis test was used to show differences between the groups. Statistical significance was defined as p < 0.05.
Results All of the animals tolerated the grafting procedure without complication. There was no statistically difference between groups when comparing total body weights. Successful take of the fat grafts was observed in both groups, as demonstrated by welldefined subcutaneous lumps (Fig. 2). There was no gross necrosis, liquefaction. Volume analysis of the grafts in each group (Fig. 3) showed significantly higher fat graft survival rates (mean 79 4%) in Group 1 when compared with the control group fat graft survival rates (mean 55 6%) (p < 0.01). Histopathological evaluation of the fat grafts using H&E stains revealed that well-organised, integrated fatty tissue with intact nucleus, fibrous septa, and evident increase in neovascularisation on the periphery of the grafts was prominent in Group 1 which implanted with fibrin glue when compared with the control group. Equal fine fibrous encapsulation of the grafts in both groups was observed (Fig. 4).
Discussion Free-fat autotransplantation gives somewhat unpredictable results, with its resorption rate being
Figure 2 Well-defined subcutaneous grafts at 6th month postoperatively. Mark the volumetric difference.
Figure 3 Mean fat graft survival in Group 1 was significantly higher than Group 2 (p < 0.01).
the most contentious issue to date.9 Various techniques have been suggested for improving the long-term take of these grafts, including cleansing the aspirate obtained by cannular aspiration by means of a saline wash10; centrifugation for removal of the undesired noncellular elements11; and the addition of insulin12 vitamins13 or growth factors.3 The plasmatic circulation for the initial take of a free skin graft, an analogous procedure to the grafting of fat, extends over a period of some 72 h after which the capillary circulation takes over. A similar progression of events most likely occurs in the fat graft where the diffusion of the medium into the aggregates nourishes the lipocytes until the reestablishing capillary circulation, neovascularisation, which begins at 5 days, peaked at 10 days, and remained constant thereafter only at the edge of the graft.14,15 Because nourishment depends mainly on diffusion the first 72 h, a higher ratio of surface area/volume enables a better diffusion that will increase the probability of graft take. Viability of the lipocytes is hindered by the relatively high cell density of the larger aggregates
Figure 4 Histopathological evaluation showed that a remarkable higher neovascularisation (arrows) of the grafts on Group 1 (left) compared with the control grafts (right) H&E, 100.
Effect of fibrin glue on fat graft that act to limit the tissue fluid circulation around the individual cells. Fibrin-based glues consist of naturally occurring molecules and proteins and are based on the final step in the natural coagulation pathway. Fibrinbased glues are biodegradable, usually degrade within 2 weeks, and are nontoxic to tissues. After application of fibrin glue, polymerisation occurs within seconds. Strength of adhesion increases with time and reaches a plateau up to 100 min after application.16 The fibrin-based sealants consist of two main components: [1] a fibrinogen-rich mixture, and [2] a thrombin mixture, along with Factor XIII. Thrombin catalyses the transformation of fibrinogen to fibrin, which acts as a haemostatic barrier and cell migration scaffold.7 It has been showed that thrombin and factor XIII also stimulate the proliferation of fibroblasts as growth hormones and regulate in combination with the inhibiting fibronectin the growth of fibroblasts in thrombus organisation, wound healing and in the arteriosclerotic vessel wall process.17 In an in vitro model, the effects of fibrin glue on the expression and secretion of growth factors by gastric epithelial and mesenchymal cells (fibroblasts) as well as their proliferative response and their interaction were compared with those of other matrices and it was concluded that fibrin glue leads to increased proliferation of fibroblasts and local accumulation of VEGF.8 In the present investigation, it was demonstrated that the use of fibrin glue with autogenous fat graft implantation decreases the graft resorption in volumetric analysis and the histopathological evaluation revealed that grafts implanted with the aid of fibrin glue show evident neovascularisation especially periphery of the grafts. These results may be explained with a simple mechanism: the fibrin glue used in graft implantation creates a 2-week-lasting cascade, which stabilises the graft and permits the cellular migration and the passage of nutrients to enrich the graft. As soon as fibrin glue increases the proliferation of fibroblasts and the local accumulation of VEGF and thrombin are mitogenic for some endothelial cells; the neovascularisation, which starts on 5th day postimplantation and peaks on 10th day, may occur more easily on this 2-week-lasting stabilised position. The main withdrawal of the application of biological adhesives is that the active components can cause anaphylactic reactions. It is well documented that aprotinin, a polypeptide derivative of bovine lung, has a high antigenic potential. There are two cases, one of them fatal, of deep hypotension developing after the treatment of deep hepatic lacerations with fibrin glue that contained aprotinin.18
303 We conclude that commercial fibrin sealants are beneficial for autogenous fat graft survival. Fibrin sealants may enhance the overall outcome of surgical intervention because of their adhesive and vasoactive properties, but double-blinded, controlled clinical trails are required to quantify their effects and to provide conclusive evidence of their contribution to oral and maxillofacial surgery.
References 1. Illouz YG. Present results of fat injection. Aesthetic Plast Surg 1988;12:175e81. 2. Ersek RA. Transplantation of purified autologous fat: a 3year follow-up is disappointing. Plast Reconstr Surg 1991; 87:219e27. 3. Eppley BL, Sidner RA, Platis JM, et al. Bioactivation of freefat transfers: a potential new approach to improving graft survival. Plast Reconstr Surg 1992;90:1022e30. 4. Ullmann Y, Hyams M, Ramon Y, et al. Enhancing the survival of aspirated human fat injected into nude mice. Plast Reconstr Surg 1998;101:1940e4. 5. Nguyen A, Pasyk KA, Bouvier TN, et al. Comparative study of survival of autologous adipose tissue taken and transplanted by different techniques. Plast Reconstr Surg 1990;85:378e86. 6. Saltz R, Sierra D, Feldman D, et al. Experimental and clinical applications of fibrin glue. Plast Reconstr Surg 1991;88: 1005e15. 7. Matras H. Fibrin seal: the state of the art. J Oral Maxillofac Surg 1985;43:605e11. 8. Becker JC, Domschke W, Pohle T. Biological in vitro effects of fibrin glue: fibroblast proliferation, expression and binding of growth factors. Scand J Gastroenterol 2004;39:927e32. 9. Goldwyn RM. Unproven treatment: whose benefit, whose responsibility? Plast Reconstr Surg 1988;81:946e7. 10. Niechajev I, Sevcuk O. Long-term results of fat transplantation: clinical and histologic studies. Plast Reconstr Surg 1994;94:496e506. 11. Ramon Y, Shoshani O, Peled IJ, et al. Enhancing the take of injected adipose tissue by a simple method for concentrating fat cells. Plast Reconstr Surg 2005;115:197e201. 12. Yuksel E, Weinfeld AB, Cleek R, et al. Increased free fatgraft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres. Plast Reconstr Surg 2000; 105:1712e20. 13. Ellenbogen R. Free autogenous pearl fat grafts in the face e a preliminary report of a rediscovered technique. Ann Plast Surg 1986;16:179e94. 14. Aracil Kessler JP, Diaz Torres JM, Ocana J, et al. Fat autograft: experimental study. In: Hinderer UT, editor. Plastic surgery, vol. II. Amsterdam: Elsevier; 1992. 15. Bartynski J, Marion MS, Wang TD. Histopathologic evaluation of adipose autografts in a rabbit ear model. Otolaryngol Head Neck Surg 1990;102:314e21. 16. Notowony R, Chalupka A, Nowotony C, et al. Mechanical properties of fibrinogen adhesive material. In: Winter GD, Gibbons GF, Plenk H, editors. Biomaterials. London: Wiley; 1980. 17. Bruhn HD, Pohl J. Growth regulation of fibroblasts by thrombin, factor XIII and fibronectin. Klin Wochenschr 1981;59:145e6. 18. Berguer R, Staerkel RL, Moore EE, et al. Warning: fatal reaction to the use of fibrin glue in deep hepatic wounds. Case reports. J Trauma 1991;31:408e11.
The effect of fibrin glue on fat graft survival ¨ mer Ambarciog ¨ mit C ˘lu a, ˘lu b, O Naci Karac ¸al a,*, U ¸obanog Necmettin Kutlu a a b
Department of Plastic and Reconstructive Surgery, Karadeniz Technical University, Trabzon, Turkey Department of Pathology, Karadeniz Technical University, Trabzon, Turkey
Received 21 December 2005; accepted 4 March 2006
KEYWORDS Fibrin glue; Fat graft
Summary Autologous fat transplantation for filling defects or augmenting tissue is a common procedure but may have unreliable results. While fibrin glues lead to increased proliferation of fibroblasts and local accumulation of vascular endothelial growth factor, which enhances the neovascularisation, in this study the efficacy of fibrin glues on fat graft survival was investigated. Inguinal fat pads from Spraguee Dawley rats were harvested and same volumes of autogenous fat grafts were implanted into the separate pockets with the aid of fibrin glue (Group 1) and saline solution (Group 2). All the fat grafts were harvested, washed, blotted dry, and volumetrically measured with the same method used peroperatively at 6 months after implantation. Mean graft survival values for Group 1 were compared with Group 2 and histopathological evaluation of the grafts was also made. There was a significantly higher survival rate of the grafts in Group 1 than control group (79 4% and 55 6%, respectively). Histopathological examination of the grafts demonstrated evident increase in neovascularisation of the fat grafts in the experimental group. The authors conclude that the fibrin glue significantly diminishes the fat graft resorption and further well-controlled studies are required before using fibrin glues for clinical purposes. ª 2006 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Department of Plastic and Reconstructive Surgery, Karadeniz Technical University, Kalky ´nma Mah, 61080 Trabzon, Turkey. Tel./fax: þ90 462 3775693. E-mail address: [email protected] (N. Karac ¸al).
The correction of soft-tissue volume and contour defects, especially in the facial region, represents a considerable challenge in plastic surgery. Autologous free-fat transplantation has many potential advantages over other methods of soft-tissue augmentation for small to moderate-sized defects. This tissue is abundant, easily harvested, nonimmunogenic, and has very favourable physical
1748-6815/$ - see front matter ª 2006 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2006.03.051
Effect of fibrin glue on fat graft characteristics. However, autologous fat has been grafted reluctantly in the past because of the frustrating 20e50% postgrafting resorption commonly observed.1,2 Recent attempts at improving graft survival have involved the development of alternative processing methods. Transfer of fat grafts with basic fibroblast growth factor (bFGF) bound to dextran beads has allowed for fat weight maintenance at 6 months follow-up.3 Fat grafts enriched with serum-free culture medium supplemented with anabolic nonsteroidal hormones have shown improved retention at 15 weeks.4 Not so successful has been the use of insulin to supplement fat grafts prior to transfer without any benefit to adipocyte retention in vivo.5 Fibrin glue is composed of thrombin and human fibrinogen and is an adhesive that is biodegradable. The semi-permeability of the adhesive matrix of the glue allows cellular migration and the passage of the nutrients to enrich the scarring phenomenon.6,7 Fibrin glue leads to increased proliferation of fibroblasts and local accumulation of vascular endothelial growth factor (VEGF), which enhances the neovascularisation.8 The purpose of the current study is to evaluate the effect of fibrin glue on fat graft survival.
Material and methods The study was performed in 10 SpragueeDawley rats with an average age of 8 weeks and an average weight of 325 g. All the procedures were performed in the Experimental Animals Breeding and Research Centre of the Faculty of Medicine of Karadeniz Technical University. Animal care was carried out with the approval of the Animal Experimental Ethics Committee of Karadeniz Technical University, Trabzon, Turkey. The rats were housed individually after surgery, to prevent cannibalism. Standard laboratory food for rats and water were provided ad libitum. All the rats were anaesthetized with intraperitoneal injections of sodium pentobarbital (35 mg/kg body weight). The skin of the egipastric and inguinal regions was shaved with electric clippers and then prepared with betadine (Purdue Frederick Co., Norwalk, CT, USA) and alcohol. During the surgical procedure, asepsis was maintained by providing a local sterile environment. Threecentimetre incisions were made obliquely on bilaterally inguinal region, and the skin and panniculus carnosus complex were elevated to expose the inguinal adipofascial tissue (Fig. 1). After excising the autogenous fat grafts, two pieces of fat grafts with the same volumes (0.3 cc) which were
301
Figure 1
Inguinal fat grafts were excised.
measured by liquid overflow method was obtained (volumetric measurements were made by two residents who were blinded as to group identities). These autogenous fat grafts were implanted into the separate pockets created in the loose aereolar tissue below the panniculus carnosus over the epigastric region bilaterally. After implantation of the fat grafts; the right sided pockets of all animals were filled with 0.3 cc fibrin glue (Beriplast, ZLB Behring, Malburg, Germany) homogenously (Group 1, treatment group), while the left sided pockets were instilled with the same amount of saline solution (Group 2, control group). The fibrin glue was applied with a double-syringe system and technique of leak. The pockets were closed with 5/0 monofilamentous nonabsorbable suture that served as a marker for subsequent fat graft localisation and analysis. Both skin incisions were closed with continuous 4/0 nonabsorbable sutures. All the fat grafts were harvested with the assistance of an operating microscope at 6 months after implantation. Harvested fat grafts were washed, blotted dry, and volumetrically measured with the same method used peroperatively (liquid overflow) by two residents who were blinded as to group identities. Postgrafting fat volumes were divided by preimplantation fat volumes, and graft survival percentages were derived. Mean graft survival values for Group 1 in which grafts were implanted with fibrin glue were compared with Group 2 in which the grafts were implanted with saline solution only. Harvested fat grafts were fixed in 10% buffered formalin and embedded in paraffin. Sections with a thickness of 4 mm were cut from the paraffin blocks and processed with H&E staining for histopathological examination. The slides were reviewed by a pathologist without knowledge of the method of graft implantation.
302
N. Karac ¸al et al.
Statistical analysis Statistical analysis for each group was done using Student’s test and variance analysis test was used to show differences between the groups. Statistical significance was defined as p < 0.05.
Results All of the animals tolerated the grafting procedure without complication. There was no statistically difference between groups when comparing total body weights. Successful take of the fat grafts was observed in both groups, as demonstrated by welldefined subcutaneous lumps (Fig. 2). There was no gross necrosis, liquefaction. Volume analysis of the grafts in each group (Fig. 3) showed significantly higher fat graft survival rates (mean 79 4%) in Group 1 when compared with the control group fat graft survival rates (mean 55 6%) (p < 0.01). Histopathological evaluation of the fat grafts using H&E stains revealed that well-organised, integrated fatty tissue with intact nucleus, fibrous septa, and evident increase in neovascularisation on the periphery of the grafts was prominent in Group 1 which implanted with fibrin glue when compared with the control group. Equal fine fibrous encapsulation of the grafts in both groups was observed (Fig. 4).
Discussion Free-fat autotransplantation gives somewhat unpredictable results, with its resorption rate being
Figure 2 Well-defined subcutaneous grafts at 6th month postoperatively. Mark the volumetric difference.
Figure 3 Mean fat graft survival in Group 1 was significantly higher than Group 2 (p < 0.01).
the most contentious issue to date.9 Various techniques have been suggested for improving the long-term take of these grafts, including cleansing the aspirate obtained by cannular aspiration by means of a saline wash10; centrifugation for removal of the undesired noncellular elements11; and the addition of insulin12 vitamins13 or growth factors.3 The plasmatic circulation for the initial take of a free skin graft, an analogous procedure to the grafting of fat, extends over a period of some 72 h after which the capillary circulation takes over. A similar progression of events most likely occurs in the fat graft where the diffusion of the medium into the aggregates nourishes the lipocytes until the reestablishing capillary circulation, neovascularisation, which begins at 5 days, peaked at 10 days, and remained constant thereafter only at the edge of the graft.14,15 Because nourishment depends mainly on diffusion the first 72 h, a higher ratio of surface area/volume enables a better diffusion that will increase the probability of graft take. Viability of the lipocytes is hindered by the relatively high cell density of the larger aggregates
Figure 4 Histopathological evaluation showed that a remarkable higher neovascularisation (arrows) of the grafts on Group 1 (left) compared with the control grafts (right) H&E, 100.
Effect of fibrin glue on fat graft that act to limit the tissue fluid circulation around the individual cells. Fibrin-based glues consist of naturally occurring molecules and proteins and are based on the final step in the natural coagulation pathway. Fibrinbased glues are biodegradable, usually degrade within 2 weeks, and are nontoxic to tissues. After application of fibrin glue, polymerisation occurs within seconds. Strength of adhesion increases with time and reaches a plateau up to 100 min after application.16 The fibrin-based sealants consist of two main components: [1] a fibrinogen-rich mixture, and [2] a thrombin mixture, along with Factor XIII. Thrombin catalyses the transformation of fibrinogen to fibrin, which acts as a haemostatic barrier and cell migration scaffold.7 It has been showed that thrombin and factor XIII also stimulate the proliferation of fibroblasts as growth hormones and regulate in combination with the inhibiting fibronectin the growth of fibroblasts in thrombus organisation, wound healing and in the arteriosclerotic vessel wall process.17 In an in vitro model, the effects of fibrin glue on the expression and secretion of growth factors by gastric epithelial and mesenchymal cells (fibroblasts) as well as their proliferative response and their interaction were compared with those of other matrices and it was concluded that fibrin glue leads to increased proliferation of fibroblasts and local accumulation of VEGF.8 In the present investigation, it was demonstrated that the use of fibrin glue with autogenous fat graft implantation decreases the graft resorption in volumetric analysis and the histopathological evaluation revealed that grafts implanted with the aid of fibrin glue show evident neovascularisation especially periphery of the grafts. These results may be explained with a simple mechanism: the fibrin glue used in graft implantation creates a 2-week-lasting cascade, which stabilises the graft and permits the cellular migration and the passage of nutrients to enrich the graft. As soon as fibrin glue increases the proliferation of fibroblasts and the local accumulation of VEGF and thrombin are mitogenic for some endothelial cells; the neovascularisation, which starts on 5th day postimplantation and peaks on 10th day, may occur more easily on this 2-week-lasting stabilised position. The main withdrawal of the application of biological adhesives is that the active components can cause anaphylactic reactions. It is well documented that aprotinin, a polypeptide derivative of bovine lung, has a high antigenic potential. There are two cases, one of them fatal, of deep hypotension developing after the treatment of deep hepatic lacerations with fibrin glue that contained aprotinin.18
303 We conclude that commercial fibrin sealants are beneficial for autogenous fat graft survival. Fibrin sealants may enhance the overall outcome of surgical intervention because of their adhesive and vasoactive properties, but double-blinded, controlled clinical trails are required to quantify their effects and to provide conclusive evidence of their contribution to oral and maxillofacial surgery.
References 1. Illouz YG. Present results of fat injection. Aesthetic Plast Surg 1988;12:175e81. 2. Ersek RA. Transplantation of purified autologous fat: a 3year follow-up is disappointing. Plast Reconstr Surg 1991; 87:219e27. 3. Eppley BL, Sidner RA, Platis JM, et al. Bioactivation of freefat transfers: a potential new approach to improving graft survival. Plast Reconstr Surg 1992;90:1022e30. 4. Ullmann Y, Hyams M, Ramon Y, et al. Enhancing the survival of aspirated human fat injected into nude mice. Plast Reconstr Surg 1998;101:1940e4. 5. Nguyen A, Pasyk KA, Bouvier TN, et al. Comparative study of survival of autologous adipose tissue taken and transplanted by different techniques. Plast Reconstr Surg 1990;85:378e86. 6. Saltz R, Sierra D, Feldman D, et al. Experimental and clinical applications of fibrin glue. Plast Reconstr Surg 1991;88: 1005e15. 7. Matras H. Fibrin seal: the state of the art. J Oral Maxillofac Surg 1985;43:605e11. 8. Becker JC, Domschke W, Pohle T. Biological in vitro effects of fibrin glue: fibroblast proliferation, expression and binding of growth factors. Scand J Gastroenterol 2004;39:927e32. 9. Goldwyn RM. Unproven treatment: whose benefit, whose responsibility? Plast Reconstr Surg 1988;81:946e7. 10. Niechajev I, Sevcuk O. Long-term results of fat transplantation: clinical and histologic studies. Plast Reconstr Surg 1994;94:496e506. 11. Ramon Y, Shoshani O, Peled IJ, et al. Enhancing the take of injected adipose tissue by a simple method for concentrating fat cells. Plast Reconstr Surg 2005;115:197e201. 12. Yuksel E, Weinfeld AB, Cleek R, et al. Increased free fatgraft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres. Plast Reconstr Surg 2000; 105:1712e20. 13. Ellenbogen R. Free autogenous pearl fat grafts in the face e a preliminary report of a rediscovered technique. Ann Plast Surg 1986;16:179e94. 14. Aracil Kessler JP, Diaz Torres JM, Ocana J, et al. Fat autograft: experimental study. In: Hinderer UT, editor. Plastic surgery, vol. II. Amsterdam: Elsevier; 1992. 15. Bartynski J, Marion MS, Wang TD. Histopathologic evaluation of adipose autografts in a rabbit ear model. Otolaryngol Head Neck Surg 1990;102:314e21. 16. Notowony R, Chalupka A, Nowotony C, et al. Mechanical properties of fibrinogen adhesive material. In: Winter GD, Gibbons GF, Plenk H, editors. Biomaterials. London: Wiley; 1980. 17. Bruhn HD, Pohl J. Growth regulation of fibroblasts by thrombin, factor XIII and fibronectin. Klin Wochenschr 1981;59:145e6. 18. Berguer R, Staerkel RL, Moore EE, et al. Warning: fatal reaction to the use of fibrin glue in deep hepatic wounds. Case reports. J Trauma 1991;31:408e11.