Philip H. Zeplin

Surface modification of silicone breast implants by binding the antifibrotic drug halofuginone reduces capsular fibrosis.

Background: Capsular fibrosis is one of the most severe complications that can occur in connection with silicone breast implants. Should this case arise, a periprosthetic deposition of fibroid tissue may evolve. Transforming growth factor (TGF)-&bgr; is one of the most important mediators in relation to such processes. Methods: The chinazolinone derivative halofuginone is a type I collagen synthesis inhibitor that interferes with the TGF-&bgr; signaling pathway. The work at hand examines the local antifibrotic effectiveness of halofuginone lactate, which has been biotechnologically bound to the silicone implants surface. The experiments in relation to this were conducted in vivo on two groups of seven Sprague-Dawley rats. Group I received untreated silicone implants, and group II received halofuginone-coated silicone implants. Results: Submusculary embedded halofuginone-coated silicone implants have shown no systemic side effects. The histologic and immunohistologic examinations of the periprostatic capsules revealed a significant decrease of CD68+ histiocytes, TGF-&bgr;, fibroblasts, collagen type I and type III, and capsular thickness after a 3-month period. Conclusion: The results confirmed a decrease in foreign body responses to halofuginone surface-modified silicone implants and mark their potential for obtaining a lessened capsular fibrosis by way of a local antifibrotic effect.

Phosphorylcholine-coated silicone implants: effect on inflammatory response and fibrous capsule formation.

Introduction:The formation of capsular fibrosis around silicone breast implants is a common complication in reconstructive and plastic surgery. Foreign body reaction-induced infections are quite common because of the hydrophobic surface properties of silicone and are, in addition, considered to be a causative factor of capsular fibrosis. Methods:In this experimental pilot study, 2 groups of 7 Sprague-Dawley rats were established to evaluate the periprosthetic collagen synthesis after implantation of coated silicone implants. In the first group, the textured minisilicone implants were implanted submuscularly. The second group received the biotechnologically, surface-modified phosphorylcholine (PC)-coated implants. After a 3-month period, all the rats were killed, and the capsules were examined in a histologic (hematoxylin-eosin and Masson-trichrom) and immunohistologic way (CD4, CD8, CD68, TGF-beta, fibroblasts, collagen type I, and collagen type III). Results:Significant differences were found to occur between the PC-coated and standard, textured implants with respect to the inflammatory reaction and collagen synthesis. Conclusions:The production of hydrophilic surfaces in silicone implants by way of PC-coating causes a decrease in the inflammatory reaction, and thus, a reduction of periprosthetic fibrosis. This could form the basis of a cost-effective, preventive, and therapeutic strategy with respect to the decrease in capsular fibrosis occurrence.

Reduction of burn scar formation by halofuginone-eluting silicone gel sheets: a controlled study on nude mice.

Burn scar formations can cause disfiguration and loss of dermal function. The purpose of this study was to examine whether application of modified silicone gel sheets with an antifibrotic drug halofuginone-eluting hybrid surface produce an effect on scar development. There were a total of 2 animal groups. The athymic nude mice (nu/nu) of both groups underwent transplantation of full-thickness human skin grafts onto their backs and setting of partial thickness burn injury. The status of local scar development was observed over a period of 3 months after the application of silicone gel sheets and also after application of surface-modified halofuginone-eluting silicone gel sheets. Subsequently, via real-time polymerase chain reaction, the cDNA levels from key mediators of scar formation (transforming growth factor beta, COL1A1, connective tissue growth factor, fibroblast growth factor 2, matrix metalloproteinase 2, matrix metalloproteinase 9) were established and statistically evaluated. In comparison with uncoated silicone gel sheets, the application of halofuginone-eluting silicone gel sheets lead to a significant difference in gene expression activity in scar tissue. Halofuginone-eluting hybrid surface silicone gel sheets significantly increase the antiscarring effect of adhesive silicone gel sheets by deceleration and downregulation of scar development by normalization of the expression activity.

Local inhibition of angiogenesis by halofuginone coated silicone materials

Anti-angiogenic therapy is a promising approach for the treatment of increased angiogenesis in certain diseases. We aimed to investigate the local anti-angiogenic effect of silicone implants coated with Halofuginone, an angiogenesis inhibitor that inhibits synthesis of collagen-type-I and matrix metalloproteinases. The degree of angiogenesis was observed after implantation of surface modified Halofuginone eluting silicone implants into a submuscular pocket in rats over a period of 3xa0months. Subsequently, key mediators of angiogenesis (TGF-beta-1, bFGF, COL1A1, MMP-2, MMP-9, VEGF and PDGF) were established by immunohistological staining and RT-PCR and statistically evaluated. In comparison to uncoated silicone implants, Halofuginone eluting silicone implants lead to a significant local decrease of angiogenesis. Halofuginone eluting hybrid surface silicone implants have a significant local anti-angiogenic effect by down-regulating the expression activity of key mediators of angiogenesis.

Symptomatic congenital pisiform hamate coalition.

Congenital fusions of the carpal bones are rare anomalies, which occur in less than 1% of the population. This article describes a congenital pisiform hamate coalition which became symptomatic when caused by a trauma. The condition was successfully treated with the resection of the synchondrosis, autogenous bone graft, and screw stabilization.

Verbesserung der Biokompatibilität von Silikonimplantaten durch Spinnenseidenbeschichtung: Immunhistochemische Untersuchungen zum Einfluss auf die Kapselbildung

INTRODUCTIONnOptimisation of the biocompatibility of silicone implants and reduction of capsule formation around the surface of such implants are in the focus of plastic surgical biomaterial research. In addition to its extraordinary physical and biochemical properties, spider silk shows high biocompatibility. Therefore, the coating of silicone implant surfaces with recombinant spider silk was analysed regarding foreign body reactions.nnnMATERIALS AND METHODSnIn the context of a preclinical study, miniaturised silicone implants were implanted in the back of 60 Sprague-Dawley rats. The animals were randomised; 30 animals received a texturised implant coated with the recombinant spider silk protein eADF4(C16) and 30 animals received uncoated implants. 3, 6 and 12 months after implantation, implants together with the surrounding capsules were removed and submitted to histological and immunohistochemical assessment.nnnRESULTSnCoating of silicone implants with the recombinant spider silk protein eADF4(C16) resulted in a delayed and significantly decreased foreign body reaction and a reduced capsule manifestation.nnnCONCLUSIONneADF4(C16) seems to be a promising candidate for the reduction of foreign body-associated capsule formation. Moreover, coating of other medical implants with this recombinant spider silk protein may improve their biocompatibility with little additional effort.

Comparison of various methods and materials for treatment of skin laceration by a 3-dimensional measuring technique in a pig experiment.

Background:The ability to obtain an objective comparison of scar formations by reproducible and quantitatively measurable results have posed a longstanding problem. This was especially troublesome when conclusions were to be drawn about the materials and methods applied. Two-dimensional methods (photography) gave no plastic impression about the spatial coherences in an examined scar. However, a quantifiable and reproducible recording of volumes and a 3-dimesional visualization of scars should provide the basis of any evaluation of methods and materials. Methods:The OPTOCAT 3-dimensional scanning technique that was used was provided by the Breuckmann GmbH Company (Meersburg, Germany), and it permits a 3-dimensional, contact-free recording of data. The experiment animal was the Goettinger minipig. A total of 10 animals were used to examine the process of wound healing and scar development in full skin incisions. Every animal was incised 20 times with a 10-cm long and 20 times with a 2-cm long wound. In our investigation, comparable suture materials (skin adhesive, absorbing and nonabsorbing suture materials) of the companies Braun (Histaocryl, Monosyn, Safil, Premilene) and Ethicon (Dermabond, Monocryl, Vicryl, Prolene) as well as various suture techniques were used (continuous, mattress suture, and over-and-over/interrupted suture; each once with and once without an intracutaneous suture). In the course of the trial, numerous images of all wounds—a total 1200—were taken. Thanks to the 3-dimensional software, the resulting scar volumes of lacerations, which received different wound management, were quantifiably recorded, compared, and evaluated. Results:In total, dehiscence occurred in 2.5% of all treated wounds. The greatest share (15%) fell to wounds treated with Histoacryl skin adhesive. In the end, skin adhesive, mattress, and interrupted suture all delivered similar results. An additional intracutaneous suture had, with an increasing wound length, a positive effect on the intention/wound healing, especially in connection with the application of skin adhesive. Except the combination of continuous absorbable suture and intracutaneous suture, the scar volume dwindled over time and adapted to the surrounding skin level. Continuous sutures were, by comparison, more inclined to an increased scarring (absorbable suture > nonabsorbable suture). It did not escape our notice that in case of small wounds, all various suturing materials and methods led to almost identical results. With respect to scarring, no significant difference regarding the suturing material was proven. Conclusions:If possible, the wound closure, treated with common suturing techniques and especially with skin adhesive, should be enhanced by an intracutaneous suture with an increasing length of the wound. Under certain circumstances, skin adhesive is an adequate substitute for common suturing materials and methods. The final decision about the method and material is as much closely related to the length and localization of the wound as to time exposure, efficiency, and the comfort of the patient. Summary:For objective comparison of intention and scarring, a scanning technique was used that permits a quantifiable, contact-free, single-session recording of volume differences. For this purpose, various suture materials and methods were used. Altogether, it could be shown that, if possible, wound closure treated with common suturing techniques, and especially with skin adhesive, should be enhanced by an intracutaneous suture with an increase in wound length. At the same time and under certain circumstances, skin adhesive poses an adequate substitute for the common suturing materials and methods. In the end, however, the final decision about the choice of method and material should be made depending on the localization and expanse of the wound as well as on the comfort of the patient (eg, absorbable suture/nonabsorbable suture), the time of exposure (eg, skin adhesive vs suture), and the economic efficiency (eg, producer of suture material).