Peter E. M. Butler

Tissue engineered neocartilage using plasma derived polymer substrates and chondrocytes

&NA; This study demonstrates that fibrin monomers can be polymerized into moldable gels and used for the encapsulation of isolated chondrocytes. This biologically derived scaffold will maintain three‐dimensional spatial support, allowing new tissue development in a subcutaneous space. Chondrocytes isolated from the glenohumeral and humeroradioulnar joints of a calf were combined with cyroprecipitate and polymerized with bovine thrombin to create a fibrin glue gel with a final cell density of 12.5 × 106 cells/ml. The polymer‐chondrocyte constructs were implanted subcutaneously in 12 nude mice and incubated for 6 and 12 weeks in vivo. Histologic and biochemical analysis including deoxyribonucleic acid (DNA) and glycosaminoglycan quantitation confirmed the presence of actively proliferating chondrocytes with production of a well‐formed cartilaginous matrix in the transplanted samples. Control specimens from 12 implantation sites consisting of chondrocytes alone or fibrin glue substrates did not demonstrate any gross or histologic evidence of neocartilage formation. Moldable autogenous fibrin glue polymer systems have a potential to serve as alternatives to current proprietary polymer systems used for tissue engineering cartilage as well as autogenous grafts and alloplastic materials used for facial skeletal and soft‐tissue augmentation. (Plast. Reconstr. Surg. 101: 1580, 1998.)

Biomaterials and scaffold design: key to tissue-engineering cartilage.

Cartilage remains one of the most challenging tissues to reconstruct or replace, owing to its complex geometry in facial structures and mechanical strength at articular surfaces in joints. This non‐vascular tissue has poor replicative capacity and damage results in its functionally inferior repair tissue, fibrocartilage. This has led to a drive for advancements in tissue engineering. The variety of polymers and fabrication techniques available continues to expand. Pore size, porosity, biocompatibility, shape specificity, integration with native tissue, degradation tailored to rate of neocartilage formation and cost efficiency are important factors which need consideration in the development of a scaffold. The present review considers the current polymers and fabrication methodologies used in scaffold engineering for cartilage and postulates whether we are closer to developing the ideal scaffold for clinical application.

Hyperhidrosis: A review of current management

Primary hyperhidrosis is a troublesome disorder of excessive perspiration that affects as much as 1 percent of the population. Sufferers are usually young and are often affected by related social, professional, and psychological problems. Many methods for treating hyperhidrosis exist; however, no single treatment is without its weakness or complications. This article aims to clarify the issues related to the use of each treatment modality, including the most recently proposed method using botulinum toxin.

Injectable cartilage using polyethylene oxide polymer substrates.

&NA; This Study demonstrates that polyethylene oxide gels, which are biocompatible and biodegradable synthetic polymers, can be utilized for the encapsulation of isolated chondrocytes and maintenance of three‐dimensional spatial support for new tissue development. Chondrocytes isolated from the glenohumeral and humeroradioulnar joints of a calf were added to a 20% polyethylene oxide solution in H‐ams F‐12 medium to generate a final cellular density of 10 × 106/ml. The polymer‐chondrocyte constructs were injected through a 22‐gauge needle in 500‐μl aliquots subcutaneously in 12 nude mice and incubated for 6 and 12 weeks in vivo. Histologic and biochemical analyses including deoxyribonucleic acid and glycosaminoglycan quantitative analyses confirmed the presence of actively proliferating chondrocytes with production of a well‐formed cartilaginous matrix in the transplanted samples. Control specimens from eight implantation sites consisting of chondrocytes alone or polyethylene oxide substrates did not demonstrate any gross or histologic evidence of neocartilage formation. These findings demonstrate the potential use of an injectable and moldable polymer substrate that can support cell proliferation and matrix synthesis after subcutaneous transplantation for neocartilage generation. The use of functional biologic tissue substitutes may serve as an alternative solution to current methods of augmentation or reconstruction of structural craniofacial contour deformities. (Plast. Reconstr. Surg. 98: 843, 1996.)

Silsesquioxane nanocomposites as tissue implants.

Background: Silicone implants are being used increasingly worldwide, especially in breast augmentation procedures. The most common morbidity observed is capsular contracture, which occurs in 15 percent of cases. To overcome this problem, the authors have developed a novel nanocomposite based on polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU) for use as tissue implants. Methods: These polymers were implanted in six healthy sheep (n = 6) for 36 months and a siloxane served as the positive control. After explantation, these polymers were extracted, as was the surrounding capsule, if any. Attenuated total reflectance Fourier transform infrared spectroscopy analysis was performed to look for signs of surface degradation on the polymers and histopathologic and electron microscopic examinations were performed to study the interaction between the biomaterial and the host environment in greater detail. Results: After implantation, the authors observed minimal inflammation of the nanocomposite within the sheep model as compared with the siloxane control. Contact angle measurements and fibrinogen enzyme-linked immunosorbent assay tests were then conducted on the POSS-PCU nanocomposite to determine the reason for this behavior. The increased fibrinogen adsorption on POSS-PCU, its amphilicity, and large contact-angle hysteresis indicated that POSS-PCU inhibits inflammation by adsorbing and inactivating fibrinogen on its surface. In complete contrast, the control siloxane in the same setting demonstrated very significant inflammation and degradation, resulting in capsular formation. Naturally, there was no evidence of degradation of the nanocomposite compared with the siloxane control. Conclusions: POSS-PCU nanocomposites have enhanced interfacial biocompatibility and better biological stability as compared with conventional silicone biomaterials, thus making them safer as tissue implants.

Achievements and challenges in composite tissue allotransplantation.

Overall, more than 60 hand/forearm/arm transplantations and 16 face transplantations have been performed in the past 12 years. In the European experience summarized here, three grafts have been lost in response to a vascular thrombosis (n = 1), rejection and incompliance with immunosuppression (n = 1) and death (n = 1). The overall functional and esthetic outcome is very satisfactory, but serious side effects and complications related to immunosuppression are challenges hindering progress in this field. The high levels of immunosuppression, skin rejection, nerve regeneration, donor legislation and the acceptance level need to be addressed to promote growth of this promising new field in transplantation and reconstructive surgery.

The endothelialization of polyhedral oligomeric silsesquioxane nanocomposites - An in vitro study

It has been recognized that seeding vascular bypass grafts with endothelial cells is the ideal method of improving their long-term patency rates. The aim of this study was to assess the in vitro cytocompatibility of a novel silica nanocomposite, polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU) and hence elicit its feasibility at the vascular interface for potential use in cardiovascular devices such as vascular grafts. Using primary human umbilical vein endothelial cells (HUVEC), cell viability and adhesion were studied using AlamarBlue assays, whereas cell proliferation on the polymer was assessed using the PicoGreen dye assay. Cellular confluence and morphology on the nanocomposite were analyzed using light and electron microscopy, respectively. Our results showed that there was no significant difference between cell viability in standard culture media and POSS-PCU. Endothelial cells were capable of adhering to the polymer within 30 min of contact (Students t-test, p<0.05) with no difference between POSS-PCU and control cell culture plates. POSS-PCU was also capable of sustaining good cell proliferation for up to 14d even from low seeding densities (1.0×103 cells/cm2) and reaching saturation by 21 d. Microscopic analysis showed evidence of optimal endothelial cell adsorption morphology with the absence of impaired motility and morphogenesis. In conclusion, these results support the application of POSS-PCU as a suitable biomaterial scaffold in bio-hybrid vascular prostheses and biomedical devices.

Vascular delay revisited.

Summary: The technique of vascular delay has been used by plastic surgeons for nearly 500 years and has proven useful for reliably transferring tissue and allowing for a greater volume of tissue to be reliably harvested. Delay procedures are an essential plastic surgical tool for a variety of aesthetic and reconstructive procedures. Despite the widespread use of vascular delay procedures, the mechanism by which this phenomenon occurs remains unclear. A number of groups have exhaustively examined microvascular changes that occur during vascular delay. Theories have been proposed ranging from the dilation of choke vessels to changes in metabolism and new blood vessel formation. Inherent in these theories is the concept that ischemia is able to act as the primary stimulus for vascular changes. The purpose of this review is to revisit the theories proposed to underlie the delay phenomenon in light of recent advances in vascular biology. In particular, the participation of bone marrow–derived endothelial progenitor cells in the delay phenomenon is explored. Greater understanding of the role these cells play in new blood vessel formation will be of considerable clinical benefit to high-risk patients in future applications of delay procedures.

Craniofacial skeletal fixation using biodegradable plates and cyanoacrylate glue.

&NA; This study examined the feasibility of fixation of craniofacial bone using Lactosorb biodegradable plates adhered to bone with butyl‐2‐cyanoacrylate adhesive (Histoacryl) in a pig. The stability and bone‐healing characteristics of this rigid fixation method were studied and compared with standard rigid fixation using metal plates and screws on osteotomy sites in the frontal bones and infraorbital rims. Rectangular osteotomies (2.0 × 3.0 cm) were performed on the right and left sides of the frontal bone and wedge‐shaped osteotomies (1.5 × 1.7 cm) were made on the left and right infraorbital rims in seven Yorkshire pigs. Metal plates were applied with screws to the osteotomies on one side, and the other side was fixed with a biodegradable plate and butyl‐2‐cyanoacrylate. The animals were sacrificed at 8 weeks, and both sides were compared biomechanically and histologically. Radiographic, biomechanical, and histologic analyses were performed to evaluate skeletal stability, contour, accurate positioning of bony fragments, bone healing, and maximum torque to failure of the repair sites. Clinical and radiographic observations demonstrated stability of the bone fragments without any evidence of displacement. According to Students t test for paired data, no statistical difference was found in the maximum torque to failure of fragments fixed with biodegradable plates and glue compared with those fixed with metal plates and screws (p > 0.05), whether or not a gap existed at the osteosynthesis site. Although the sample size was small, no differences were noted between the two types of treatment groups. This study demonstrates that rigid internal fixation of osteotomized cranial bone fragments using biodegradable plates and butyl‐2‐cyanoacrylate is as effective as metal plate and screw fixation in this animal model.

Training in microsurgical skills : Does course-based learning deliver?

Practical skill training courses are an increasingly popular method of teaching surgical skills. Few data are available from instructional courses indicating how successful they are at imparting practical skills to those individuals who attend them. We aimed to identify the skill benefits gained by trainee surgeons attending a 5‐day microsurgical skills course. A global scoring system was devised to objectively assess the level of skill employed by trainees to complete an arterial microvascular anastamosis. Vessel patency, anastamotic construct, and care of tissue in the surrounding operative field were taken into account. Postoperative tissue viability and physiological vessel function following anastamosis were also investigated. The majority of surgeons (60% ) exhibited an increase in their level of microsurgical skill during the course. The remaining candidates remained static or deteriorated. Attendance at this microsurgical training workshop resulted in an improvement in microsurgical skills in most trainees. In‐course assessment by training courses would allow identification of individuals requiring further training or skill refinement.