Grafts in myringoplasty : utilizing a silk fibroin scaffold as a novel device

Chronic perforations of the eardrum or tympanic membrane represent a significant source of morbidity worldwide. Myringoplasty is the operative repair of a perforated tympanic membrane and is a procedure commonly performed by otolaryngologists. Its purpose is to close the tympanic membrane, improve hearing and limit patient susceptibility to middle ear infections. The success rates of the different surgical techniques used to perform a myringoplasty, and the optimal graft materials to achieve complete closure and restore hearing, vary significantly in the literature. A number of autologous tissues, homografts and synthetic materials are described as graft options. With the advent and development of tissue engineering in the last decade, a number of biomaterials have been studied and attempts have been made to mimic biological functions with these materials. Fibroin, a core structural protein in silk from silkworms, has been widely studied with biomedical applications in mind. Several cell types, including keratinocytes, have grown on silk biomaterials, and scaffolds manufactured from silk have successfully been used in wound healing and for tissue engineering purposes. This review focuses on the current available grafts for myringoplasty and their limitations, and examines the biomechanical properties of silk, assessing the potential benefits of a silk fibroin scaffold as a novel device for use as a graft in myringoplasty surgery.

Localisation and William Macewen`s early brain surgery part I: the controversy

Neurosurgery for the removal of brain tumours based on localising signs is usually dated from the 1884 operation by Bennett and Godlee. However, within weeks of that operation claims were made on behalf of William Macewen, the Glasgow surgeon, to have been the real pioneer of such surgery. According to Macewen's protagonists, he had conducted seven similar operations earlier than Bennett and Godlee and, in a notable 1888 address, Macewen described these seven pre-1884 cases and a number of others operated on after 1884. This paper, which is in two parts, contains an evaluation of the claims made for the priority of Macewen's pre-1884 operations. Part I deals mainly with Macewen's work in fields other than brain surgery that are relevant to it and sets out the facts of the controversy. It begins with a brief biography of Macewen, describes his pioneering work in antiseptic and aseptic surgery, his work on osteotomy and bone regeneration, and his use in brain surgery of the knowledge so gained. Part I concludes with an examination of the battle waged in the newspapers between Macewen's and Bennett's and Godlee's supporters, and of previously unpublished correspondence between Macewen himself, David Ferrier and Hughes Bennett. The primary records of the patients on whom Macewen operated, together with other materials relevant to the controversy, are examined in Part II.

Small diameter Polyurethane vascular graft reinforced by elastic weft-knitted tubular fabric of polyester / spandex

Small diameter vascular grafts were fabricated from pure Polyurethane (PU) as well as PU reinforced with a tubular weft-knitted fabric. The tensile properties of the reinforced composite vascular grafts were compared with that of the tubular fabric itself and the pure PU vascular grafts. The elasticity and strength of the reinforced vascular grafts were improved compared with the tubular fabric. Strength of the reinforced vascular grafts was 5–10 times of the strength of the pure PU vascular grafts. Expanding the tubular fabric to increase the inner diameter of the reinforced vascular graft reduced the graft’s strength and initial modulus, but the difference was reduced as the PU content was increased. For grafts of the same inner diameter, increasing the PU content increased the thickness and strength of the graft wall, which led to a general increase in the strength and initial modulus of the composite vascular grafts.

Endothelialisation and cell retention on gelation-chitosan coated electrospun polyurethane, poly (lactide-co-glycolide) and collagen-coated pericardium

Arterial bypass and heart valve replacements are two of the most common surgical treatments in cardiovascular surgery today. Currently, artificial materials are used as substitute for these cardiac tissues. However, these foreign materials do not have the ability to grow, repair or remodel and are thrombogenic, leading to stenosis. With the aid of tissue engineering, it is possible to develop functional identical copies of healthy heart valves and arteries, which are biocompatible. Although much effort has been made into this area, there are still inconsistencies with respect to
endothelialisation and cell retention on synthetic biological grafts. These variations may be attributed to differences in factors such as cell seeding density, incubation periods and effects of shear stress. In this study, we have compared the endothelialisation and cell retention between gelain chitosan-coated electrospun polyurethane (PU), poly (lactide co-glycolide) (PGA/PLA) and collagen-coated pericardium. Endothelial cells adhered to all of the materials as early as 1–day post seeding. After 7-day of seeding, the coverage on PU was almost 45% and that on PGA/PLA was about 25% and the least was on collagen-coated pericardium of approximately 15%. It was observed that the PU showed superior cell coverage and cell retention in comparison to the PGA/PLA and collagen-coated pericardium.

Polyethyleneterephthalate provides superior retention of endothelial cells during shear stress compared to polytetrafluoroethylene and pericardium

Background

Polyethyleneterephthalate (PET) and polytetrafluoroethylene (PTFE) are polymers successfully used as large diameter arterial grafts for peripheral vascular surgery. However, these prosthetic grafts are rarely used for coronary bypass surgery because of their low patency rates. Endothelialisation of the lumenal surface of these materials may improve their patency. This study aimed to compare the endothelialisation of PET, PTFE and pericardium by examining their seeding efficiency over time and the effect of various shear stresses on retention of endothelial cells.

Methods


Ovine endothelial cells at 4 × 105 cells/cm2 were seeded onto PET, PTFE and pericardium, and cultured for 1–168 hours. Cell coverage was determined via en face immunocytochemistry and cell retention was quantified after being subjected to shear stresses ranging from 0.018 to 0.037 N/m2 for 15, 30 and 60 minutes.

Results

Endothelial cells adhered to all of the materials one hour post-seeding. PET exhibited better cell retention rate, ranging from 66.9 ± 5.6% at 0.018 N/m2 for 15 min to 44.7 ± 1.9% at 0.037 N/m2 for 60 minutes, when compared to PTFE and pericardium (p < 0.0001, three-way ANOVA).

Conclusion

PET shows superior retention of endothelial cells during shear stress compare to PTFE and pericardium.

Preliminary results of the application of a silk fibroin scaffold to otology

The surgical treatment to repair chronic tympanic membrane perforations is myringoplasty. Although multiple autologous grafts, allografts, and synthetic graft materials have been used over the years, no single graft material is superior for repairing all perforation types. Recently, the remarkable properties of silk fibroin protein have been studied, with biomedical and tissue engineering applications in mind, across a number of medical and surgical disciplines. The present study examines the use of silk fibroin for its potential suitability as an alternative graft in myringoplasty surgery by investigating the growth and proliferation of human tympanic membrane keratinocytes on a silk fibroin scaffold in vitro. Light microscopy, immunofluorescent staining, and confocal imaging all reveal promising preliminary results. The biocompatibility, transparency, stability, high tensile strength, and biodegradability of fibroin make this biomaterial an attractive option to study for this utility.

3D fibrous structures as cardiovascular implants

Medical textiles are a highly specialised stream of technical textiles industry with a growing range of applications. A significant advancement has been achieved in surgical products or biomedical textiles (implantable/non-implantable) with the advent of 3D textile manufacturing techniques. Cardiovascular soft tissue implants (vascular grafts) have been a field of interest over decades for use of innovative 3D tubular structures in treatment of cardiovascular diseases. In the field of soft tissue implants, knitted and woven tubular structures are being used for large diameter blood vessel replacements. Advent of electrospinning and tissue engineering techniques has been able to provide promising answers to small diameter vascular grafts. The aim of this review is to outline the approaches in vascular graft development utilising different 3D tubular structure forming techniques. The emphasis is on vascular graft development techniques that can help improve treatment efficacy in future.

Amyloid formation results in recurrence of hyperglycaemia following transplantation of human IAPP transgenic mouse islets

Aims/hypothesis Islet transplantation is a potential cure for diabetes; however, rates of graft failure remain high. The aim of the present study was to determine whether amyloid deposition is associated with reduced beta cell volume in islet grafts and the recurrence of hyperglycaemia following islet transplantation.

Methods We transplanted a streptozotocin-induced mouse model of diabetes with 100 islets from human IAPP (which encodes islet amyloid polypeptide) transgenic mice that have the propensity to form islet amyloid (n = 8–12) or from non-transgenic mice that do not develop amyloid (n = 6–10) in sets of studies that lasted 1 or 6 weeks.

Results Plasma glucose levels before and for 1 week after transplantation were similar in mice that received transgenic or non-transgenic islets, and at that time amyloid was detected in all transgenic grafts and, as expected, in none of the non-transgenic grafts. However, over the 6 weeks following transplantation, plasma glucose levels increased in transgenic but remained stable in non-transgenic islet graft recipients (p < 0.05). At 6 weeks, amyloid was present in 92% of the transgenic grafts and in none of the non-transgenic grafts. Beta cell volume was reduced by 30% (p < 0.05), beta cell apoptosis was twofold higher (p < 0.05), and beta cell replication was reduced by 50% (p < 0.001) in transgenic vs non-transgenic grafts. In summary, amyloid deposition in islet grafts occurs prior to the recurrence of hyperglycaemia and its accumulation over time is associated with beta cell loss.

Conclusions/interpretation Islet amyloid formation may explain, in part, the non-immune loss of beta cells and recurrence of hyperglycaemia following clinical islet transplantation.

Optimization of bypass graft using FSI numerical method

It is well documented in literature that the coronary artery bypass graft is normally fail after a short period of time, due to the development of plaque known as intimal hyperplasia within the graft. Various in vivo and in vitro studies have linked the development of intimal hyperplasia to the abnormal hemodynamics and compliance mismatch. Therefore, it is essential to fully understand the relationship between the hemodynamics inside the coronary artery bypass and its mechanical and geometrical characteristics under the correct physiological conditions. In this work, hemodynamic of the bypass graft is studied numerically. The effect of the host and graft diameters ratio, the angle of anastomosis and the graft configuration on the local flow patterns and the distribution of wall shear stress are examined. The pulsatile waveforms boundary conditions are adopted from in vivo measurement data to study the hemodynamics of composite grafts namely Consequence and Y grafting in terms temporal and spatial distributions of the blood flows. Moreover, various non-Newtonian and Newtonian models of blood have been carried out to examine the numerical simulation of blood flow in stenosis artery. The results are presented and discussed for various operating conditions.

Elastin and collagen enhances electrospun aligned polyurethane as scaffolds for vascular graft

Mismatch in mechanical properties between synthetic vascular graft and arteries contribute to graft failure. The viscoelastic properties of arteries are conferred by elastin and collagen. In this study, the mechanical properties and cellular interactions of aligned nanofibrous polyurethane (PU) scaffolds blended with elastin, collagen or a mixture of both proteins were examined. Elastin softened PU to a peak stress and strain of 7.86 MPa and 112.28 % respectively, which are similar to those observed in blood vessels. Collagen-blended PU increased in peak stress to 28.14 MPa. The growth of smooth muscle cells (SMCs) on both collagen-blended and elastin/collagen-blended scaffold increased by 283 and 224 % respectively when compared to PU. Smooth muscle myosin staining indicated that the cells are contractile SMCs which are favored in vascular tissue engineering. Elastin and collagen are beneficial for creating compliant synthetic vascular grafts as elastin provided the necessary viscoelastic properties while collagen enhanced the cellular interactions.

Engineering a multimodal nerve conduit for repair of injured peripheral nerve

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.

Design and properties of a new hybrid stent-graft device

This PhD work explored a novel bio-inspired approach for designing artificial blood vessel implants known as stent-grafts. The design was inspired from body design of a caterpillar. This design concept induced natural flexibility and expandability property in the new stent-graft, which is considered critical in deciding long-term health of treated patients.

A new design concept for knitted external vein-graft support mesh

Autologous vein-graft failure significantly limits the long-term efficacy of coronary artery bypass procedures. The major cause behind this complication is biomechanical mismatch between the vein and coronary artery. The implanted vein experiences a sudden increase (10-12 fold) in luminal pressures. The resulting vein over-distension or 'ballooning' initiates wall thickening phenomenon and ultimate occlusion. Therefore, a primary goal in improving the longevity of a coronary bypass procedure is to inhibit vein over-distension using mechanical constriction. The idea of using an external vein-graft support mesh has demonstrated sustained benefits and wide acceptance in experimental studies. Nitinol based knitted structures have offered more promising mechanical features than other mesh designs owing to their unique loosely looped construction. However, the conventional plain knit construction still exhibits limitations (radial compliance, deployment ease, flexibility, and bending stresses) which limit this design from proving its real clinical advantage. The new knitted mesh design presented in this study is based on the concept of composite knitting utilising high modulus (nitinol and polyester) and low modulus (polyurethane) material components. The experimental comparison of the new design with a plain knit design demonstrated significant improvement in biomechanical (compliance, flexibility, extensibility, viscoelasticity) and procedural (deployment limit) parameters. The results are indicative of the promising role of new mesh in restoring the lost compliance and pulsatility of vein-graft at high arterial pressures. This way it can assist in controlled vein-graft remodelling and stepwise restoration of vein mechanical homoeostasis. Also, improvement in deployment limit parameter offers more flexibility for a surgeon to use a wide range of vein diameters, which may otherwise be rendered unusable for a plain knit mesh.

Assessment of acute burn management in 32 low- and middle-income countries

BACKGROUND: The purpose of this study is to ascertain whether acute burn management (ABM) is available at health facilities in low- and middle-income countries (LMICs). METHOD: The study used the World Health Organization situational analysis tool (SAT) which is designed to assess emergency and essential surgical care and includes data points relevant to the acute management of burns. The SAT was available for 1413 health facilities in 59 countries. RESULTS: A majority (1036, 77.5 %) of the health facilities are able to perform ABM. The main reasons for the referral of ABM are lack of skills (53.4 %) and non-functioning equipment (52.2 %). Considering health centres and district/rural/community hospitals that referred due to lack of supplies/drugs and/or non-functioning equipment, almost half of the facilities were not able to provide continuous and consistent access to the equipment required either for resuscitation or to perform burn wound debridement. Out of the facilities that performed ABM, 379 (36.6 %) are capable of carrying out skin grafts and contracture release, which is indicative of their ability to manage full thickness burns. However the magnitude of full thickness burns managed was limited in half of these facilities, as they did not have access to a blood bank. CONCLUSION: The initial management of acute burns is generally available in LMICs, however it is constrained by the inability to perform resuscitation (19 %) and/or burn wound debridement (10 %). For more severe burns, an inability to perform skin grafting or contracture release limits definitive management of full thickness burns, whilst lack of availability to blood further compromises the treatment of major burns.