A macroscopic approach for stress-driven anisotropic growth in bioengineered soft tissues.

The simulation of growth processes within soft biological tissues is of utmost importance for many applications in the medical sector. Within this contribution, we propose a new macroscopic approach for modelling stress-driven volumetric growth occurring in soft tissues. Instead of using the standard approach of a-priori defining the structure of the growth tensor, we postulate the existence of a general growth potential. Such a potential describes all eligible homeostatic stress states that can ultimately be reached as a result of the growth process. Making use of well-established methods from visco-plasticity, the evolution of the growth-related right Cauchy-Green tensor is subsequently defined as a time-dependent associative evolution law with respect to the introduced potential. This approach naturally leads to a formulation that is able to cover both, isotropic and anisotropic growth-related changes in geometry. It furthermore allows the model to flexibly adapt to changing boundary and loading conditions. Besides the theoretical development, we also describe the algorithmic implementation and furthermore compare the newly derived model with a standard formulation of isotropic growth.

Development and Evaluation of a Tissue-Engineered Fibrin-based Canine Mitral Valve Three-dimensional Cell Culture System.

Myxomatous mitral valve disease is the most common cardiac disease of the dog, but examination of the associated cellular and molecular events has relied on the use of cadaveric valve tissue, in which functional studies cannot be undertaken. The aim of this study was to develop a three-dimensional (3D) cell co-culture model as an experimental platform to examine disease pathogenesis. Mitral valve interstitial (VIC) and endothelial (VEC) cells were cultured from normal and diseased canine (VIC only) valves. VICs were embedded in a fibrin-based hydrogel matrix and one surface was lined with VECs. The 3D static cultures (constructs) were examined qualitatively and semiquantitatively by light microscopy, immunofluorescence microscopy and protein immunoblotting. Some constructs were manipulated and the endothelium damaged, and the response examined. The construct gross morphology and histology demonstrated native tissue-like features and comparable expression patterns of cellular (α-smooth muscle actin [SMA] and embryonic smooth muscle myosin heavy chain [SMemb]) and extracellular matrix associated markers (matrix metalloproteinase [MMP]-1 and MMP-3), reminiscent of diseased valves. There were no differences between constructs containing normal valve VICs and VECs (type 1) and those containing diseased valve VICs and normal valve VECs (type 2). Mechanical manipulation and endothelial damage (type 3) tended to decrease α-SMA and SMemb expression, suggesting reversal of VIC activation, but with retention of SMemb+ cells adjacent to the wounded endothelium consistent with response to injury. Fibrin-based 3D mitral valve constructs can be produced using primary cell cultures derived from canine mitral valves, and show a phenotype reminiscent of diseased valves. The constructs demonstrate a response to endothelial damage indicating their utility as experimental platforms.

Growth factor-functionalized silk membranes support wound healing in vitro.

Chronic wounds represent a serious problem in daily medical routine requiring improved wound care. Silk of the domesticated silkworm (Bombyx mori) has been used to form a variety of biomaterials for medical applications. We genetically engineered B. mori to produce silk functionalized with growth factors to promote wound healing in vitro. In this study FGF-, EGF-, KGF-, PDGF- or VEGF-functionalized silk membranes were compared to native B. mori silk membranes without growth factors for their ability to support wound healing in vitro. All silk membranes were cytocompatible and supported macrophage secretion of neutrophil recruiting factor CXCL1 and monocyte chemoattractant protein 1 (MCP-1). VEGF-functionalized silk significantly outperformed other growth factor-functionalized silk membranes, but not native silk in angiogenesis assays. In addition, EGF- and VEGF-functionalized silk membranes slightly enhanced macrophage adhesion compared to silk without growth factors. In wound healing assays in vitro (reduction of wound lesion), dermal equivalents showed a higher wound healing capacity when covered with EGF-, FGF- or VEGF-functionalized silk membranes compared to native, KGF- or PDGF-functionalized silk membranes. Keratinocyte migration and growth is overstimulated by KGF- and VEGF-functionalized silk membranes. In conclusion, growth factor-functionalized silk membranes prepared from genetically engineered silk worm glands are promising wound dressings for future wound healing therapies.

[Materials/Biomaterials in Clinical Practice - a Short Review and Current Trends]. / Werkstoffe/Biomaterialien in der interventionellen und operativen Medizin ­ eine kurze Übersicht und aktuelle Trends.

Biomaterials play a major role in interventional medicine and surgery. However, the development of biomaterials is still in its early phases in spite of the huge progress made within the last decades. On the one hand, this is because our knowledge of the molecular and cellular processes associated with biomaterials is still increasing exponentially. On the other hand, a wide variety of advanced materials with highly interesting properties is being developed currently. This review provides a short introduction into the variety of materials in use as well as their application in interventional medicine and surgery. Also the importance of biomaterials for tissue engineering in the field of regenerative medicine and the functionalisation of biomaterials, including sterilisation methods are discussed. For the future, an even broader interdisciplinary scientific collaboration is necessary in order to develop novel biomaterials and facilitate their translation into clinical practice.

Laparotomy closure using an elastic suture: a promising approach.

BACKGROUND: Midline laparotomy wound failure like burst abdomen remains one of the major complications after abdominal surgery. The use of sutures with a closer resemblance to abdominal wall physiology, like elastic threads, could decrease the risk of these complications occurring. Thus, we evaluated the possibility of using a new elastic thread composed of thermoplastic polyurethane (TPU) as a suture for the closure of midline laparotomies compared to conventionally used polypropylene (PP) in a rabbit model. METHODS: The elastic TPU thread was processed and tensile tests were performed. Twenty female chinchilla rabbits underwent midline laparotomy. They were randomized to a TPU and a PP group depending on the suture used for fascia closure. After 7 or 21 days, the abdominal walls were assessed macroscopically for wound healing complications and were explanted for histopathological investigation. RESULTS: Tensile tests showed a mean elastic elongation of 55.5% and a sufficient material strength of the TPU thread. In animal experiments, there was no difference between the groups at 7 days; however, the TPU suture showed significantly less CD68 positive cells (p < 0.001) and a higher collagen I/III ratio (p = 0.011) than PP did after 21 days. The amount of apoptotic cells was significantly elevated in the TPU group (p = 0.007) after 21 days. No differences were found concerning granuloma size and number of Ki67-positive cells. CONCLUSIONS: The newly developed TPU thread shows promising tensile characteristics. Midline laparotomy closure is feasible and safe in a rabbit model. Immunohistochemistry indicates similar biocompatibility and wound healing after implantation compared to PP after 21 days. To confirm these findings and to proof long-term capability further studies need to be conducted.

[In vitro and in vivo investigations of a modified textile keratoprosthesis. ACTO TexKPRO]. / In-vitro- und In-vivo-Untersuchung einer modifizierten textilen Keratoprothese. ACTO TexKPRO.

BACKGROUND: Clinical application of a keratoprosthesis (KPRO) is still a challenging task. Recent developments reflect the concepts of nut and bolt, intrastromal implantation or an osteoodontokeratoprosthesis (OOKP). A new concept of a textile KPRO has been evaluated in a limited human study with considerable difficulties which after termination of the study and considerable improvements was restarted using animal experiments. MATERIALS: The ACTO TexKPRO is made from polyvinylidene difluoride (PVDF) fibers and transparent silicone. The first and second developmental stages differed in density and size of fibers and furthermore in surface modifications of the fibers and optics which were improved for the second prototype. METHODS: Implantation of the prosthesis was performed in four patients with corneal blindness and in two cases retinal disease which required surgery. In the later animal experiments surgery was performed on three rabbits. Surgery was performed by redressing the conjunctiva, opening of the eyeball with a central 6.5 mm trephination, removal of the lens and iris and implantation and suturing of the TexKPRO. If required a silicone oil endotamponade was placed. RESULTS: All eyes were stable with the keratoprosthesis. The first prototype showed conjunctival recession on the textile haptics with highly susceptible endopthalmitis risk due to infection of the PVDF so that we decided to remove the prosthesis from all eyes after one case of severe endophthalmitis occurred. The longest time of placement was 40 months and the shortest time 6 months. All eyes were restored by keratoplasty. In animals with the new haptic we found better conjunctivalization and stable implantation of the KPRO. DISCUSSION: The textile KPRO provides a stable implantation procedure and safe connection of fibers to the scleral wound bed. The optical and mechanical implantation is safe and stable. Surface epithelialization is improved with the new surface modifications and different PVDF fiber density but beforel new implantations are planned further conceptual changes will be introduced.

Surgical management of retro-aortic left renal vein in combined abdominal aortic and coronary surgery.

Although generally retro-aortic left renal vein is a rare anatomic finding, it occurs in 0.8% of the patients admitted for abdominal aortic aneurysm surgery. Surgeons fear fatal bleeding during clamping of the aorta, caused by a more caudal insertion of the retro-aortic left renal vein and a greater vulnerability of the anomalous tissue. Once such a complication occurs, a reconstruction of the retro-aortic left renal vein using a synthetic graft should be performed to obtain adequate renal venous flow and maintain renal function.