Journal of Tissue Science and Engineering

We present a case report using this inlay resurfacing prosthesis as a salvage procedure in a 37 year old man with a large trochlea defect after 6 former cartilage procedures. The early follow-up results after treatment with this customized metal mini-prosthesis in a challenging young active patient with a focal (osteo) chondral lesions and a history of failed previous cartilage surgery demonstrated significant pain and subjective outcome improvements at 4 years.

Fluorescent dyes such as PKH26 and VybrantDil facilitate rapid and simple labeling of cells for later detection in various assays. But covering the cell surface with lipophilic fluorescent dyes may impair cellular functions. We therefore investigated the effects of PKH26 and VybrantDil on viability, proliferation, differentiation, attachment and migration of human mesenchymal stromal cells (MSCs) in vitro. To this end, MSCs were harvested from bone marrow of 12 individuals, expanded employing methods compliant to good manufacturing practice, and stained with PKH26 or VybrantDil. MSCs without label served as controls. The intensity of fluorescent staining as function of label and incubation time was investigated. Viability and proliferation were enumerated by cell counting. The osteogenic and adipogenic differentiations of MSCs were explored by cytochemical staining and transcript analyses, the cell migration and attachment by specific in vitro assays. We report that labeling of human MSCs with PKH26 yielded brighter signals facilitating prolonged detection compared to VybrantDil. No significant effects of PKH26 and VybrantDil were recorded when the viability, proliferation, attachment, osteogenic and adipogenic differentiation of human MSCs were investigated. But loading cells with PKH26 or VybrantDil significantly diminished the migration of the MSCs in vitro. We conclude that analyses depending on cellular migration may be biased when the cells are loaded with these lipophilic dyes.

Biofabrication as an interdisciplinary area is fostering new knowledge and integration of areas like nanotechnology, chemistry, biology, physics, materials science, control systems, among many others, necessary to accomplish the challenge of bioengineering functional complex tissues. The emergence of integrated platforms and systems biology to understand complex biological systems in multiscale levels will enable the prediction and creation of biofabricated biological structures. This systematic analysis (meta-analysis) or integrated platforms for estimating biological process have been named as BioCAE, which will become the key for important steps of the biofabrication processes. Biological Computational Aided Engineering (BioCAE) is a new computational approach to understanding and bioengineer complex tissues (biofabrication) using a combination of different methods as multiscale modelling, computer simulations, data mining and systems biology. In addition, multi-agent systems (MAS), which are composed of different interacting computing entities called agents, also provide an interesting way to design and implement simulations of biological systems, integrating them with all steps of the BioCAE. MAS as a part of computational science have become a growing area to manipulate and solve complex problems. This paper presents an approach that will allow predicting the development and behavior of different biological processes such as molecular networks, gene interactions, cells, tissues and organs due to its flexibility, beyond to provide a new outlook in the biofabrication of tissues and organs.

Skin healing a complex and well-orchestrated process that involves the coordination and activity of many cell types. Myeloid lineage cells are inflammatory cells recruited to the wound site that remove injured tissue and invading pathogens. Besides this role, due to their ability to secrete a variety of growth factors and cytokines, myeloid cells influence each stage of wound healing (primarily inflammation and proliferation phases). Abnormalities in myeloid cell function lead to pathologies such as excessive and deficient healing. Therapies based on modulating myeloid cells may hold therapeutic potential. However, further research is needed to fully elucidate the spatial and temporal mechanisms of myeloid cells in skin healing. The objective of this review is to discuss recent findings on the role of myeloid lineage cells in skin healing and regeneration.

Various cell-based therapies use the transplantation of ex vivo cultured chondrocytes or stem cells to support repair of cartilage defects. Cell expansion in vitro is required prior to transplantation accompanied by cell dedifferentiation, resulting in unwanted fibrocartilage formation in vivo. Targeted application of growth factors during in vitro cultivation is intended to enhance chondrogenic differentiation of cells. In previous studies, collagen-based scaffolds enriched with silica particles coupled with the insulin-like growth factor (IGF) 1 were tested, concerning their suitability to increase the in vitro redifferentiation of human chondrocytes. Accordingly, in the present study chondrogenic differentiation potential of IGF-1-coupled particles was investigated using human chondrocytes cultured in scaffold-free spheroid pellet culture. Further, influence of IGF-1-coupled particles on mesenchymal stem cells derived from bone marrow (BM-MSCs) cultured onto collagen–based scaffold or in pellet culture was examined as well pellet culture was examined. Chondrogenic differentiation was induced by the growth factor IGF-1 applied as I) soluble IGF-1 or II) conjugated to red fluorescent silica particles. In addition, control silica particles conjugated with NH2 were used to exclude adverse side effects. Besides cell proliferation, collagen type II and glycosaminoglycan synthesis was quantified and histological staining performed to investigate the chondrogenic differentiation. In pellet culture, IGF-1-coupled particles were applied during the pellet formation only. Traceable red fluorescent particles showed homogenous distribution within the pellets. Adverse effects were not detected. Human chondrocyte pellets displayed significantly increased collagen type II synthesis using IGF-1-coupled particles, compared to soluble IGF-1. Independent of the application mode, induction of chondrogenic differentiation of BM-MSCs cultured in pellets was not suitable with the addition of IGF-1 only. However, BM-MSCs cultivation onto collagen-based scaffold enriched with IGF-1-coupled particle showed superior glycosaminoglycan synthesis, compared to soluble IGF-1 application. Using IGF-1 coupled to particles within a three-dimensional matrix resulted in an increased stimulatory chondrogenic effect, indicating a promising tool for controlled growth factor delivery during treatment of cartilage lesion.

Background: Endocardial infusion is a minimally invasive procedure for cell delivery with good selectivity to the target region. However, certain limitations to current devices could affect the precision of the procedure and the therapeutic outcome. Therefore, we developed an enhanced device for transendocardial cell infusion. Methods and Results: Our device is based on an electrode-guided transendocardial bidirectional 75 cm long catheter and 0.5 mm diameter inner needle. The key advantages of our device are the slender catheter diameter (7 Fr), consistent needle tip length, regulation of the catheter angle and independence between the needle and catheter. Mesenchymal stem cells (MSCs) were obtained from the inguinal adipose tissue of six healthy swine and propagated through 2-3 passages. Using the catheter, pre-labeled MSCs were infused autogenously into the swine hearts. The MSCs-infused myocardial regions were harvested on the infusion day (day 0) or 2 days later, and histological analysis was performed. The MSCs were successfully infused into all six swine myocardia and distributed along the hole made by the needle. The spread area of MSCs was larger at 2 days after infusion than at day 0 (1.38 ± 0.26 vs. 0.51 ± 0.17 mm2/infusion, p=0.013). No complications occurred during the procedure, such as cardiac tamponade or arrhythmia. Conclusion: These results demonstrate that our enhanced device could be useful for delivering cells into the myocardium.