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Biofabrication holds the potential to generate constructs that more closely recapitulate the complexity and heterogeneity of tissues and organs than do currently available regenerative medicine therapies. Such constructs can be applied for tissue regeneration or as in vitro 3D models. Biofabrication is maturing and growing, and scientists with different backgrounds are joining this field, underscoring the need for unity regarding the use of terminology. We therefore believe that there is a compelling need to clarify the relationship between the different concepts, technologies, and descriptions of biofabrication that are often used interchangeably or inconsistently in the current literature. Our objective is to provide a guide to the terminology for different technologies in the field which may serve as a reference for the biofabrication community.

Biofabrication holds the potential to generate constructs that more closely recapitulate the complexity and heterogeneity of tissues and organs than do currently available regenerative medicine therapies. Such constructs can be applied for tissue regeneration or as in vitro 3D models. Biofabrication is maturing and growing, and scientists with different backgrounds are joining this field, underscoring the need for unity regarding the use of terminology. We therefore believe that there is a compelling need to clarify the relationship between the different concepts, technologies, and descriptions of biofabrication that are often used interchangeably or inconsistently in the current literature. Our objective is to provide a guide to the terminology for different technologies in the field which may serve as a reference for the biofabrication community. Biofabrication holds great potential in the fields of regenerative medicine and physiological 3D in vitro models by allowing the manufacture of complex tissue constructs with a higher degree of biomimicry to native tissues than do current biomedical solutions.As the number of biofabrication technologies being developed continues to expand, it is of paramount importance to adopt a concerted terminology framework and avoid generalizations.The ratio between the spatial resolution and the timescale of manufacture could be considered as a reliable measure to aid in the selection of an appropriate biofabrication technology for a desired application.

Three-armed poly(trimethylene carbonate) macromers with a relatively high molecular weight of 28.9 kg mol(-1) are prepared by ring opening polymerization and subsequent functionalization with methacrylate end groups. A resin suitable for processing by stereolithography is developed using propylene carbonate as a diluent, a photoinitiator, and a dye to control the curing characteristics. The difficulties in building designed structures with digital light processing stereolithography and the ways of optimizing the resin compositions are described in detail. Using an optimized resin composition, which contained 50 wt% macromer, 50 wt% diluent, 0.05 wt% (relative to the macromer) dye, and 5 wt% (relative to the macromer) photoinitiator, designed 3D porous structures with a gyroid pore network geometry are manufactured. By varying pore sizes and porosities between, respectively, 300 and 1000 m and 60% and 90%, cylindrical porous poly(trimethylene carbonate) network structures with compression moduli of 85-2320 kPa are prepared. A porous poly(trimethylene carbonate) network meniscus implant is designed on the basis of computed tomography imaging data. By adjusting the characteristics of the gyroid pore architecture, an implant with a compression modulus close to 400 kPa, which fits the compression modulus of human meniscal tissue, is manufactured by stereolithography.

Mesenchymal stem cell (MSC) differentiation can be influenced by biophysical stimuli imparted by the host scaffold. Yet, causal relationships linking scaffold strain magnitudes and inlet fluid velocities to specific cell responses are thus far underdeveloped. This investigation attempted to simulate cell responses in a collagen–glycosaminoglycan (CG) scaffold within a bioreactor. CG scaffold deformation was simulated using μ-computed tomography (CT) and an in-house finite element solver (FEEBE/ linear ). Similarly, the internal fluid velocities were simulated using the afore-mentioned μCT dataset with a computational fluid dynamics solver (ANSYS/CFX). From the ensuing cell-level mechanics, albeit octahedral shear strain or fluid velocity, the proliferation and differentiation of the representative cells were predicted from deterministic functions. Cell proliferation patterns concurred with previous experiments. MSC differentiation was dependent on the level of CG scaffold strain and the inlet fluid velocity. Furthermore, MSC differentiation patterns indicated that specific combinations of scaffold strains and inlet fluid flows cause phenotype assemblies dominated by single cell types. Further to typical laboratory procedures, this predictive methodology demonstrated loading-specific differentiation lineages and proliferation patterns. It is hoped these results will enhance in-vitro tissue engineering procedures by providing a platform from which the scaffold loading applications can be tailored to suit the desired tissue.

We studied the in vivo performance of scaffolds consisting of nanofibrous poly(L-lactic acid) (P) and blend of poly(L-lactic acid/gelatin) (PG) prepared by electrospinning and further composited them with hydroxyapatite (HA) via alternate soaking method, to get poly(L-lactic acid)/hydroxyapatite (PH) and poly(L-lactic acid)/gelatin/hydroxyapatite (PGH) scaffolds respectively. The purpose of this study was to assess and compare bone regeneration potential of electrospun P, PG and electrospun-alternate soaked PH and PGH scaffolds using rat as an animal model by creating two 5 mm circular defects in calvaria. The respective scaffolds were implanted into the defects as one side implantation and both side implantation. Defects left empty served as a negative control for one side implantation and as sham control for both side implantations. The outcomes of the scaffold implantation were determined after 6 and 10 weeks by digital radiography, micro-CT, dual-energy X-ray absorptiometry (DEXA) and histological analysis. PGH scaffold regenerated maximum amount of new bone with high bone mineral density (BMD) into the defects and complete closure occurred in just 6 weeks while other scaffolds failed to close the defects completely. PGH group exhibited highest BMD value after 10 weeks. Histological findings showed abundant osteoblasts and initiation of matrix mineralization in HA containing scaffolds. Masson's trichrome staining showed collagen deposition in all scaffold groups except sham control group. Biochemical and haematological parameters were well with in normal range, indicating no infection due to scaffold implantation. These results prove PGH scaffold as a potential biomaterial for bone regenerative medicine.

Artificial tissue growth requires cells to proliferate and differentiate within the host scaffold. As cell function is governed by mechano-sensitive selection, tissue type is influenced by the microscopic forces exposed to the cells, which is a product of macroscopically straining the scaffold. Accordingly, the microscopic strain environment within a CG scaffold is offered here. Using μ CT to characterise CG scaffold architecture, two high-resolution 3D FE models were used to predict the deformation mechanics. While also providing an analysis of region-specific features, such as relative density, pore diameters and microstructural elastic stability, the deformation patterns afforded strains to be inferred for seeded cells. The results indicate a regional dependence, in terms of architectural and mechanical properties. Specifically, the peripheral regions demonstrated the lowest volume fraction, the highest stress concentrations and the greatest potential for elastic instability. Conversely, the mid-region exhibited the most homogeneous environment. Based on the proviso of mechano-sensitive proliferation and differentiation, the findings suggest cell function will vary between CG scaffold regions. Further work should investigate the possibility of improving the fabrication process in order to deliver a construct in line with the mid-region, or alternatively, isolation of the mid-region may prove beneficial for cell culturing.

Bolgen, Nimet/0000-0003-3162-0803; Bolgen, Nimet/0000-0003-3162-0803; Meydanli, E. Elif Guzel/0000-0001-9072-3322; KORKUSUZ, PETEK/0000-0002-7553-3915 WOS: 000269627700007 PubMed: 18690660 Biodegradable macroporous cryogels with highly open and interconnected pore structures were produced from dextran modified with oligo L-lactide bearing hydroxyethylmethacrylate (HEMA) end groups in moderately frozen solutions. Tissue responses to these novel scaffolds were evaluated in rats after dorsal subcutaneous implantation, iliac submuscular implantation, auricular implantation, or in calvarial defect model. In no case, either necrosis or foreign body reaction was observed during histological studies. The cryogel scaffolds integrated with the surrounding tissue and the formation of a new tissue were accompanied with significant ingrowth of connective tissue cells and new blood vessels into the cryogel. The tissue responses were significantly lower in auricular and calvarial implantations when compared with the subcutanous and the submuscular implantations. The degradation of the scaffold was slower in bone comparing to soft tissues. The biodegradable cryogels are highly biocompatible and combine extraordinary properties including having soft and elastic nature, open porous structure, and very rapid and controllable swelling. Therefore, the cryogels could be promising candidates for further clinical applications in tissue regeneration. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 91 A: 60-68, 2009 Turkish Scientific and Technological CouncilTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [105T509]; Turkish Academy of Sciences (TUBA)Turkish Academy of Sciences This study, which was performed in the contest of EU-FP6-NoE: Expertissues project and Graduate Programme of Hacettepe University (a part of Ph.D. thesis of Miss Nimet Bolgen under the supervision of Prof. Erhan Pisskin), was supported also by Turkish Scientific and Technological Council (Turkish Scientific and Technological Research Council, TUBITAK, Project: Tissuebiomed-105T509). Erhan Pis kin was also supported by Turkish Academy of Sciences (TUBA) as a full member. Nimet Bolgen has received a graduate student-scholarship from TUBITAK.