A multilayered scaffold of a chitosan and gelatin hydrogel supported by a PCL core for cardiac tissue engineering

A three-dimensional scaffold composed of self-assembled polycaprolactone (PCL) sandwiched in a gelatin–chitosan hydrogel was developed for use as a biodegradable patch with a potential for surgical reconstruction of congenital heart defects. The PCL core provides surgical handling, suturability and high initial tensile strength, while the gelatin–chitosan scaffold allows for cell attachment, with pore size and mechanical properties conducive to cardiomyocyte migration and function. The ultimate tensile stress of the PCL core, made from blends of 10, 46 and 80 kDa (Mn) PCL, was controllable in the range of 2–4 MPa, with lower average molecular weight PCL blends correlating with lower tensile stress. Blends with lower molecular weight PCL also had faster degradation (controllable from 0% to 7% weight loss in saline over 30 days) and larger pores. PCL scaffolds supporting a gelatin–chitosan emulsion gel showed no significant alteration in tensile stress, strain or tensile modulus. However, the compressive modulus of the composite tissue was similar to that of native tissue (～15 kPa for 50% gelatin and 50% chitosan). Electron microscopy revealed that the gelatin–chitosan gel had a three-dimensional porous structure, with a mean pore diameter of ～80 μm, showed migration of neonatal rat ventricular myocytes (NRVM), maintained NRVM viability for over 7 days, and resulted in spontaneously beating scaffolds. This multi-layered scaffold has sufficient tensile strength and surgical handling for use as a cardiac patch, while allowing migration or pre-loading of cardiac cells in a biomimetic environment to allow for eventual degradation of the patch and incorporation into native tissue.     

Porous polycaprolactone scaffold for cardiac tissue engineering fabricated by selective laser sintering

An advanced manufacturing technique, selective laser sintering (SLS), was utilized to fabricate a porous polycaprolactone (PCL) scaffold designed with an automated algorithm in a parametric library system named the “computer-aided system for tissue scaffolds” (CASTS). Tensile stiffness of the sintered PCL strut was in the range of 0.43 ± 0.15 MPa when a laser power of 3 W and scanning speed of 150 in s^?1 was used. A series of compressive mechanical characterizations was performed on the parametric scaffold design and an empirical formula was presented to predict the compressive stiffness of the scaffold as a function of total porosity. In this work, the porosity of the scaffold was selected to be 85%, with micropores (40–100 μm) throughout the scaffold. The compressive stiffness of the scaffold was 345 kPa. The feasibility of using the scaffold for cardiac tissue engineering was investigated by culturing C2C12 myoblast cells in vitro for 21 days. Fluorescence images showed cells were located throughout the scaffold. High density of cells at 1.2 × 10⁶ cells ml^?1 was recorded after 4 days of culture. Fusion and differentiation of C2C12 were observed as early as 6 days in vitro and was confirmed with myosin heavy chain immunostaining after 11 days of cell culture. A steady population of cells was then maintained throughout 21 days of culturing. This work demonstrated the feasibility of tailoring the mechanical property of the scaffold for soft tissue engineering using CASTS and SLS. The macroarchitecture of the scaffold can be modified efficiently to fabricate scaffolds with different macropore sizes or changing the elemental cell design in CASTS. Further process and design optimization could be carried out in the future to fabricate scaffolds that match the tensile strength of native myocardium, which is of the order of tens of kPa.     

Mechanical properties of bioactive glass (13-93) scaffolds fabricated by robotic deposition for structural bone repair

There is a need to develop synthetic scaffolds to repair large defects in load-bearing bones. Bioactive glasses have attractive properties as a scaffold material for bone repair, but data on their mechanical properties are limited. The objective of the present study was to comprehensively evaluate the mechanical properties of strong porous scaffolds of silicate 13-93 bioactive glass fabricated by robocasting. As-fabricated scaffolds with a grid-like microstructure (porosity 47%, filament diameter 330 μm, pore width 300 μm) were tested in compressive and flexural loading to determine their strength, elastic modulus, Weibull modulus, fatigue resistance, and fracture toughness. Scaffolds were also tested in compression after they were immersed in simulated body fluid (SBF) in vitro or implanted in a rat subcutaneous model in vivo. As fabricated, the scaffolds had a strength of 86 ± 9 MPa, elastic modulus of 13 ± 2 GPa, and a Weibull modulus of 12 when tested in compression. In flexural loading the strength, elastic modulus, and Weibull modulus were 11 ± 3 MPa, 13 ± 2 GPa, and 6, respectively. In compression, the as-fabricated scaffolds had a mean fatigue life of ～10⁶ cycles when tested in air at room temperature or in phosphate-buffered saline at 37 °C under cyclic stresses of 1–10 or 2–20 MPa. The compressive strength of the scaffolds decreased markedly during the first 2 weeks of immersion in SBF or implantation in vivo, but more slowly thereafter. The brittle mechanical response of the scaffolds in vitro changed to an elasto-plastic response after implantation for longer than 2–4 weeks in vivo. In addition to providing critically needed data for designing bioactive glass scaffolds, the results are promising for the application of these strong porous scaffolds in loaded bone repair.     

Density–property relationships in collagen–glycosaminoglycan scaffolds

Collagen–glycosaminoglycan scaffolds for the regeneration of skin have previously been fabricated by freeze-drying a slurry containing a co-precipitate of collagen and glycosaminoglycan. The mechanical properties of the scaffold are low (e.g. the dry compressive Young’s modulus is roughly 30 kPa and the dry compressive strength is roughly 5 kPa). There is interest in using these scaffolds for tendon and ligament regeneration where there is a need for improved mechanical properties. Previous attempts to increase the mechanical properties of the scaffold by increasing the solid volume fraction of the scaffolds were limited by the increasing viscosity of the slurry, making it more difficult to mix and giving inhomogeneous scaffolds. Our recent work on mineralized collagen–glycosaminoglycan scaffolds used a vacuum filtration technique to increase the volume fraction of solids in the slurry, thereby increasing the density and mechanical properties of the scaffolds. In this work, we used this technique to fabricate collagen–glycosaminoglycan scaffolds with dry densities between 0.0076 and 0.0311 g cm^?3 and pore sizes between 250 and 350 μm, values appropriate for soft tissue growth. The compressive Young’s modulus and strength in the dry state increased from 32 to 127 kPa and from 5 to 19 kPa, respectively, with increasing density. The tensile Young’s modulus in the dry state increased from 295 to 3.1 MPa with increasing density. Finally, we showed that the attachment of cells onto the scaffold was directly proportional to the specific surface area of the scaffold, which defines the total internal surface area per volume of scaffold.     

Unique microstructural design of ceramic scaffolds for bone regeneration under load

During the past two decades, research on ceramic scaffolds for bone regeneration has progressed rapidly; however, currently available porous scaffolds remain unsuitable for load-bearing applications. The key to success is to apply microstructural design strategies to develop ceramic scaffolds with mechanical properties approaching those of bone. Here we report on the development of a unique microstructurally designed ceramic scaffold, strontium–hardystonite–gahnite (Sr–HT–gahnite), with 85% porosity, 500 μm pore size, a competitive compressive strength of 4.1 ± 0.3 MPa and a compressive modulus of 170 ± 20 MPa. The in vitro biocompatibility of the scaffolds was studied using primary human bone-derived cells. The ability of Sr–HT–gahnite scaffolds to repair critical-sized bone defects was also investigated in a rabbit radius under normal load, with β-tricalcium phosphate/hydroxyapatite scaffolds used in the control group. Studies with primary human osteoblast cultures confirmed the bioactivity of these scaffolds, and regeneration of rabbit radial critical defects demonstrated that this material induces new bone defect bridging, with clear evidence of regeneration of original radial architecture and bone marrow environment.     

Structure–function relationships and source-to-ground distance in electrospun polycaprolactone

The strength of electrospun scaffolds has direct relevance to their function within tissue engineering. We characterized the effects of source-to-ground distance on the mechanical properties of electrospun poly(ε-caprolactone) (PCL). Source-to-ground distances of 10, 15 and 20 cm, solids concentrations of 12 and 18 wt.% and mandrel rotation surface speeds of 0–12 m s^?1 were utilized. Tensile tests evaluated elastic modulus, tensile strength and elongation at failure. Scanning electron microscopy provided morphology and quantified fiber alignment. Increased source-to-ground distance yielded a microstructure allowing greater fiber rearrangement under load, tripling the observed tensile strength. Increases in rotational speed generally increased fiber alignment and strength at high but not low to moderate speeds. As fiber is quickly pulled out of a comparatively gentle falling process, collision with neighboring fibers moving at different speeds and in different directions can occur. The source-to-ground distance influences these collisions and thus has critical implications for microstructure and biocompatibility. In larger diameter (18 wt.% PCL), heavily point-bonded fibers (produced using a shorter, 10 cm source-to-ground distance), elongation at failure in the aligned direction increases dramatically due to severe localized necking. These specimens show only half of the tensile strength (from 2.6 to 4.5 MPa) and a dramatic increase (from 94% to 503%) in elongation at failure vs. a longer 20 cm source-to-ground distance. Strains of several hundred per cent are accompanied by periodic necking of large-diameter fibers in which microstructural failure appears to occur in a sequential manner involving an equilibrium between localized strain in the tensile direction and anisotropic point bonding that locally resists strain.     

Fabrication of HA/TCP scaffolds with a graded and porous structure using a camphene-based freeze-casting method

A room temperature camphene-based freeze-casting method was used to fabricate hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic scaffolds. By varying the solid loading of the mixture and the freezing temperature, a range of structures with different pore sizes and strength characteristics were achieved. The macropore size of the HA/TCP bioceramics was in the range of 100–200 μm, 40–80 μm and less than 40 μm at solid loadings of 10, 20 and 30 vol.%, respectively. The initial level of solid loading played a primary role in the resulting porosity of the scaffolds. The porosity decreased from 72.5 to 31.4 vol.% when the solid loading was increased from 10 to 30 vol.%. This resulted in an increase in the compressive strength from 2.3 to 36.4 MPa. The temperature gradient, rather than the percentage porosity, influenced the pore size distribution. The compressive strength increased from 1.95 to 2.98 MPa when samples were prepared at 4 °C as opposed to 30 °C. The results indicated that it was possible to manufacture porous HA/TCP bioceramics, with compressive strengths comparable to cancellous bone, using the freeze-casting manufacturing technique, which could be of significant clinical interest.     

Injectable and porous PLGA microspheres that form highly porous scaffolds at body temperature

Injectable scaffolds are of interest in the field of regenerative medicine because of their minimally invasive mode of delivery. For tissue repair applications, it is essential that such scaffolds have the mechanical properties, porosity and pore diameter to support the formation of new tissue. In the current study, porous poly(dl-lactic acid-co-glycolic acid) (PLGA) microspheres were fabricated with an average size of 84 ± 24 μm for use as injectable cell carriers. Treatment with ethanolic sodium hydroxide for 2 min was observed to increase surface porosity without causing the microsphere structure to disintegrate. This surface treatment also enabled the microspheres to fuse together at 37 °C to form scaffold structures. The average compressive strength of the scaffolds after 24 h at 37 °C was 0.9 ± 0.1 MPa, and the average Young’s modulus was 9.4 ± 1.2 MPa. Scaffold porosity levels were 81.6% on average, with a mean pore diameter of 54 ± 38 μm. This study demonstrates a method for fabricating porous PLGA microspheres that form solid porous scaffolds at body temperature, creating an injectable system capable of supporting NIH-3T3 cell attachment and proliferation in vitro.     

Characterization of a novel composite scaffold consisting of acellular bladder submucosa matrix,polycaprolactone and Pluronic F127 as a substance for bladder reconstruction

The bladder is an organ susceptible to a variety of congenital anomalies, injuries and disorders. To address the clinical limitations of existing scaffolds, we fabricated a novel scaffold that can be applied to morphological and functional bladder reconstruction. As a first step to prove the benefit of the scaffold, intensive in vitro and in vivo analyses were conducted. The novel composite scaffold was fabricated using polycaprolactone/Pluronic F127 (PCL/F127) and variable proportions (1, 3, 5 and 10 wt.%) of porcine acellular bladder submucosa matrix (BSM). Physicochemical properties and biocompatibilities of the scaffolds were characterized. For cell-mediated analysis, upper-urinary-tract-derived urine stem cells were used. Observations of tensile strength, modulus, porosity, cell adhesion, viability and proliferation characteristics of scaffolds indicated that the optimum proportion of BSM in the composite scaffolds was 3 or 5 wt.%. Based on comparison of 3 and 5 wt.% BSM/PCL/F127 scaffolds with respect to degradability, hydrophilicity, surface properties and functional group presence, the 3 wt.% BSM was chosen for in vivo studies. 8 weeks after kidney-subcapsular implantation of the 3 wt.% BSM/PCL/F127 scaffold, cells remained attached to the surface and there was no evidence of teratomas. A BSM content of 3 wt.% was the optimum proportion for fabrication of the neo scaffold. We predict that the 3 wt.% BSM/PCL/F127 composite scaffold could act as an ideal matrix after cystectomy based on its favorable physicochemical properties and biocompatibilities.     

Mesenchymal stem cell proliferation and differentiation on load-bearing trabecular Nitinol scaffolds

Bone tissue regeneration in load-bearing regions of the body requires high-strength porous scaffolds capable of supporting angiogenesis and osteogenesis. 70% porous Nitinol (NiTi) scaffolds with a regular 3-D architecture resembling trabecular bone were produced from Ni foams using an original reactive vapor infiltration technique. The “trabecular Nitinol” scaffolds possessed a high compressive strength of 79 MPa and high permeability of 6.9 × 10^?6 cm². The scaffolds were further modified to produce a near Ni-free surface layer and evaluated in terms of Ni ion release and human mesenchymal stem cell (hMSC) proliferation (AlamarBlue), differentiation (alkaline phosphatase activity, ALP) and mineralization (Alizarin Red S staining). Scanning electron microscopy was employed to qualitatively corroborate the results. hMSCs were able to adhere and proliferate on both as-produced and surface-modified trabecular NiTi scaffolds, to acquire an osteoblastic phenotype and produce a mineralized extracellular matrix. Both ALP activity and mineralization were increased on porous scaffolds compared to control polystyrene plates. Experiments in a model coculture system of microvascular endothelial cells and hMSCs demonstrated the formation of prevascular structures in trabecular NiTi scaffolds. These data suggest that load-bearing trabecular Nitinol scaffolds could be effective in regenerating damaged or lost bone tissue.     

Characterization of a biodegradable electrospun polyurethane nanofiber scaffold: Mechanical properties and cytotoxicity

The current study analyzes the biodegradation of a polycarbonate polyurethane scaffold intended for the growth of a tissue-engineered annulus fibrosus (AF) disc component. Electrospun scaffolds with random and aligned nanofiber configurations were fabricated using a biodegradable polycarbonate urethane with and without an anionic surface modifier (anionic dihydroxyl oligomer), and the mechanical behavior of the scaffolds was examined during a 4 week biodegradation study. Both the tensile strength and initial modulus of aligned scaffolds (σ = 14 ± 1 MPa, E = 46 ± 3 MPa) were found to be higher than those of random fiber scaffolds (σ = 1.9 ± 0.4 MPa, E = 2.1 ± 0.2 MPa) prior to degradation. Following initial wetting of the scaffold, the initial modulus of the aligned samples showed a significant decrease (dry: 46 ± 3 MPa; pre-wetted: 9 ± 1 MPa, p < 0.001). The modulus remained relatively constant during the remainder of the 4 week incubation period (aligned at 4 weeks: 8.0 ± 0.3 MPa). The tensile strength for aligned fiber scaffolds was affected in the same manner. Similar changes were not observed for the initial modulus of the random scaffold configuration. Biodegradation of the scaffold in the presence of cholesterol esterase (a monocyte derived enzyme) yielded a 0.5 mg week^–1 weight loss. The soluble and non-soluble degradation products were found to be non-toxic to bovine AF cells grown in vitro. The consistent rate of material degradation along with stable mechanical properties comparable to those of native AF tissue and the absence of cytotoxic effects make this polymer a suitable biomaterial candidate for further investigation into its use for tissue-engineering annulus fibrosus.     

Density–property relationships in mineralized collagen–glycosaminoglycan scaffolds

Mineralized collagen–glycosminoglycan scaffolds have previously been fabricated by freeze-drying a slurry containing a co-precipitate of calcium phosphate, collagen and glycosaminoglycan. The mechanical properties of the scaffold are low (e.g. the dry Young’s modulus for a 50 wt.% mineralized scaffold is roughly 780 kPa). Our previous attempt to increase the mechanical properties of the scaffold by increasing the mineralization (from 50 to 75 wt.%) was unsuccessful due to defects in the more mineralized scaffold. In this paper, we describe a new technique to improve the mechanical properties by increasing the relative density of the scaffolds. The volume fraction of solids in the slurry was increased by vacuum-filtration. The slurry was then freeze-dried in the conventional manner to produce scaffolds with relative densities between 0.045 and 0.187 and pore sizes of about 100–350 μm, values appropriate for bone growth. The uniaxial compressive stress–strain curves of the scaffolds indicated that the Young’s modulus in the dry state increased from 780 to 6500 kPa and that the crushing strength increased from 39 to 275 kPa with increasing relative density. In the hydrated state, the Young’s modulus increased from 6.44 to 34.8 kPa and the crushing strength increased from 0.55 to 2.12 kPa; the properties were further increased by cross-linking. The modulus and strength were well described by models for cellular solids.     

A three-layered electrospun matrix to mimic native arterial architecture using polycaprolactone,elastin, and collagen: A preliminary study

Throughout native artery, collagen, and elastin play an important role, providing a mechanical backbone, preventing vessel rupture, and promoting recovery under pulsatile deformations. The goal of this study was to mimic the structure of native artery by fabricating a multi-layered electrospun conduit composed of poly(caprolactone) (PCL) with the addition of elastin and collagen with blends of 45–45–10, 55–35–10, and 65–25–10 PCL–ELAS–COL to demonstrate mechanical properties indicative of native arterial tissue, while remaining conducive to tissue regeneration. Whole grafts and individual layers were analyzed using uniaxial tensile testing, dynamic compliance, suture retention, and burst strength. Compliance results revealed that changes to the middle/medial layer changed overall graft behavior with whole graft compliance values ranging from 0.8 to 2.8%/100 mm Hg, while uniaxial results demonstrated an average modulus range of 2.0–11.8 MPa. Both modulus and compliance data displayed values within the range of native artery. Mathematical modeling was implemented to show how changes in layer stiffness affect the overall circumferential wall stress, and as a design aid to achieve the best mechanical combination of materials. Overall, the results indicated that a graft can be designed to mimic a tri-layered structure by altering layer properties.     

Mechanical properties and dual drug delivery application of poly(lactic-co-glycolic acid) scaffolds fabricated with a poly(β-amino ester) porogen

Polymeric scaffolds that are biocompatible and biodegradable are widely used for tissue engineering applications. Scaffolds can be further enhanced by enabling the release of one or more drugs to stimulate regeneration or for the treatment of a specific disease or condition. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres were mixed with poly(β-amino ester) (PBAE) particles to create novel hybrid scaffolds capable of dual release of drug and growth factor. Fast-degrading PBAE particles loaded with the drug ketoprofen acted as porogens that provided a rapid 12 h release. The PLGA microspheres were loaded with a growth factor, bone morphogenetic protein 2, and fused together around the porogens to create a slow-degrading matrix that provided sustained release lasting 70 days. Drug release was further tailored by varying the amount of porogen added to the scaffold. Bioactivity measurements demonstrated that the scaffold fabrication technique did not damage the drug or protein. The compressive modulus was affected by the amount of porogen added, extending from 50 to 111 MPa for loadings from 60 to 40% PBAE, and after 5 days of degradation, it decreased to 0.6 to 1.1 kPa when the porogen was gone. PLGA containing a quick-degrading porogen can be used to release two drugs while developing a porous microarchitecture for cell ingrowth with in a matrix capable of maintaining a compressive modulus applicable for soft tissue implants.     

Combining micro computed tomography and three-dimensional registration to evaluate local strains in shape memory scaffolds

Appropriate mechanical stimulation of bony tissue enhances osseointegration of load-bearing implants. Uniaxial compression of porous implants locally results in tensile and compressive strains. Their experimental determination is the objective of this study. Selective laser melting is applied to produce open-porous NiTi scaffolds of cubic units. To measure displacement and strain fields within the compressed scaffold, the authors took advantage of synchrotron radiation-based micro computed tomography during temperature increase and non-rigid three-dimensional data registration. Uniaxial scaffold compression of 6% led to local compressive and tensile strains of up to 15%. The experiments validate modeling by means of the finite element method. Increasing the temperature during the tomography experiment from 15 to 37 °C at a rate of 4 K h⁻¹, one can locally identify the phase transition from martensite to austenite. It starts at ∼24 °C on the scaffolds bottom, proceeds up towards the top and terminates at ∼34 °C on the periphery of the scaffold. The results allow not only design optimization of the scaffold architecture, but also estimation of maximal displacements before cracks are initiated and of optimized mechanical stimuli around porous metallic load-bearing implants within the physiological temperature range.     

Modified PHBV scaffolds by in situ UV polymerization: Structural characteristic,mechanical properties and bone mesenchymal stem cell compatibility

An ideal scaffold provides an interface for cell adhesion and maintains enough biomechanical support during tissue regeneration. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) scaffolds with pore sizes ranging from 100 to 500 μm and porosity ～90% were prepared by the particulate-leaching method, and then modified by the introduction of polyacrylamide (PAM) on the inner surface of scaffolds using in situ UV polymerization, with the aim of enhancing the biological and mechanical properties of the PHBV scaffolds. The modified PHBV scaffolds had interconnected pores with porosity of 75.4–78.6% and pore sizes at peak volume from 20 to 50 μm. The compressive load and modulus were up to 62.45 N and 1.06 MPa, respectively. The water swelling percentage (WSP) of the modified PHBV scaffolds increased notably compared with that of the PHBV scaffolds, with the maximum WSP at 537%. Sheep bone mesenchymal stem cells (BMSC) were cultured on the PHBV and modified PHBV. The hydrophilic PAM chains did not influence BMSC viability or proliferation index, but the initial cell adhesion at 1 h of culture was enhanced significantly. Framing PHBV scaffold along with gel-like PAM chains inside is a novel model of inner surface modification for PHBV scaffolds, which shows potential in tissue engineering applications.     

Preparation of aligned porous gelatin scaffolds by unidirectional freeze-drying method

Porous gelatin scaffolds with microtubule orientation structure were manufactured by unidirectional freeze-drying technology, and their porous structure was characterized by scanning electron microscopy. Scaffolds with tunable pore size and high porosity up to 98% were obtained by adjusting the concentration of the gelatin solution and crosslinking agent during the preparation process. All the porous gelatin scaffolds exhibited oriented microtubule pores, with width and length from 50 to 100 μm and 100 to 500 μm, respectively. Meanwhile, the properties of the scaffolds, such as porosity, water adsorption ability and compressive strength, were studied. In vitro enzymatic degradation results showed that the absolute weight loss of the gelatin scaffolds exhibited an increasing trend from low to high gelatin concentration used to prepare gelatin scaffolds; in vitro cell culture results indicated that the porous gelatin scaffolds were non-toxic to cartilage cells, since the cells spread and grew well.     

Synthesis,characterization, and remodeling of weight-bearing allograft bone/polyurethane composites in the rabbit

The process of bone healing requires the restoration of both anatomy and physiology, and there is a recognized need for innovative biomaterials that facilitate remodeling throughout this complex process. While porous scaffolds with a high degree of interconnectivity are known to accelerate cellular infiltration and new bone formation, the presence of pores significantly diminishes the initial mechanical properties of the materials, rendering them largely unsuitable for load-bearing applications. In this study, a family of non-porous composites has been fabricated by reactive compression molding of mineralized allograft bone particles (MBPs) with a biodegradable polyurethane (PUR) binder, which is synthesized from a polyester polyol and a lysine-derived polyisocyanate. At volume fractions exceeding the random close-packing limit, the particulated allograft component presented a nearly continuous osteoconductive pathway for cells into the interior of the implant. By varying the molecular weight of the polyol and manipulating the surface chemistry of the MBP via surface demineralization, compressive modulus and strength values of 3–6 GPa and 107–172 MPa were achieved, respectively. When implanted in bilateral femoral condyle plug defects in New Zealand White rabbits, MBP/PUR composites exhibited resorption of the allograft and polymer components, extensive cellular infiltration deep into the interior of the implant, and new bone formation at 6 weeks. While later in vivo timepoints are necessary to determine the ultimate fate of the MBP/PUR composites, these observations suggest that allograft bone/polymer composites have potential for future development as weight-bearing devices for orthopedic applications.     

Structure and mechanical properties of β-TCP scaffolds prepared by ice-templating with preset ice front velocities

Anisotropic scaffolds with the typical structure of lamellar, aligned and continuous pores were successfully achieved by the directional solidification of water-based β-tricalcium phosphate (β-TCP) suspensions. Adjustable porosities from 49 to 82%, tunable pore widths from 8 to 50 μm and linked ceramic cells with wall thicknesses from 4 to 30 μm were obtained. Correlated compressive strengths reached from 0.4 MPa (82% porosity, low solidification velocity of 10 μm s⁻¹) to 40 MPa (49% porosity, high solidification velocity of 30 μm s⁻¹). At a given scaffold porosity, the compressive strength increased by more than twofold with increasing solidification velocity due to attendant structural changes. Thus, the key to controlling structural sizes, besides the trivial control of porosity through the water content in the initial suspension, is to control the solidification velocity. In this study, an analytical solution of the heat conduction equation was used as a novel approach to control the solidification velocity during the process. The relationships between processing conditions and resulting structure as well as between structure and mechanical properties were elucidated and discussed.     

Flexible and elastic porous poly(trimethylene carbonate) structures for use in vascular tissue engineering

Biocompatible and elastic porous tubular structures based on poly(1,3-trimethylene carbonate), PTMC, were developed as scaffolds for tissue engineering of small-diameter blood vessels. High-molecular-weight PTMC (M_n = 4.37 × 10⁵) was cross-linked by gamma-irradiation in an inert nitrogen atmosphere. The resulting networks (50–70% gel content) were elastic and creep resistant. The PTMC materials were highly biocompatible as determined by cell adhesion and proliferation studies using various relevant cell types (human umbilical vein endothelial cells (HUVECs), smooth muscle cells (SMCs) and mesenchymal stem cells (MSCs)). Dimensionally stable tubular scaffolds with an interconnected pore network were prepared by particulate leaching. Different cross-linked porous PTMC specimens with average pore sizes ranging between 55 and 116 μm, and porosities ranging from 59% to 83% were prepared. These scaffolds were highly compliant and flexible, with high elongations at break. Furthermore, their resistance to creep was excellent and under cyclic loading conditions (20 deformation cycles to 30% elongation) no permanent deformation occurred. Seeding of SMCs into the wall of the tubular structures was done by carefully perfusing cell suspensions with syringes from the lumen through the wall. The cells were then cultured for 7 days. Upon proliferation of the SMCs, the formed blood vessel constructs had excellent mechanical properties. Their radial tensile strengths had increased from 0.23 to 0.78 MPa, which is close to those of natural blood vessels.