Macroporous Scaffolds Research Articles

Correction: A testis-derived macroporous 3D scaffold as a platform for the generation of mouse testicular organoids

Correction for 'A testis-derived macroporous 3D scaffold as a platform for the generation of mouse testicular organoids' by Tohid Rezaei Topraggaleh et al., Biomater. Sci., 2019, 7, 1422-1436, DOI: 10.1039/C8BM01001C.

Study on Polycaprolactone Coated Hierarchical Meso/ Macroporous Titania Scaffolds for Bone Tissue Engineering

In this study, the effect of polycaprolactone (PCL) coating on the mechanical strength, cell behavior and cell attachment of the hierarchical meso/macroporous Titania scaffold were investigated. Titania scaffold as the substrate was fabricated through the evaporation-induced self-assembly coupled with the foamy method. Then prepared scaffolds were coated by polycaprolactone solution with three different weight percentages by the dip-coating method. SAXS, WAXRD, SEM, compressive strength, MTT and cell attachment test were applied to characterized the samples. Based on XRD results, as polycaprolactone concentration increased, the intensity of the crystalline polycaprolactone phase increased while the TiO2 peak intensity decreased due to the covering of mesoporous titania by polycaprolactone. Compressive strength showed that by increasing polycaprolactone percent, the porosity decrease from 89.5 to 73.8 % which caused increasing strength from 0.2 to 0.79 MPa. The SEM results illustrated that by increasing polycaprolactone concentration from 1.2 to 1.5 wt%, the macrospores were filled by polycaprolactone. In this regard, The sample containing 1wt% polycaprolactone was choosen as the selective sample. Also, the MTT test reported a small trace of cytotoxicity in contact with the L929 mouse fibroblast cells. The cell attachment test that was performed by using MG63 cells, showed that the coated samples provided the suitable substrate for cells to attach and also showed cell viability on the surface of the coated substrate. Overall, according to the results, the hierarchical meso/macroporous Titania scaffold coated with 1 wt% polycaprolactone, could have good potential to be used in tissue engineering.

Applications of electrospun scaffolds with enlarged pores in tissue engineering.

Despite electrospinning having multiple advantages over other methods such as creating materials with a superfine fiber diameter, high specific surface area, and good mechanical properties, the pore diameter of scaffolds prepared directly using conventional electrospinning is often smaller than a few tens of microns, which may not be suitable for three-dimensional (3-D) cell culture and tissue growth. In order to achieve satisfactory results for use in tissue engineering, the pore size of the scaffold should be increased to a size dependent on the specific cells being cultured. Many methods for enlarging the pore size of electrospun scaffolds have been described in the literature. In the present review, we have summarized the preparation of macroporous electrospun scaffold techniques for the skin, blood vessels, bone, cartilage and nerve tissue engineering for different applications, and further discuss the influence of changing pore-enlarging process parameters on the properties of the scaffolds, such as mechanical properties, and hydrophilicity and hydrophobicity, etc. We believe that changes in scaffold pore size and related physical properties can have a profound impact on cell behavior, such as adhesion, proliferation and infiltration, and the significance of their influence on applications of electrospun tissue engineering scaffolds is worthy of further investigation in the future.

Decellularized liver ECM-based 3D scaffolds: Compositional, physical, chemical, rheological, thermal, mechanical, and in vitro biological evaluations

The extracellular matrix (ECM) is involved in many critical cellular interactions through its biological macromolecules. In this study, a macroporous 3D scaffold originating from decellularized bovine liver ECM (dL-ECM), with defined compositional, physical, chemical, rheological, thermal, mechanical, and in vitro biological properties was developed. First, protocols were determined that effectively remove cells and DNA while ECM retains biological macromolecules collagen, elastin, sGAGs in tissue. Rheological analysis revealed the elastic properties of pepsin-digested dL-ECM. Then, dL-ECM hydrogel was neutralized, molded, formed into macroporous (~100–200 μm) scaffolds in aqueous medium at 37 °C, and lyophilized. The scaffolds had water retention ability, and were mechanically stable for at least 14 days in the culture medium. The findings also showed that increasing the dL-ECM concentration from 10 mg/mL to 20 mg/mL resulted in a significant increase in the mechanical strength of the scaffolds. The hemolysis test revealed high in vitro hemocompatibility of the dL-ECM scaffolds. Studies investigating the viability and proliferation status of human adipose stem cells seeded over a 2-week culture period have demonstrated the suitability of dL-ECM scaffolds as a cell substrate. Prospective studies may reveal the extent to which 3D dL-ECM sponges have the potential to create a biomimetic environment for cells.

On the Evaluation of a Novel Hypoxic 3D Pancreatic Cancer Model as a Tool for Radiotherapy Treatment Screening.

Simple SummaryPancreatic cancer challenges global health with non-specific symptoms, devastatingly low survival rates, and high treatment resistance profiles. Tissue engineering is advancing to facilitate animal free tissue biomimicry, allowing the replication of tumour tissue specific hallmarks of pancreatic cancer that challenge modern treatments. Here, we report the development and characterisation of a low oxygen (hypoxic) 3D polyurethane scaffold system for long-term analysis of radiation responses. This finely tuned platform more accurately recapitulates bio-physical, bio-chemical, and structural-bio-mechanical in vivo tissue niches as well as tumour hypoxia. The latter is a treatment-limiting feature for radiotherapy, allowing the system to streamline the transition of clinical testing from bench to bedside.Tissue engineering is evolving to mimic intricate ecosystems of tumour microenvironments (TME) to more readily map realistic in vivo niches of cancerous tissues. Such advanced cancer tissue models enable more accurate preclinical assessment of treatment strategies. Pancreatic cancer is a dangerous disease with high treatment resistance that is directly associated with a highly complex TME. More specifically, the pancreatic cancer TME includes (i) complex structure and complex extracellular matrix (ECM) protein composition; (ii) diverse cell populations (e.g., stellate cells), cancer associated fibroblasts, endothelial cells, which interact with the cancer cells and promote resistance to treatment and metastasis; (iii) accumulation of high amounts of (ECM), which leads to the creation of a fibrotic/desmoplastic reaction around the tumour; and (iv) heterogeneous environmental gradients such as hypoxia, which result from vessel collapse and stiffness increase in the fibrotic/desmoplastic area of the TME. These unique hallmarks are not effectively recapitulated in traditional preclinical research despite radiotherapeutic resistance being largely connected to them. Herein, we investigate, for the first time, the impact of in vitro hypoxia (5% O2) on the radiotherapy treatment response of pancreatic cancer cells (PANC-1) in a novel polymer (polyurethane) based highly macroporous scaffold that was surface modified with proteins (fibronectin) for ECM mimicry. More specifically, PANC-1 cells were seeded in fibronectin coated macroporous scaffolds and were cultured for four weeks in in vitro normoxia (21% O2), followed by a two day exposure to either in vitro hypoxia (5% O2) or maintenance in in vitro normoxia. Thereafter, in situ post-radiation monitoring (one day, three days, seven days post-irradiation) of the 3D cell cultures took place via quantification of (i) live/dead and apoptotic profiles and (ii) ECM (collagen-I) and HIF-1a secretion by the cancer cells. Our results showed increased post-radiation viability, reduced apoptosis, and increased collagen-I and HIF-1a secretion in in vitro hypoxia compared to normoxic cultures, revealing hypoxia-induced radioprotection. Overall, this study employed a low cost, animal free model enabling (i) the possibility of long-term in vitro hypoxic 3D cell culture for pancreatic cancer, and (ii) in vitro hypoxia associated PDAC radio-protection development. Our novel platform for radiation treatment screening can be used for long-term in vitro post-treatment observations as well as for fractionated radiotherapy treatment.

Biofunctional micro/nanostructured “volcano-like” layer-coated 3D porous Ti-10Ta-2Nb-2Zr scaffolds improve osteogenesis and osseointegration for dental implants in vitro and in vivo

Ti-10Ta-2Nb-2Zr (TTNZ) alloy has been previously suggested to be a promising alternate biomaterial for implant applications. However, its mismatch in elastic modulus with human bone and its lack of sufficient bioactivity are two concerns that need to be addressed further. In this study, for the first time, we attempted to use macroporous structures on TTNZ alloy scaffolds manufactured by selective laser melting (SLM) to reduce their modulus of elasticity and strengthen bone interlocking. Then, we modified scaffold surfaces with hydroxyapatite (HA) coating by microarc oxidation (MAO) to promote osseointegration. The microstructure, surface morphology, chemical composition, mechanical properties, biological activities and osteogenesis performance of this scaffold were systematically investigated in vitro and in vivo. The results revealed that scaffolds with this novel porous alloy possess a lower elastic modulus than solid structures. A micro/nanostructured layer with HA was successfully formed, which was verified by scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and energy dispersive spectroscopy (EDS). At the same time, this surface has increased hydrophilicity and roughness compared to unmodified surfaces and commercial pure titanium (CP-Ti). Furthermore, in vitro studies found that compared with MAOTTNZ samples with lower porosity, bare TTNZ samples, and CP-Ti samples, MAOTTNZ with adequate porosity could improve protein adsorption, cell proliferation, adhesion, alkaline phosphatase (ALP) activity and osteogenesis-related gene expression. In vivo studies, including those in which microcomputerized tomography, histological examination and biomechanical testing of macroporous MAOTTNZ scaffolds were performed, demonstrated that the formation of new bones was significantly boosted in rabbits after implantation. Consequently, this research presents an option for conventional titanium alloys with improved osteogenesis and osseointegration that could be used in further dental implant applications. • A 3D-printed porous implant with a novel nontoxic TTNZ alloy was developed. • A bioactive volcano-like HA coating was prepared on macroporous TTNZ scaffold. • The new micro/nanostructured surface showed high hydrophilicity and roughness. • The MAO-modified/porous TTNZ composite promotes osteogenesis and osseointegration.

Tuning Physicochemical Properties of a Macroporous Polysaccharide-Based Scaffold for 3D Neuronal Culture.

Central nervous system (CNS) lesions are a leading cause of death and disability worldwide. Three-dimensional neural cultures in biomaterials offer more physiologically relevant models for disease studies, toxicity screenings or in vivo transplantations. Herein, we describe the development and use of pullulan/dextran polysaccharide-based scaffolds for 3D neuronal culture. We first assessed scaffolding properties upon variation of the concentration (1%, 1.5%, 3% w/w) of the cross-linking agent, sodium trimetaphosphate (STMP). The lower STMP concentration (1%) allowed us to generate scaffolds with higher porosity (59.9 ± 4.6%), faster degradation rate (5.11 ± 0.14 mg/min) and lower elastic modulus (384 ± 26 Pa) compared with 3% STMP scaffolds (47 ± 2.1%, 1.39 ± 0.03 mg/min, 916 ± 44 Pa, respectively). Using primary cultures of embryonic neurons from PGKCre, Rosa26tdTomato embryos, we observed that in 3D culture, embryonic neurons remained in aggregates within the scaffolds and did not attach, spread or differentiate. To enhance neuronal adhesion and neurite outgrowth, we then functionalized the 1% STMP scaffolds with laminin. We found that treatment of the scaffold with a 100 μg/mL solution of laminin, combined with a subsequent freeze-drying step, created a laminin mesh network that significantly enhanced embryonic neuron adhesion, neurite outgrowth and survival. Such scaffold therefore constitutes a promising neuron-compatible and biodegradable biomaterial.

Composition-controlled degradation behavior of macroporous scaffolds from three-armed biodegradable macromers

Acidification of implant microenvironment and inflammation due to degradation products of high molecular weight poly(α‑hydroxy acids) like PLA and PLGA is a risk that can limit their use in regenerative medicine, tissue engineering and drug delivery. We developed macromers that consist of a three-armed core with varying degrees of ethoxylation, hydrolytically degradable oligolactide blocks and terminal methacrylate groups (TriLA macromers) for cross-polymerization into monolithic or macroporous structures. Within the macromer platform, biophysical and biochemical properties can be adjusted by macromer chemistry. In this work, eight new macromer types with a reduced degree of methacrylation or substitution of a fraction of the lactic acid units with glycolic acid were successfully synthesized starting from a fully methacrylated, oligolactide-based TriLA macromer. Chemical characterization confirmed feed-dependent glycolic acid integration and controlled reduction in degree of methacrylation. The degradation behavior of macroporous scaffolds made by solid lipid templating from both the previously established and the new macromers was systematically investigated. In general, the scaffolds displayed continuous mass loss over time when the onset time of degradation was passed. Depending on arm length as well as hydrophilicity of the oligomeric building blocks, degradation half-life ranged from 3 to 4 weeks to over 81 weeks. Glycolic acid integration accelerated network degradation more effectively than an increase in core molecule hydrophilicity. The observed, adjustable degradation profiles with only moderate medium acidification and a dominant phase of almost linear mass loss make this material platform promising for regenerative and drug delivery applications.

Three-dimensional (3D), macroporous, elastic, and biodegradable nanocomposite scaffold for in situ bone regeneration: Toward structural, biophysical, and biochemical cues integration

Although bone tissue with remarkable healing capabilities, the rapid and successful bone regeneration continues to present a challenge because that the influence factors for bone healing are multifaceted, especially for massive bone defects. From a cell/material interactions point of view, integrating multiple cues into one biomaterial is considered as a promising approach in the clinical treatment of bone defects thanks to the provided multiple stimuli. Herein, 3D macroporously elastic biodegradable nanocomposite bone scaffolds (PCSG) were successfully developed based on poly(citrate-siloxane) (PCS) hybrid elastomer and reduced graphene oxide (rGO). The PCSG scaffolds combine with structure (3D, largely open and interconnected pore architecture, high porosity), biophysics (high mechanical properties, roughness surface, piezoelectricity property), and biochemistry cues (silica cross-linked network, Si ions release). Experiments demonstrate that the structurally, biophysically, and biochemically biomimetic properties of PCSG scaffolds are beneficial for triggering cell adhesion, proliferation, matrix mineralization , osteogenic differentiation of osteoblasts (MC3T3-E1) in vitro and significantly promoting in situ bone regeneration in a calvarial bone defect model. The effective and simple strategy of multiple cues integration could pave a universally applicable way in development of bone tissue engineering biomaterials with good osteoinductivity and osteoconductivity for large defects repair, and the reported PCSG scaffolds demonstrate the potential clinic application in fields of bone regeneration and 3D culture of cells. • Integrating structure, biophysics, and biochemistry cues into one bone scaffold for in situ bone regeneration. • The fabrication of 3D bone scaffold with largely open and porosity via the facile sol-gel method. • The proposed bone scaffolds with super Young's modulus not only in dry state but in hydrated condition.

Ethanol fermentation using macroporous monolithic hydrogels as yeast cell scaffolds

Ethanol fermentation with a hybrid system containing free and immobilized yeast cells on a macroporous monolithic hydrogel scaffold was investigated. Cell immobilization was achieved using N-isopropylacrylamide (NIPA) and methoxy triethyleneglycol acrylate (MTGA) hydrogels having macroporous monolithic structures containing interconnected micrometer-sized macropores. The immobilized cells grow within the hydrogel and can exit through the macropores into the fermentation medium, and thus a hybrid bioreactor consisting of free and immobilized yeast cells is constructed. The transformation of d-glucose to ethanol using Saccharomyces cerevisiae in batch and continuous fermentation processes was examined. Ethanol was successfully fermented using the macroporous hydrogels, whereas the conventional nonporous NIPA hydrogel does not effectively act as a cell scaffold. In continuous fermentation, the hybrid system containing both free yeast cells and those immobilized in the macroporous MTGA hydrogel showed higher ethanol productivity than the control system containing only free cells. Crucially, the macroporous hydrogel allowed the stable growth of immobilized yeast cells, resulting in a high cell density in the reactor. The hybrid system under steady-state fermentation had free and immobilized cell densities of 1.72 kg-free-cell/m3 and 29 kg-immobilized-cell/m3-gel, respectively, and the ethanol productivities 0.421 kg-ethanol/(kg-free-cell·h) and 0.128 kg-ethanol/(kg-immobilized-cell·h), respectively.

The vascular clock: a new insight into endothelial cells and pericytes crosstalk

Abstract Background/Introduction Circadian rhythms, defined as biological oscillations with a period of circa 24h, regulate many physiological processes in the cardiovascular system, such as vascular function, vascular tone, blood pressure, heart rate and thrombus formation [1]. The vasculature responds to the main pacemaker located in the brain, but it also possesses its own clock. Indeed, a molecular clock has been identified in endothelial cells (EC) and smooth muscle cells (SMC). The disruption of the circadian clock profoundly affects cardiovascular functionality with adverse cardiovascular events such as myocardial infarction or stroke showing a 24h rhythmicity with a peak incidence in the early morning. Among several mechanisms affected by circadian dysregulation, angiogenesis plays a fundamental role in homeostasis and development of new blood vessels. EC and pericytes (PC) are the two main cell populations in the capillaries, and their physical and paracrine interaction drives and regulates the sprouting. However, the presence and the role of circadian rhythms in pericytes and whether the molecular clock affects the endothelial/pericyte interactions remain unexplored. Purpose The aim of this study is to identify a molecular clock in human vascular pericytes and elucidate the impact of the circadian clock on the formation of new blood vessels. Methods Human primary PC were synchronised and the rhythmicity of clock genes measured by luminescence, immunofluorescence, and qPCR. Synchronised PC were co-cultured with Bmal1::LUC human primary EC. The effect of PC synchronisation and circadian clock disruption by shRNA on EC clock genes and angiogenic potential were measured by luminescence and Matrigel assay, respectively. A macroporous polyurethane scaffold was developed for 3D co-cultures. Results PC presented rhythmic expression of the principal circadian genes with a circa 24h period but in our experimental setting, EC did not show circadian rhythmicity. Synchronised PC supported the rhythmic expression of the clock gene Bmal1 in EC in a contact co-culture system, suggesting a secondary form of EC molecular clock regulation. Non-contact co-cultures failed to synchronise EC. Furthermore, when the clock was disrupted in PC, their capacity to support EC's tube-forming capacity on Matrigel was impaired; clock disruption in EC did not affect angiogenesis, supporting the hypothesis that a disrupted clock in perivascular cells affects angiogenesis. In a 3D tissue engineering scaffold seeded with both EC and PC, the synchronisation of the clock led to the development of organised vascular-like structures around the scaffold's pores, as compared to the non-synchronised condition where cells appeared disorganised. Conclusion This study defines for the first time the existence of an endogenous molecular circadian clock in perivascular cells and suggests implications for circadian clock synchronisation in physiological and therapeutic angiogenesis. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Surrey Doctoral CollegeUniversity of Surrey Bioprocess and Biochemical Engineering (BioProChem) Group.

Biomimetic versus sintered macroporous calcium phosphate scaffolds enhanced bone regeneration and human mesenchymal stromal cell engraftment in calvarial defects

In contrast to sintered calcium phosphates (CaPs) commonly employed as scaffolds to deliver mesenchymal stromal cells (MSCs) targeting bone repair, low temperature setting conditions of calcium deficient hydroxyapatite (CDHA) yield biomimetic topology with high specific surface area. In this study, the healing capacity of CDHA administering MSCs to bone defects is evaluated for the first time and compared with sintered beta-tricalcium phosphate (β-TCP) constructs sharing the same interconnected macroporosity. Xeno-free expanded human bone marrow MSCs attached to the surface of the hydrophobic β-TCP constructs, while infiltrating the pores of the hydrophilic CDHA. Implantation of MSCs on CaPs for 8 weeks in calvaria defects of nude mice exhibited complete healing, with bone formation aligned along the periphery of β-TCP, and conversely distributed within the pores of CDHA. Human monocyte-osteoclast differentiation was inhibited in vitro by direct culture on CDHA compared to β-TCP biomaterials and indirectly by administration of MSC-conditioned media generated on CDHA, while MSCs increased osteoclastogenesis in both CaPs in vivo. MSC engraftment was significantly higher in CDHA constructs, and also correlated positively with bone in-growth in scaffolds. These findings demonstrate that biomimetic CDHA are favorable carriers for MSC therapies and should be explored further towards clinical bone regeneration strategies. Statement of significanceDelivery of mesenchymal stromal cells (MSCs) on calcium phosphate (CaP) biomaterials enhances reconstruction of bone defects. Traditional CaPs are produced at high temperature, but calcium deficient hydroxyapatite (CDHA) prepared at room temperature yields a surface structure more similar to native bone mineral. The objective of this study was to compare the capacity of biomimetic CDHA scaffolds with sintered β-TCP scaffolds for bone repair mediated by MSCs for the first time. In vitro, greater cell infiltration occurred in CDHA scaffolds and following 8 weeks in vivo, MSC engraftment was higher in CDHA compared to β-TCP, as was bone in-growth. These findings demonstrate the impact of material features such as surface structure, and highlight that CDHA should be explored towards clinical bone regeneration strategies.

Extrusion-Based 3D Printing of Calcium Magnesium Phosphate Cement Pastes for Degradable Bone Implants.

This study aimed to develop printable calcium magnesium phosphate pastes that harden by immersion in ammonium phosphate solution post-printing. Besides the main mineral compound, biocompatible ceramic, magnesium oxide and hydroxypropylmethylcellulose (HPMC) were the crucial components. Two pastes with different powder to liquid ratios of 1.35 g/mL and 1.93 g/mL were characterized regarding their rheological properties. Here, ageing over the course of 24 h showed an increase in viscosity and extrusion force, which was attributed to structural changes in HPMC as well as the formation of magnesium hydroxide by hydration of MgO. The pastes enabled printing of porous scaffolds with good dimensional stability and enabled a setting reaction to struvite when immersed in ammonium phosphate solution. Mechanical performance under compression was approx. 8–20 MPa as a monolithic structure and 1.6–3.0 MPa for printed macroporous scaffolds, depending on parameters such as powder to liquid ratio, ageing time, strand thickness and distance.

Fabrication of Robust, Shape Recoverable, Macroporous Bacterial Cellulose Scaffolds for Cartilage Tissue Engineering.

Recently, the fabricating of three-dimensional (3D) macroporous bacterial cellulose (MP-BC) scaffolds with mechanically disintegrated BC fragments has attracted considerable attention. However, the successful implementation of these materials depends mainly on their mechanical stability and robustness. Here, a non-toxic crosslinker, 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS), is employed to induce crosslinking reactions between BC fragments. In addition to their large pore sizes, the EDC/NHS-crosslinked MP-BC scaffolds exhibit excellent compression properties and shape recovery ability, owing to the EDC/NHS-induced crosslinking on the BC nanofibers. The results of in vitro studies reveal that the biocompatibility of MP-BC scaffolds is better than that of pristine BC scaffolds because the former provided more space for cell proliferation. The results of in vivo studies show that the neocartilage tissue with native cartilage appearance and abundant cartilage-specific extracellular matrix deposition is successfully regenerated in nude mice. The findings reveal the immense application potential of mechanically robust BC scaffolds with controllable pore sizes and shape-recoverable properties in tissue engineering.

(Pd, Au, Ag) nanoparticles decorated well-ordered macroporous carbon for electrochemical sensing applications

• LS-derived OMC offers large reaction sites and promotes mass and electron transfer. • PDA-based approach proves to be easy, general and efficacious. • OMC loaded noble metal show good sensing activity towards target molecules. The research and develpoment of biomass waste derived carbon materials have attracted tremendous research interests in fabrication of high performance electrochemical sensors. In this work, noble metal NPs (i.e., Pd, Au and Ag) loading on Loofah sponge-derived well-ordered macroporous carbon (OMC)/ N -doped carbon thin layer (N-C) was designed by a general approach. This polydopamine (PDA)-based method has the advantages of simplicity, high efficiency and versatility. In virtue of the synergistic contribution from 3D macroporous carbon scaffold and highly active nobel metal NPs, these as-prepared Pd@OMC/N-C, Au@OMC/N-C and Ag@OMC/N-C electrode exhibit excellent electrochemical sensing performances for H 2 O 2 reduction, glucose oxidation and nitrite oxidation, respectively. Thus, 3D OMC/N-C loaded noble metal nanoparticles are promising materials for a wide spectrum of electrochemical sensor and biosensor applications.

Development of bioinks for 3D printing microporous, sintered calcium phosphate scaffolds

Beta-tricalcium phosphate (β-TCP)-based bioinks were developed to support direct-ink 3D printing-based manufacturing of macroporous scaffolds. Binding of the gelatin:β-TCP ink compositions was optimized by adding carboxymethylcellulose (CMC) to maximize the β-TCP content while maintaining printability. Post-sintering, the gelatin:β-TCP:CMC inks resulted in uniform grain size, uniform shrinkage of the printed structure, and included microporosity within the ceramic. The mechanical properties of the inks improved with increasing β-TCP content. The gelatin:β-TCP:CMC ink (25:75 gelatin:β-TCP and 3% CMC) optimized for mechanical strength was used to 3D print several architectures of macroporous scaffolds by varying the print nozzle tip diameter and pore spacing during the 3D printing process (compressive strength of 13.1 ± 2.51 MPa and elastic modulus of 696 ± 108 MPa was achieved). The sintered, macroporous β-TCP scaffolds demonstrated both high porosity and pore size but retained mechanical strength and stiffness compared to macroporous, calcium phosphate ceramic scaffolds manufactured using alternative methods. The high interconnected porosity (45–60%) and fluid conductance (between 1.04 ×10−9 and 2.27 × 10−9 m4s/kg) of the β-TCP scaffolds tested, and the ability to finely tune the architecture using 3D printing, resulted in the development of novel bioink formulations and made available a versatile manufacturing process with broad applicability in producing substrates suitable for biomedical applications.

Biomechanical performances of PCL/HA micro- and macro-porous lattice scaffolds fabricated via laser powder bed fusion for bone tissue engineering

The present experimental study aims to extend know-how on resorbable polycaprolactone/hydroxyapatite (PCL/HA, 70/30 wt%) scaffolds, produced by Laser Powder Bed Fusion (LPBF) technology, to geometrically complex lattice structures and micro porous struts. Using optimized LPBF printing parameters, micro- and macro-porous scaffolds for bone tissue regeneration were produced by regularly repeating in space Diamond (DO) and Rhombic Dodecahedron (RD) elementary unit cells. After production, scaffolds were submitted to structural, mechanical, and biological characterization. The interaction of scaffolds with human Mesenchymal Stem Cells (hMSCs) allowed studying the degradative processes of the PCL matrix. Biomechanical performances and biodegradation of scaffolds were compared to literature results and bone tissue data. Mechanical compression test, biological viability up to 4 days of incubation and degradation rate evidenced strong dependence of scaffold behavior on unit cell geometry as well as on global geometrical features.

Evaluation of natural gum-based cryogels for soft tissue engineering

In this study, three natural biomaterials, Locust bean gum (LBG), Xanthan gum (XG), and Mastic gum (MG), were combined to form cryogel scaffolds. Thermal and chemical characterizations revealed the successful blend formation from LBG-XG (LX) and LBG-XG-MG (LXM) polymers. All blends resulted in macro-porous scaffolds with interconnected pore structures under the size of 400 μm. The swollen cryogels had similar mechanical properties compared with other polysaccharide-based cryogels. The mean tensile and compressive modulus values of the wet cryogels were in the range of 3.5–11.6 kPa and 82–398 kPa, respectively. The sustained release of the small molecule Kartogenin from varying concentrations and ratios of cryogels was in between 32 and 66% through 21 days of incubation. Physical, mechanical, and chemical properties make LX and LXM polysaccharide-based cryogels promising candidates for cartilage and other soft tissue engineering, and drug delivery applications.

UV curing–assisted 3D plotting of core-shelled feedrod for macroporous hydroxyapatite scaffolds comprised of microporous hollow filaments

The present study demonstrates the manufacturing of macroporous hydroxyapatite (HA) scaffolds, comprised of microporous hollow filaments with high shape retention, by UV curing-assisted 3D plotting using a feedrod comprised of a photocurable HA shell and a carbon black (CB) core. Two types of scaffolds with different filament interspaces (0.5 mm and 1 mm) were produced by depositing core-shelled filaments extruded through a 1.07-mm-diameter nozzle with in situ polymerization process. Both scaffolds exhibited that the hollow HA filaments were produced after the removal of CB core by heat-treatment, while micropores in the HA walls were created as the replica of camphene-camphor crystals. Overall porosity and macroporosity obtained using a camphene-camphor content of 60 vol% increased from 74.3 vol% to 79.3 vol% and from 50.7 vol% and 64.6 vol%, respectively, with an increase in filament interspace sizes from 0.5 mm to 1 mm. Both scaffolds exhibited reasonably high compressive strengths (2.36 ― 3.58 MPa) and modulus (68–86 MPa).

Preparation and characterization of a 3-dimensional macroporous bacterial cellulose scaffold for in vitro tissue engineering applications

The increasing need for a new tissue engineering scaffold has revived interest in bacterial cellulose (BC) and its water holding capacity (WHC), porosity, and biocompatibility. Bacterial cellulose was produced using Gluconacetobacter xylinus, and bacterial cellulose film (BCF) was prepared by lyophilization. To obtain macroporous bacterial cellulose (MBCS), BCF was rinsed with poly(ethylene glycol) (PEG-400), adjusted to 0.25% BC concentration, and freeze-dried. The objective of this study to compare BCF and MBCS in terms of porosity, in vitro degradation, WHC, and the cell viability of mouse fibroblast cell line (NIH-3T3). The results showed that the MBCS has great potential for tissue engineering.