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Human mesenchymal stromal cells (hMSCs), whether used alone or together with three-dimensional scaffolds, are the best-studied postnatal stem cells in regenerative medicine. In this study, innovative composite scaffolds consisting of a core–shell architecture were seeded with bone-marrow-derived hMSCs (BM-hMSCs) and tested for their biocompatibility and remarkable capacity to promote and support bone regeneration and mineralization. The scaffolds were prepared by grafting three different amounts of gelatin–chitosan (CH) hydrogel into a 3D-printed polylactic acid (PLA) core (PLA-CH), and the mechanical and degradation properties were analyzed. The BM-hMSCs were cultured in the scaffolds with the presence of growth medium (GM) or osteogenic medium (OM) with differentiation stimuli in combination with fetal bovine serum (FBS) or human platelet lysate (hPL). The primary objective was to determine the viability, proliferation, morphology, and spreading capacity of BM-hMSCs within the scaffolds, thereby confirming their biocompatibility. Secondly, the BM-hMSCs were shown to differentiate into osteoblasts and to facilitate scaffold mineralization. This was evinced by a positive Von Kossa result, the modulation of differentiation markers (osteocalcin and osteopontin), an expression of a marker of extracellular matrix remodeling (bone morphogenetic protein-2), and collagen I. The results of the energy-dispersive X-ray analysis (EDS) clearly demonstrate the presence of calcium and phosphorus in the samples that were incubated in OM, in the presence of FBS and hPL, but not in GM. The chemical distribution maps of calcium and phosphorus indicate that these elements are co-localized in the same areas of the sections, demonstrating the formation of hydroxyapatite. In conclusion, our findings show that the combination of BM-hMSCs and PLA-CH, regardless of the amount of hydrogel content, in the presence of differentiation stimuli, can provide a construct with enhanced osteogenicity for clinically relevant bone regeneration. [ABSTRACT FROM AUTHOR]

Motivated by the enormous potential of hydrogels in regenerative medicine, new biocompatible gelatin-based hybrid hydrogels were developed through a green process using poly(ethylene glycol) diglycidyl ether as a cross-linking agent, adding carrageenan and chitosan polysaccharides to the network to better mimic the hybrid composition of native extracellular matrix. Overall, the hydrogels show suitable structural stability, high porosity and pore interconnectivity, good swellability, and finally, biocompatibility. Their mechanical behavior, investigated by tensile and compression tests, appears to be characterized by nonlinear elasticity with high compliance values, fast stress-relaxation, and good strain reversibility with no sign of mechanical failure for compressive loading–unloading cycles at relatively high deformation levels of 50%. Degradation tests confirm the hydrogel bioresorbability by gradual hydrolysis, during which the structural integrity of both materials is maintained, while their mechanical behavior becomes more and more compliant. Human Umbilical Cord-derived Mesenchymal Stem Cells (hUC-MSCs) were used to test the hydrogels as potential carriers for cell delivery in tissue engineering. hUC-MSCs cultured inside the hydrogels show a homogenous distribution and maintain their growth and viability for at least 21 days of culture, with an increasing proliferation trend. Hence, this study contributes to a further understanding of the potential use of hybrid hydrogels and hUC-MSCs for a wide range of biomedical applications, particularly in soft tissue engineering. [ABSTRACT FROM AUTHOR]

Hydrogels are attracting ample attention for tissue engineering application thanks to their water-loving attribute and closely mimicry to the natural extracellular matrix. However, effectively and efficiently sterilization of hydrogels without compromising their end-use beneficial attributes is a major challenge. The aim of this work is to study the resistance to gamma sterilization of newly developed gelatin-based hybrid hydrogels for tissue engineering. This study reported the investigation of 25 kGy gamma sterilization, a typical sterilization procedure for healthcare products, on the physicomechanical and thermal properties of a three set of gelatin-based novel hydrogels, namely, gelatin-polyethylene glycol (G/PEG), G-PEG-hydroxyethyl cellulose (G/PEG/HEC), and G-PEG-chitosan (G/PEG/CH). Fourier transform infrared and thermogravimetric analysis were done to evaluate the chemical change and variation of thermal behavior, respectively, imposed by the gamma exposure, and the results showed that gamma sterilization did not modify the chemical composition and thermal degradation behavior of the hydrogels. The water uptake, mechanical properties (both in tension and compression), and stress relaxation experiments revealed that parent G/PEG and interpenetrating polymer network (IPN) G/PEG/CH were nearly negligibly sensitive to the gamma sterilization. However, semi-IPN G/PEG/HEC appeared to be slightly vulnerable to the gamma exposure: a decrease in modulus and strength but simultaneous increase in water uptake, percentage dissipation energy, and stress relaxation responses were observed., INTRODUCTION Hydrogels, a water-rich polymeric cross-linked network, have emerged as the most potential scaffolding substrate for three-dimensional (3D) cell culture in tissue engineering. They excel over other scaffolding materials owing [...]

Scaffolds for tissue engineering are expected to respond to a challenging combination of physical and mechanical requirements, guiding the research towards the development of novel hybrid materials. This study introduces innovative three-dimensional bioresorbable scaffolds, in which a stiff poly(lactic acid) lattice structure is meant to ensure temporary mechanical support, while a bioactive gelatin–chitosan hydrogel is incorporated to provide a better environment for cell adhesion and proliferation. The scaffolds present a core–shell structure, in which the lattice core is realized by additive manufacturing, while the shell is nested throughout the core by grafting and crosslinking a hydrogel forming solution. After subsequent freeze-drying, the hydrogel network forms a highly interconnected porous structure that completely envelops the poly(lactic acid) core. Thanks to this strategy, it is easy to tailor the scaffold properties for a specific target application by properly designing the lattice geometry and the core/shell ratio, which are found to significantly affect the scaffold mechanical performance and its bioresorption. Scaffolds with a higher core/shell ratio exhibit higher mechanical properties, whereas reducing the core/shell ratio results in higher values of bioactive hydrogel content. Hydrogel contents up to 25 wt% could be achieved while maintaining high compression stiffness (>200 MPa) and strength (>5 MPa), overall, within the range of values displayed by human bone tissue. In addition, mechanical properties remain stable after prolonged immersion in water at body temperature for several weeks. On the other hand, the hydrogel undergoes gradual and homogeneous degradation over time, but the core–shell integrity and structural stability are nevertheless maintained during at least 7-week hydrolytic degradation tests. In vitro experiments with human mesenchymal stromal cells reveal that the core–shell scaffolds are biocompatible, and their physical–mechanical properties and architecture are suitable to support cell growth and osteogenic differentiation, as demonstrated by hydroxyapatite formation. These results suggest that the bioresorbable core–shell scaffolds can be considered and further studied, in view of clinically relevant endpoints in bone regenerative medicine. [ABSTRACT FROM AUTHOR]

Conductive nanocomposites play a significant role in tissue engineering by providing a platform to support cell growth, tissue regeneration, and electrical stimulation. In the present study, a set of electroconductive nanocomposite hydrogels based on gelatin (G), chitosan (CH), and conductive carbon black (CB) was synthesized with the aim of developing novel biomaterials for tissue regeneration application. The incorporation of conductive carbon black (10, 15 and 20 wt.%) significantly improved electrical conductivity and enhanced mechanical properties with the increased CB content. We employed an oversimplified unidirectional freezing technique to impart anisotropic morphology with interconnected porous architecture. An investigation into whether any anisotropic morphology affects the mechanical properties of hydrogel was conducted by performing compression and cyclic compression tests in each direction parallel and perpendicular to macroporous channels. Interestingly, the nanocomposite with 10% CB produced both anisotropic morphology and mechanical properties, whereas anisotropic pore morphology diminished at higher CB concentrations (15 and 20%), imparting a denser texture. Collectively, the nanocomposite hydrogels showed great structural stability as well as good mechanical stability and reversibility. Under repeated compressive cyclic at 50% deformation, the nanocomposite hydrogels showed preconditioning, characteristic hysteresis, nonlinear elasticity, and toughness. Overall, the collective mechanical behavior resembled the mechanics of soft tissues. The electrical impedance associated with the hydrogels was studied in terms of the magnitude and phase angle in dry and wet conditions. The electrical properties of the nanocomposite hydrogels conducted in wet conditions, which is more physiologically relevant, showed a decreasing magnitude with increased CB concentrations, with a resistive-like behavior in the range 1 kHz–1 MHz and a capacitive-like behavior for frequencies <1 kHz and >1 MHz. Overall, the impedance of the nanocomposite hydrogels decreased with increased CB concentrations. Together, these nanocomposite hydrogels are compositionally, morphologically, mechanically, and electrically similar to native ECMs of many tissues. These gelatin-chitosan–carbon black nanocomposite hydrogels show great promise for use as conducting substrates for the growth of electro-responsive cells in tissue engineering. [ABSTRACT FROM AUTHOR]

In this work hydroxyethylcellulose (HEC) was employed to prepare macroporous polyacrylamide (PAAm) hydrogels with different porosities and degrees of interconnectivity. The porosity and the equilibrium mass swelling ratio of hydrogels equilibrated in 0.1 M NaCI increased with the amount of HEC employed in the reaction mixture. Tensile and fracture tests were performed to investigate the mechanical behavior of both as prepared hydrogels and of hydrogels equilibrated in 0.1 M NaCI. As prepared hydrogels displayed invariably better mechanical properties than the corresponding equilibrated hydrogels. The mechanical stiffness decreased regularly as the amount of HEC (and porosity) was increased. A more complex trend was observed for the ultimate properties (elongation and stress at break) and for the fracture resistance, which displayed a maximum at intermediate HEC contents., INTRODUCTION According to IUPAC macroporous polymers contain a large number of macropores (50 nm to 1 pm in diameter), while pore diameters are less than 2 nm in microporous polymers [...]

A series of amine-hardened epoxies were prepared by systematically varying the stoichiometric ratio and the relative amounts of diepoxide and monoepoxide resin to chemically control the material composition and macromolecular architecture (chain segments flexibility; crosslink density; amounts of dangling groups). Positron Annihilation Lifetime Spectroscopy was used to investigate the free volume associated to the various epoxy formulations, while dynamic-mechanical analysis was employed to investigate their network density and their primary and secondary mechanical relaxations. The mechanical behavior at small and large strain was studied by means of tensile and compression tests. The results pointed out that deviations from the ideal stoichiometric composition and the addition of monoepoxide resins lead to significant room temperature stiffening, together with a reduction of the crosslink density and glass transition temperature. This behavior, phenomenologically associated to antiplasticization, was interpreted according to the specific macromolecular architecture and ascribed to chain mobility hindrance, as revealed by secondary transitions, whereas no significant contribution from the free volume could be evidenced. Furthermore, it was shown that depending on the strain scale and on the corresponding deformational mechanisms, the mechanical response may be differently influenced either by the presence of dangling groups or by the network density., INTRODUCTION Epoxy resins are a large class of thermosetting polymers that encounter large interest in various technological applications (e.g., adhesives, coatings and high-performance composites) thanks to their thermomechanical and chemical [...]

The mechanical properties of scaffolds play a vital role in regulating key cellular processes in tissue development and regeneration in the field of tissue engineering. Recently, scaffolding material design strategies leverage viscoelasticity to guide stem cells toward specific tissue regeneration. Herein, we designed and developed a viscoelastic Gel-PEG hybrid hydrogel with anisotropic morphology and mechanical properties using a gelatin and functionalized PEG (as a crosslinker) under a benign condition for tissue engineering application. The chemical crosslinking/grafting reaction was mainly involved between epoxide groups of PEG and available functional groups of gelatin. FTIR spectra revealed the hybrid nature of Gel-PEG hydrogel. The hybrid hydrogel showed good swelling behavior (water content > 600%), high porosity and pore interconnectivity suitable for tissue engineering application. Simple unidirectional freezing followed by a freeze-drying technique allowed the creation of structurally stable 3D anisotropic macroporous architecture that showed tissue-like elasticity and was capable of withstanding high deformation (50% strain) without being damaged. The tensile and compressive modulus of Gel-PEG hybrid hydrogel were found to be 0.863 MPa and 0.330 MPa, respectively, which are within the range of normal human articular cartilage. In-depth mechanical characterizations showed that the Gel-PEG hybrid hydrogel possessed natural-tissue-like mechanics such as non-linear and J-shaped stress-strain curves, stress softening effect, high fatigue resistance and stress relaxation response. A month-long hydrolytic degradation test revealed that the hydrogel gradually degraded in a homogeneous manner over time but maintained its structural stability and anisotropic mechanics. Overall, all these interesting features provide a potential opportunity for Gel-PEG hybrid hydrogel as a scaffold in a wide range of tissue engineering applications. [ABSTRACT FROM AUTHOR]

Bone regenerative medicine is a clinical approach combining live osteoblast progenitors, such as mesenchymal stromal cells (MSCs), with a biocompatible scaffold that can integrate into host bone tissue and restore its structural integrity. Over the last few years, many tissue engineering strategies have been developed and thoroughly investigated; however, limited approaches have been translated to clinical application. Consequently, the development and clinical validation of regenerative approaches remain a centerpiece of investigational efforts towards the clinical translation of advanced bioengineered scaffolds. The aim of this review was to identify the latest clinical trials related to the use of scaffolds with or without MSCs to regenerate bone defects. A revision of the literature was performed in PubMed, Embase, and Clinicaltrials.gov from 2018 up to 2023. Nine clinical trials were analyzed according to the inclusion criteria: six presented in the literature and three reported in Clinicaltrials.gov. Data were extracted covering background trial information. Six of the clinical trials added cells to scaffolds, while three used scaffolds alone. The majority of scaffolds were composed of calcium phosphate ceramic alone, such as β-tricalcium phosphate (TCP) (two clinical trials), biphasic calcium phosphate bioceramic granules (three clinical trials), and anorganic bovine bone (two clinical trials), while bone marrow was the primary source of the MSCs (five clinical trials). The MSC expansion was performed in GMP facilities, using human platelet lysate (PL) as a supplement without osteogenic factors. Only one trial reported minor adverse events. Overall, these findings highlight the importance and efficacy of cell–scaffold constructs in regenerative medicine under different conditions. Despite the encouraging clinical results obtained, further studies are needed to assess their clinical efficacy in treating bone diseases to optimize their application. [ABSTRACT FROM AUTHOR]

Bisphenol-A polycarbonate (PC)/poly(methyl methacrylate) (PMMA) blends (PC/PMMA) were prepared by melt mixing with and without a trans-esterification catalyst (tetrabutylammoniun tetraphenylborate), which is able to promote inter-exchange reactions between PC and PMMA. Evidences of the ester-ester exchange reaction taking place were pointed out via Fourier Transform Infra-Red and size exclusion chromatography analyses. A series of enthalpy relaxation measurements were carried out for the pure polymers and for blends thereof. The data were analyzed on the basis of the Tool-Narayanaswamy-Moynihan/Kohlraush-Williams-Watts model. This model characterizes the structural relaxation in the glass transition region by means of four parameters: the apparent activation energy (Δh*), the nonlinearity (x), the nonexponentiality (β), and the pre-exponential factor ([τ.sub.0]). The apparent activation energy can be determined from the cooling rate dependence of the fictive temperature ([T.sub.f]) measured using DSC. Δh* values of homogeneous blend and of the starting polymers were determined in this way, while an estimation of x, β and [τ.sub.0] was proposed. Comparisons were made between a single glass transition temperature PC/PMMA blend and homopolymers data. The experimental values of Δh* suggest that the degree of cooperativity decreases on going from the starting polymers to the blend. POLYM. ENG. SCI., 47:218-224, 2007. © 2007 Society of Plastics Engineers, INTRODUCTION Among a number of studies on poly(methyl methacrylate) (PMMA) blends the mixture PMMA and of bisphenol-A polycarbonate (PC) is one of the most deeply studied polymers pair. This may [...]

A great promise for tissue engineering is represented by scaffolds that host stem cells during proliferation and differentiation and simultaneously replace damaged tissue while maintaining the main vital functions. In this paper, a novel process was adopted to develop composite scaffolds with a core-shell structure for bone tissue regeneration, in which the core has the main function of temporary mechanical support, and the shell enhances biocompatibility and provides bioactive properties. An interconnected porous core was safely obtained, avoiding solvents or other chemical issues, by blending poly(lactic acid), poly(ε-caprolactone) and leachable superabsorbent polymer particles. After particle leaching in water, the core was grafted with a gelatin/chitosan hydrogel shell to create a cell-friendly bioactive environment within its pores. The physicochemical, morphological, and mechanical characterization of the hybrid structure and of its component materials was carried out by means of infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and mechanical testing under different loading conditions. These hybrid polymer devices were found to closely mimic both the morphology and the stiffness of bones. In addition, in vitro studies showed that the core-shell scaffolds are efficiently seeded by human mesenchymal stromal cells, which remain viable, proliferate, and are capable of differentiating towards the osteogenic phenotype if adequately stimulated. [ABSTRACT FROM AUTHOR]

High performance gelatin-based biocompatible hybrid hydrogels are developed using functionalized polyethylene glycol as a cross-linker in presence of chitosan or hydroxyethyl cellulose. Tensile test shows robust and tunable mechanical properties and reveals non-linear and J-shaped stress-strain curves similar to those found for native extracellular matrix. Degradation study demonstrates that the mass loss and change in mechanical properties are dependent on hydrogel composition and cross-linking density. Structural features of the hydrogels are confirmed by infrared spectroscopy. A preliminary biological evaluation is carried out using rat myoblasts and human fibroblasts cell lines. The results show that all hydrogels allow cell adhesion and proliferation during four days culture, hence, they might have a great potential for use in the biomedical applications. [ABSTRACT FROM AUTHOR]

In this research work, novel hybrid materials based on multifunctional polymers and silica were developed and investigated in view of possible employment as sorbents for removal of heavy metal ions from water in presence of various ions. Organic-inorganic hybrid materials were prepared by covalent bonding of vinyl-terminated polyamidoamine (PAA) onto aminated silica particles. Two series of polyamidoamine-grafted silica, differing in the PAA chemical structure, were synthesized, and their heavy metal ions chelating properties were investigated. Column adsorption procedure for Cu, Zn, and Ni in aqueous solution was successfully established. Moreover, the adsorption behaviour of the materials was evaluated in different ionic strength solutions as well as in distilled and natural water. Organic-inorganic hybrid materials exhibited excellent chelating properties and selectivity for different metal ions. The hybrid columns showed exceptional eluting and regenerating property using diluted hydrochloric acid solution as eluent. In particular, the hybrid materials containing more carboxy groups possessed superior adsorption ability, reusability, and stability. The consecutive adsorption-desorption experiments exhibited that this material could be reused more than 20 cycles without almost any loss of adsorption capability. These new organic-inorganic sorbents appear very promising as an effective solid-phase extraction material for the selective preconcentration or removing of heavy metal ions from the environment. [ABSTRACT FROM AUTHOR]

Novel biodegradable polymeric materials based on protein hydrolysate (Pr.Hyd), derived from waste products of the leather industry, and poly(ethylene glycol) diglycidyl ether (PEG) or epoxidized soybean oil (ESO) are obtained and their physico‐chemical properties and mechanical behaviour are evaluated. Different processing conditions and the introduction of fillers of natural origin, as saw dust and wood flour, are used to tailor the mechanical properties and the environmental durability of the product. The biodegradable products, which are almost completely manufactured from renewable‐based raw materials, look promising for several applications, particularly in agriculture for the additional fertilizing action of Pr.Hyd. To this purpose, tests are carried out to prove the feasibility of novel biodegradable pots and containers by investigating their functionality, their physico‐chemical and mechanical behaviour in standard and controlled experimental field conditions, and to follow the assessment of their biodegradation process during plants cultivation in the soil. POLYM. COMPOS., 39:2743–2750, 2018. © 2016 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

ABSTRACT In this research work, biocomposites based on crosslinked particles of sodium polyacrylate, commonly used as superabsorbent polymer, and poly( l-lactic acid) (PLLA) were developed to obtain superabsorbent thermoplastic products, and to elucidate the role of this type of filler (i.e., polymeric crosslinked particles) on their overall physical-mechanical behavior. Samples prepared by melt-blending components with different ratios showed a biphasic system with a uniform distribution of particles, with diameters up to about 50 μm, within the PLLA polymeric matrix. The polymeric biphasic system, coded PLASA, that is, superabsorbent PLLA, showed excellent swelling properties, demonstrating that crosslinked particles retain their superabsorbent ability even if distributed in a thermoplastic polymeric matrix. The thermal characteristics of the biocomposites evidenced enhanced thermal stability in comparison with neat PLLA and also mechanical properties are markedly modified by addition of crosslinked particles, revealing a regular stiffening effect. Furthermore, in aqueous environments the particles swell and are leached from PLLA matrix generating very high porosity. These new open-pore foams coded PLASAW, that is, PLASA after water treatment, produced in absence of organic solvents and chemical foaming agents, with good physicomechanical properties appear very promising for several applications, for instance in tissue engineering for scaffold production. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45655. [ABSTRACT FROM AUTHOR]

The article focuses on evaluating an innovative three-dimensional bioresorbable scaffold made of gelatin-chitosan hydrogel with a stiff poly(lactic acid) lattice structure for bone regeneration and its ability to support the differentiation of seeded BM-hMSCs into osteogenic lineages.

Blends based on protein hydrolysate (PH), derived from waste products of the leather industry, and poly(ethylene- co-vinyl acetate) (EVA), were obtained by reactive blending and their physico-chemical properties as well as their mechanical and rheological behavior were evaluated. The effect of vinyl acetate content and of a transesterification agent added to increase interaction between polymer and bio-based components were investigated. Novel biodegradable polymeric materials for spray mulching coatings were also obtained from hydrolyzed proteins and end-functionalized poly(ethylene glycol) (PEG), which was used as crosslinking agent. These products, almost entirely obtained from renewable sources, represent a new type of biodegradable material which looks promising for several applications, for instance in packaging or in agriculture as transplanting or mulching films with additional fertilizing action of PH. POLYM. COMPOS., 37:3416-3422, 2016. © 2015 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Polymeric blends based on ethylene vinyl acetate (EVA) rubbers filled with high molecular weight carboxymethyl cellulose were investigated in view of possible employment as biodegradable materials. The effect of vinyl acetate (VA) content and of addition of transesterification agent to increase interaction between EVA and cellulosic components was considered. Blends reinforced with cellulose microfibers in different amounts were also characterized in their mechanical, rheological, and thermal behavior. POLYM. COMPOS., 36:980-986, 2015. © 2015 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

This article presents a study regarding enthalpy relaxation in Bisphenol-A polycarbonate/poly(methyl methacrylate) blends. It aims to study the enthalpy relaxation in single glass transition temperature PC/PMMA blend gained by reactive mixing. Moreover, it also performed a comparison with pure components.

In this work the compatibility of aromatic copolycarbonates containing bisphenol A (BPA) and tetramethyl bisphenol A (TMBPA) with polystyrene (PS) was investigated. Miscibility prediction data were used to select copolycarbonates of potential interest for developing highly compatible blends. Statistical copolycarbonates (CPCs) containing different BPA/TMBPA molar ratios were synthesized by polycondensation reaction and the effect of copolymer composition on the PS/CPC miscibility was studied. The blends were prepared by casting from chloroform solutions and/or melt mixing. The compatibility was evaluated by optical microscopy (OM), calorimetric (DSC), and dynamic-mechanical thermal (DMTA) analyses. Two glass transition temperatures were found for all the prepared PS/CPC blends, but an improvement of compatibility was obtained increasing TMBPA content in CPC copolymer. On the other hand, blends of polycarbonate of bisphenol A (PCPA) and CPCs were characterized by a single glass transition temperature and transesterification reaction was noticed. Finally, a compatibilization effect of CPCs and polycarbonate of tetramethyl-bisphenol A (PCTMP) was highlighted in PS/PCPA/CPCs and PS/PCPA/PCTMP three components blends. [ABSTRACT FROM AUTHOR]

Gelatin–dextran hydrogel scaffolds (G-PEG-Dx) were evaluated for their ability to activate the bone marrow human mesenchymal stromal cells (BM-hMSCs) towards mineralization. G-PEG-Dx1 and G-PEG-Dx2, with identical composition but different architecture, were seeded with BM-hMSCs in presence of fetal bovine serum or human platelet lysate (hPL) with or without osteogenic medium. G-PEG-Dx1, characterized by a lower degree of crosslinking and larger pores, was able to induce a better cell colonization than G-PEG-Dx2. At day 28, G-PEG-Dx2, with hPL and osteogenic factors, was more efficient than G-PEG-Dx1 in inducing mineralization. Scanning electron microscopy (SEM) and Raman spectroscopy showed that extracellular matrix produced by BM-hMSCs and calcium-positive mineralization were present along the backbone of the G-PEG-Dx2, even though it was colonized to a lesser degree by hMSCs than G-PEG-Dx1. These findings were confirmed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), detecting distinct lipidomic signatures that were associated with the different degree of scaffold mineralization. Our data show that the architecture and morphology of G-PEG-Dx2 is determinant and better than that of G-PEG-Dx1 in promoting a faster mineralization, suggesting a more favorable and active role for improving bone repair. [ABSTRACT FROM AUTHOR]