Extrusion 3D printing of a multiphase collagen-based material: An optimized strategy to obtain biomimetic scaffolds with high shape fidelity

Extrusion printing represents one of the leading additive manufacturing techniques for tissue engineering purposes due to the possibility of achieving accurate control of the final shape and porosity of the scaffold. Despite many polymeric materials having already been optimized for this application, the processing of biopolymer-based systems still presents several limitations mainly ascribed to their poor rheological properties. Moreover, the introduction of inorganic components into the biomaterial formulation may introduce further difficulties related to system homogeneity, finally compromising its extrudability. In this context, the present study aimed at developing a new multi-phase biomaterial ink able to mimic the native composition of bone extracellular matrix, combining type-I-collagen with nano-hydroxyapatite and mesoporous bioactive glass nanoparticles. Starting from a comprehensive rheological assessment, computational-fluid-dynamics-based models were exploited to describe the material flow regime and define the optimal printing process planning. During printing, a gelatin-based bath was exploited to support the deposition of the material, while the gelation of collagen and its further chemical crosslinking with genipin enabled the stabilization of the printed structure, characterized by high shape fidelity. The developed strategy enables the extrusion printing of complex multi-phase systems and the design of high-precision biomimetic scaffolds with great potential for bone tissue engineering

Bioceramics and scaffolds: a winning combination for tissue engineering

In the last few decades we have assisted to a general increase of elder population worldwide with associated age-related pathologies. Therefore, there is the need for new biomaterials that can substitute damaged tissues, stimulate the body’s own regenerative mechanisms and promote tissue healing. Porous templates referred to as scaffolds are thought to be required for three-dimensional tissue growth. Bioceramics, a special set of fully, partially or non-crystalline ceramics (e.g. calcium phosphates, bioactive glasses and glass-ceramics) that are designed for the repair and reconstruction of diseased parts of the body, have high potential as scaffold materials. Traditionally, bioceramics have been used to fill and restore bone and dental defects (repair of hard tissues). More recently, this category of biomaterials has also revealed promising applications in the field of soft tissue engineering. Starting with an overview of the fundamental requirements for tissue engineering scaffolds, this article provides a detailed picture on recent developments of porous bioceramics and composites, including a summary of common fabrication technologies and a critical analysis of structure-property and structure-function relationships. Areas of future research are highlighted at the end of this review, with special attention to the development of multifunctional scaffolds exploiting therapeutic ion/drug release and emerging applications beyond hard tissue repair

Collagen and non-collagenous proteins molecular crosstalk in the pathophysiology of osteoporosis.

Abstract Collagenous and non-collagenous proteins (NCPs) in the extracellular matrix, as well as the coupling mechanisms between osteoclasts and osteoblasts, work together to ensure normal bone metabolism. Each protein plays one or more critical roles in bone metabolism, sometimes even contradictory, thus affecting the final mechanical, physical and chemical properties of bone tissue. Anomalies in the amount and structure of one or more of these proteins can cause abnormalities in bone formation and resorption, which consequently leads to malformations and defects, such as osteoporosis (OP). The connections between key proteins involved in matrix formation and resorption are far from being elucidated. In this review, we resume knowledge on the crosstalk between collagen type I and selected NCPs (Transforming Growth Factor-β, Insulin-like Growth Factor-1, Decorin, Osteonectin, Osteopontin, Bone Sialoprotein and Osteocalcin) of bone matrix, focusing on their possible involvement and role in OP. The different elements of this network can be pharmacologically targeted or used for the design/development of innovative regenerative strategies to modulate a feedback loop in bone remodelling

Composite biomaterials based on sol-gel mesoporous silicate glasses: a review

Bioactive glasses are able to bond to bone and stimulate the growth of new tissue while dissolving over time, which makes them ideal materials for regenerative medicine. The advent of mesoporous glasses, which are typically synthesized via sol-gel routes, allowed researchers to develop a broad and versatile class of novel biomaterials that combine superior bone regenerative potential (compared to traditional melt-derived glasses) with the ability of incorporating drugs and various biomolecules for targeted therapy in situ. Mesoporous glass particles can be directly embedded as a bioactive phase within a non-porous (e.g., microspheres), porous (3D scaffolds) or injectable matrix, or be processed to manufacture a surface coating on inorganic or organic (macro)porous substrates, thereby obtaining hierarchical structures with multiscale porosity. This review provides a picture of composite systems and coatings based on mesoporous glasses and highlights the challenges for the future, including the great potential of inorganic–organic hybrid sol-gel biomaterials

Strontium Functionalization of Biomaterials for Bone Tissue Engineering Purposes: A Biological Point of View

Strontium (Sr) is a trace element taken with nutrition and found in bone in close connection to native hydroxyapatite. Sr is involved in a dual mechanism of coupling the stimulation of bone formation with the inhibition of bone resorption, as reported in the literature. Interest in studying Sr has increased in the last decades due to the development of strontium ranelate (SrRan), an orally active agent acting as an anti-osteoporosis drug. However, the use of SrRan was subjected to some limitations starting from 2014 due to its negative side effects on the cardiac safety of patients. In this scenario, an interesting perspective for the administration of Sr is the introduction of Sr ions in biomaterials for bone tissue engineering (BTE) applications. This strategy has attracted attention thanks to its positive effects on bone formation, alongside the reduction of osteoclast activity, proven by in vitro and in vivo studies. The purpose of this review is to go through the classes of biomaterials most commonly used in BTE and functionalized with Sr, i.e., calcium phosphate ceramics, bioactive glasses, metal-based materials, and polymers. The works discussed in this review were selected as representative for each type of the above-mentioned categories, and the biological evaluation in vitro and/or in vivo was the main criterion for selection. The encouraging results collected from the in vitro and in vivo biological evaluations are outlined to highlight the potential applications of materials' functionalization with Sr as an osteopromoting dopant in BTE

Novel multifunctional strontium-copper co-substituted mesoporous bioactive particles

Abstract Sr-Cu co-substituted mesoporous bioactive glasses were synthesized by two different sol-gel approaches: an ultrasound-assisted base-catalyzed sol-gel procedure and an aerosol-assisted spray-drying method. The produced spherical shaped particles showed high specific surface area values and tunable pore size. The two different routes allowed obtaining samples with different morphology and size, characterized by the ability to induce hydroxyapatite deposition, to incorporate a specific amount of therapeutic ions (strontium with the aim to improve bone formation and copper for its antibacterial and pro-angiogenic properties) and to release them. The obtained multifunctional biomaterials synergistically combine the ability to promote bone formation and angiogenesis and to impart an antibacterial effect

Type I Collagen and Strontium-Containing Mesoporous Glass Particles as Hybrid Material for 3D Printing of Bone-Like Materials

Bone tissue engineering offers an alternative promising solution to treat a large number of bone injuries with special focus on pathological conditions, such as osteoporosis. In this scenario, the bone tissue regeneration may be promoted using bioactive and biomimetic materials able to direct cell response, while the desired scaffold architecture can be tailored by means of 3D printing technologies. In this context, our study aimed to develop a hybrid bioactive material suitable for 3D printing of scaffolds mimicking the natural composition and structure of healthy bone. Type I collagen and strontium-containing mesoporous bioactive glasses were combined to obtain suspensions able to perform a sol-gel transition under physiological conditions. Field emission scanning electron microscopy (FESEM) analyses confirmed the formation of fibrous nanostructures homogeneously embedding inorganic particles, whereas bioactivity studies demonstrated the large calcium phosphate deposition. The high-water content promoted the strontium ion release from the embedded glass particles, potentially enhancing the osteogenic behaviour of the composite. Furthermore, the suspension printability was assessed by means of rheological studies and preliminary extrusion tests, showing shear thinning and fast material recovery upon deposition. In conclusion, the reported results suggest that promising hybrid systems suitable for 3D printing of bioactive scaffolds for bone tissue engineering have been developed