The induction of bone formation by 3D-printed PLGA microsphere scaffolds in a calvarial orthotopic mouse model: a pilot study.

Polymeric biodegradable microspheres are readily utilized to support targeted drug delivery for various diseases clinically. 3D printed tissue engineering scaffolds from polymer filaments with embedded microspheres or nanoparticles, as well as bulk microsphere scaffolds, have been investigated for regenerative medicine and tissue engineering. However, 3D printed scaffolds consisting only of a homogenous microsphere size with an optimized architecture that includes a unique micro- and macroporosity, have been challenging to produce and hence, have not been assessed in the literature yet.

The 3D-McMap Guidelines: Three-Dimensional Multicomposite Microsphere Adaptive Printing.

Microspheres, synthesized from diverse natural or synthetic polymers, are readily utilized in biomedical tissue engineering to improve the healing of various tissues. Their ability to encapsulate growth factors, therapeutics, and natural biomolecules, which can aid tissue regeneration, makes microspheres invaluable for future clinical therapies. While microsphere-supplemented scaffolds have been investigated, a pure microsphere scaffold with an optimized architecture has been challenging to create via 3D printing methods due to issues that prevent consistent deposition of microsphere-based materials and their ability to maintain the shape of the 3D-printed structure.

Enhancement of properties of a cell-laden GelMA hydrogel-based bioink via calcium phosphate phase transition.

To improve the properties of the hydrogel-based bioinks, a calcium phosphate phase transition was applied, and the products were examined. We successfully enhanced the mechanical properties of the hydrogels by adding small amounts (< 0.5 wt%) of alpha-tricalcium phosphate (-TCP) to photo-crosslinkable gelatin methacrylate (GelMA).

Support-less ceramic 3D printing of bioceramic structures using a hydrogel bath.

Volumetric bone tissue defects are beyond the intrinsic regenerative capacity of bone tissue. With the recent development of ceramic 3D printing, various bioceramic scaffolds that can induce bone regeneration are being actively developed. However, hierarchical bone is complex, with overhanging structures that require additional sacrificial support during ceramic 3D printing.

Multifunctional bone substitute using carbon dot and 3D printed calcium-deficient hydroxyapatite scaffolds for osteoclast inhibition and fluorescence imaging.

Multifunctional bone substitute materials (BSM) have gained considerable attention with the exponential increase in aging populations. The development of hybrid materials for diagnosis and therapy of bone-related diseases and dysfunctions, especially, has been a significant challenge in the biological and the biomedical field, due to the shortage of agents with specificity and selectivity toward bone. In this study, a hybrid material, referred as Alen-CDs@CDHA, fabricated from alendronate-conjugated carbon dots (Alen-CDs) and calcium-deficient hydroxyapatite (CDHA, the mineral component of bones) scaffolds is offered as a novel multifunctional BSM for in vivo osteoclasts deactivation and fluorescence imaging.

Selective Detection of an Infection Biomarker by an Osteo-Friend Scaffold: Development of a Multifunctional Artificial Bone Substitute.

Developments in three-dimensional (3D) printing technologies have led to many potential applications in various biomedical fields, especially artificial bone substitutes (ABSs). However, due to the characteristics of artificial materials, biocompatibility and infection remain issues. Here, multifunctional ABSs have been designed to overcome these issues by the inclusion of a biochemical modality that allows simultaneous detection of an infection biomarker by osteo-friend 3D scaffolds.

Multifunctional Calcium-Deficient Hydroxyl Apatite-Alginate Core-Shell-Structured Bone Substitutes as Cell and Drug Delivery Vehicles for Bone Tissue Regeneration.

In this work, we fabricated unique coiled-structured bioceramics contained in hydrogel beads for simultaneous drug and cell delivery using a combination of bone cement chemistry and bioprinting and characterized them. The core of the calcium-deficient hydroxyl apatite (CDHA) contains quercetin, which is a representative phytoestrogen isolated from onions and apples, to control the metabolism of bone tissue regeneration through sustained release over a long period of time. The shell consists of an alginate hydrogel that includes preosteoblast MC3T3-E1 cells.

Bone-targeting carbon dots: effect of nitrogen-doping on binding affinity.

Novel fluorescent carbon dots (CDs) for bone imaging were fabricated a facile hydrothermal method using alendronate in the absence of a nitrogen-doping precursor to enhance bone affinity. One-step synthesized alendronate-based CDs (Alen-CDs) had strong binding activity for calcium-deficient hydroxyapatite (CDHA, the mineral component of bones) scaffold, rat femur, and bone structures of live zebrafish. This was attributed to the bisphosphonate group present on the CD surface, even after carbonization.

Fast and sensitive near-infrared fluorescent probes for ALP detection and 3d printed calcium phosphate scaffold imaging in vivo.

Alkaline phosphatase (ALP) is a critical biological marker for osteoblast activity during early osteoblast differentiation, but few biologically compatible methods are available for its detection. Here, we describe the discovery of highly sensitive and rapidly responsive novel near-infrared (NIR) fluorescent probes (NIR-Phos-1, NIR-Phos-2) for the fluorescent detection of ALP. ALP cleaves the phosphate group from the NIR skeleton and substantially alters its photophysical properties, therefore generating a large "turn-on" fluorescent signal resulted from the catalytic hydrolysis on fluorogenic moiety.

Effect of the biodegradation rate controlled by pore structures in magnesium phosphate ceramic scaffolds on bone tissue regeneration in vivo.

Unlabelled: Similar to calcium phosphates, magnesium phosphate (MgP) ceramics have been shown to be biocompatible and support favorable conditions for bone cells. Micropores below 25μm (MgP25), between 25 and 53μm (MgP53), or no micropores (MgP0) were introduced into MgP scaffolds using different sizes of an NaCl template. The porosities of MgP25 and MgP53 were found to be higher than that of MgP0 because of their micro-sized pores.

A simultaneous 3D printing process for the fabrication of bioceramic and cell-laden hydrogel core/shell scaffolds with potential application in bone tissue regeneration.

A novel process was developed to fabricate core/shell-structured 3D scaffolds, made of calcium-deficient hydroxyapatite (CDHA) and alginate laden with pre-osteoblast MC3T3-E1 cells, through a combination of cement chemistry, dual paste-extruding deposition (PED), and cell printing. The cement reaction of calcium phosphates replaced the typical sintering process of the ceramic scaffold fabrication after the simultaneous printing of the ceramics and cell-laden hydrogel. The alginate crosslinking process was divided into two steps using different concentrations of CaCl, during and after 3D printing, in order to obtain a stable 3D core/shell structure and high cell viability.