Ceramic Scaffolds Research Articles

Bone regeneration in ceramic scaffolds with variable concentrations of PDRN and rhBMP-2

This study evaluated the bone regeneration capacity and mechanical properties of block-type hydroxyapatite (HA)/tricalcium phosphate (TCP) scaffolds in response to different concentrations of polydeoxyribonucleotide (PDRN) and recombinant human bone morphogenic protein 2 (rhBMP-2). Thirty-two male white rabbits were used as a model of calvarial bone defect and classified into eight groups according to type and concentration of growth factor administered, viz., control group (only HA/TCP scaffold), scaffold + PDRN (0.1, 1, 5, and 10 mg/mL each) and scaffold + rhBMP-2 (0.01, 0.05, and 0.1 mg/mL each). The specimens were evaluated using histomorphometric and radiological analyses. Histomorphometric analyses indicated that the administration of PDRN did not increase bone formation. However, significant increases in bone formation were observed with the administration of rhBMP-2 at 0.05 and 0.10 mg/mL on week 8 compared to the control (p < 0.05). Radiological analyses revealed a significant increase in bone formation at week 8 with the administration of PDRN at 5 mg/mL and 10 mg/mL, and rhBMP-2 at 0.05 or 0.10 mg/mL compared to the control (p < 0.05). Our findings show that block-type HA/TCP scaffolds possess sufficient mechanical strength and bone regeneration capacity when used with optimal concentrations of growth factors.

3D printing of HAp/xSiO2 ceramic scaffolds for potential bone graft reconstruction

HAp has drawn great attention in recent years for its similarity to the inorganic component of bone and can be used as a biocompatible implant. However, the application is limited for its poor shape ability and low degradation ability. With the help of Digital Light Processing 3D printing technology, this study proposed a method for the fabrication of bone remodeling scaffolds with high complexity. In addition, this study found that the silica addition will help densify the HAp ceramic and make it transform to a more biodegradable TCP phase at low sintering temperature.

Controlled delivery of bone morphogenic protein-2-related peptide from mineralised extracellular matrix-based scaffold induces bone regeneration

Ideal bone tissue engineering scaffolds composed of extracellular matrix (ECM) require excellent osteoconductive ability to imitate the bone environment. We developed a mineralised tissue-derived ECM-modified true bone ceramic (TBC) scaffold for the delivery of aspartic acid-modified bone morphogenic protein-2 (BMP-2) peptide (P28) and assessed its osteogenic capacity. Decellularized ECM from porcine small intestinal submucosa (SIS) was coated onto the surface of TBC, followed by mineralisation modification (mSIS/TBC). P28 was subsequently immobilised onto the scaffolds in the absence of a crosslinker. The alkaline phosphatase activity and other osteogenic differentiation marker results showed that osteogenesis of the P28/mSIS/TBC scaffolds was significantly greater than that of the TBC and mSIS/TBC groups. In addition, to examine the osteoconductive capability of this system in vivo, we established a rat calvarial bone defect model and evaluated the new bone area and new blood vessel density. Histological observation showed that P28/mSIS/TBC exhibited favourable bone regeneration efficacy. This study proposes the use of mSIS/TBC loaded with P28 as a promising osteogenic scaffold for bone tissue engineering applications.

Digital light processing stereolithography of hydroxyapatite scaffolds with bone‐like architecture, permeability, and mechanical properties

AbstractThis work deals with the additive manufacturing and characterization of hydroxyapatite scaffolds mimicking the trabecular architecture of cancellous bone. A novel approach was proposed relying on stereolithographic technology, which builds foam‐like ceramic scaffolds by using three‐dimensional (3D) micro‐tomographic reconstructions of polymeric sponges as virtual templates for the manufacturing process. The layer‐by‐layer fabrication process involves the selective polymerization of a photocurable resin in which hydroxyapatite particles are homogeneously dispersed. Irradiation is performed by a dynamic mask that projects blue light onto the slurry. After sintering, highly‐porous hydroxyapatite scaffolds (total porosity ~0.80, pore size 100‐800 µm) replicating the 3D open‐cell architecture of the polymeric template as well as spongy bone were obtained. Intrinsic permeability of scaffolds was determined by measuring laminar airflow alternating pressure wave drops and was found to be within 0.75‐1.74 × 10−9 m2, which is comparable to the range of human cancellous bone. Compressive tests were also carried out in order to determine the strength (~1.60 MPa), elastic modulus (~513 MPa) and Weibull modulus (m = 2.2) of the scaffolds. Overall, the fabrication strategy used to print hydroxyapatite scaffolds (tomographic imaging combined with digital mirror device [DMD]‐based stereolithography) shows great promise for the development of porous bioceramics with bone‐like architecture and mass transport properties.

Highly porous Sr-doped TiO2 ceramics maintain compressive strength after grain boundary corrosion

Maintaining sufficient mechanical support during bone healing is an essential property for ceramic bone scaffolds. However, grain boundary (GB) dissolution may compromise the mechanical strength of polycrystalline ceramics in the physiological environment. Therefore, we investigated the GB formation and its impact on the compressive strength and corrosion behavior in TiO2 scaffolds doped with calcium and strontium. To alter the GB composition and densification process, sintering conditions were altered. Prolonged sintering times and increased sintering temperature led to improved densification and increased strength in Ca-doped scaffolds. However, dissolution of the resulting amorphous GBs caused a significant loss of compressive strength when exposed to an acidic environment. In contrast, a crystalline SrTiO3 GB phase present in Sr-doped scaffolds, for which increased sintering temperature combined with rapid cooling led to a significantly improved compressive strength. Formation of SrTiO3 crystals in the GBs maintained the strength for over 4 weeks in an acidic environment.

Fabrication and Characterization of Sr-doped Hydroxyapatite Porous Scaffold

Strontium (Sr) is a trace metal ion that exists in natural bones. It not only regulates metabolism but also promotes osteoblast differentiation and the formation of new bones. In this study, a new method was developed to prepare Sr-doped hydroxyapatite (HA) three-dimensional (3D) porous scaffolds. A preliminary scaffold was obtained by an extrusion 3D printing method using HA–sodium alginate composite slurry as printing ink. Then, the obtained scaffolds were immersed in a strontium chloride (SrCl2·6H2O) solution of different concentrations (1 wt.%, 5 wt.%, 10 wt.%, and 15 wt.%) for 24 h. Finally, the scaffolds were dried and then sintered at 1200°C to obtain the final scaffolds. The Sr-doped scaffolds were characterized by scanning electron microscopy, x-ray diffraction, Fourier-transform infrared spectroscopy, mechanical testing, and cell culture testing. The results show that the Sr-doped HA scaffold has better compactness and compressive strength than the HA-0Sr scaffold, and promotes cell proliferation and osteoblast differentiation. This indicates that the alternative method is suitable for preparing ion-doping ceramic scaffolds for bone tissue engineering.

Scaffold-Type Structure Dental Ceramics with Different Compositions Evaluated through Physicochemical Characteristics and Biosecurity Profiles.

The design and development of ceramic structures based on 3D scaffolding as dental bone substitutes has become a topic of great interest in the regenerative dentistry research area. In this regard, the present study focuses on the development of two scaffold-type structures obtained from different commercial dental ceramics by employing the foam replication method. At the same time, the study underlines the physicochemical features and the biological profiles of the newly developed scaffolds, compared to two traditional Cerabone® materials used for bone augmentation, by employing both the in vitro Alamar blue proliferation test at 24, 48 and 96 h poststimulation and the in ovo chick chorioallantoic membrane (CAM) assay. The data reveal that the newly developed scaffolds express comparable results with the traditional Cerabone® augmentation masses. In terms of network porosity, the scaffolds show higher pore interconnectivity compared to Cerabone® granules, whereas regarding the biosafety profile, all ceramic samples manifest good biocompatibility on primary human gingival fibroblasts (HGFs); however only the Cerabone® samples induced proliferation of HGF cells following exposure to concentrations of 5 and 10 µg/mL. Additionally, none of the test samples induce irritative activity on the vascular developing plexus. Thus, based on the current results, the preliminary biosecurity profile of ceramic scaffolds supports the usefulness for further testing of high relevance for their possible clinical dental applications.

3D CaP porous scaffolds with grooved surface topography obtained by the sol-gel method

The influence of surface topography on cellular behaviour and its importance for the development of three-dimensional scaffolds for bone tissue engineering are a topic of growing interest. To date, the introduction of topographical patterns into the surface of 3D porous ceramic scaffolds has proven difficult, due partly to the brittle nature of ceramic materials as well as the currently available fabrication technologies. In this study, a grooved pattern was introduced into the surface of 3D multilayer porous ceramic scaffolds by the chemical etching technique. The patterned scaffolds were characterised by X-Ray Diffraction (XRD), Scanning Electron Microscopy with Energy Dispersive X-Ray Spectroscopy (SEM-EDX) and Digital Holographic Microscopy (DHM). Their bioactivity was also evaluated in vitro by immersion in simulated body fluid (SBF) for 12 h, 1, 7, 14 and 21 days. Scaffolds were constituted mainly with a mixture of the calcium pyrophosphate (Ca2O7P2) and β-tricalcium phosphate (Ca₃(PO₄)₂) phases. The pyrophosphate on the external layer was dissolved as a result of the etching process, leaving grooves on the surface. Ridges and grooves were nano-/micrometric, with dimensions of around 900 nm–1.5 μm in width and 200 nm–300 nm in depth. Moreover, the mechanical properties and bioactive capacity of the patterned scaffolds were not affected by chemical etching, making them suitable to be used in bone tissue engineering.

Strong and tough bioinspired nacre-like B4C/Al functionally graded materials with eliminated abrupt interfaces

Due to multiple length-scale and gradient microstructures, numerous living organisms have optimized performance. Herein, inspired by the gradient structure of nacre, biomimetic materials with gradient microstructure were attempted to be created via overcoming the challenges of limited methods. The combination of layer-by-layer casting and gelation-freeze-drying were firstly used to produce ceramic scaffolds with continuously graded channels, followed by infiltrating molten alloy into the scaffolds, new B4C/2024Al bi-continuously functionally graded materials (FGMs) equipped with nacre-like and multicomponent gradient structures were developed. Since continuous ice crystals grew across the interface between layers and the around ceramic particles were rearranged during the solidification of the layered wet suspension, abrupt interfaces between layers were effectively eliminated in the scaffolds and final FGMs. Importantly, these unique structures not only provide an exceptional combination of strength and toughness but also allow for a smooth transition of properties. Our feasible approach paves a novel avenue to create FGMs in terms of biomimetic structures with high-performance.

The State of Starch/Hydroxyapatite Composite Scaffold in Bone Tissue Engineering with Consideration for Dielectric Measurement as an Alternative Characterization Technique.

Hydroxyapatite (HA) has been widely used as a scaffold in tissue engineering. HA possesses high mechanical stress and exhibits particularly excellent biocompatibility owing to its similarity to natural bone. Nonetheless, this ceramic scaffold has limited applications due to its apparent brittleness. Therefore, this had presented some difficulties when shaping implants out of HA and for sustaining a high mechanical load. Fortunately, these drawbacks can be improved by combining HA with other biomaterials. Starch was heavily considered for biomedical device applications in favor of its low cost, wide availability, and biocompatibility properties that complement HA. This review provides an insight into starch/HA composites used in the fabrication of bone tissue scaffolds and numerous factors that influence the scaffold properties. Moreover, an alternative characterization of scaffolds via dielectric and free space measurement as a potential contactless and nondestructive measurement method is also highlighted.

Fabrication of porous β-TCP/58S bioglass scaffolds via top-down DLP printing with high solid loading ceramic-resin slurry

High solid loading of ceramic slurry limits the wider use of digital light processing (DLP) in the production of porous ceramic scaffolds with advanced functions. The top-down digital light processing (DLP) system is a potential method to achieve ceramic-resin slurry with high solid loading. Porous β-tricalcium phosphate/58S bioglass (β-TCP/BG) scaffolds with high solid loading ceramic slurry were fabricated by the top-down DLP technique in this paper. Photosensitive β-TCP/BG-resin slurries with various solid loadings for DLP were developed and the effects of solid loading on viscosity and curing reactivity were evaluated. The microstructure, mechanical strength, porosity, and shrinkage of the composite scaffolds were then explored. The results show that the maximum viscosity of the β-TCP/BG-resin slurry for top-down DLP technique was 85.92 Pa s with a solid loading of 60 wt%. The cure depth and overgrowth tended to decrease with the solid loading. The curing depth exceeds 100 μm at each solid loading after 18000 ms irradiation time. The shaping error and sintering shrinkage of the porous structure were estimated, and it was found that the pore size and sintering shrinkage reaching a minimum value for the scaffolds fabricated by the slurry of 60 wt%. The compressive strength of the β-TCP/BG scaffolds increased with the solid loading increased, reaching a maximum value of 11.43 ± 0.4 MPa for the solid loading of 60 wt%. β-TCP/BG scaffolds exhibited an alkalescent pH environment and an improved ability of apatite-mineralization formation, meanwhile Ca, P and Si were gradually released from scaffolds. Furthermore, in vitro evaluation of β-TCP/BG scaffolds was carried out to assess the osteogenic capability. The composite scaffolds displayed intensifying biocompatibility and can facilitate osteoblast proliferation, adhesion, and differentiation. The β-TCP/BG composite scaffold fabricated by top-down DLP with high solid loading ceramic slurry could be considered as a promising alternative substitute even for load-bearing bone tissue engineering applications.

Silk fibroin and ceramic scaffolds: Comparative in vitro studies for bone regeneration.

Synthetic bone void fillers based on calcium ceramics are used to fill cavities in the bone and promote bone regeneration. More recently, silk fibroin (SF), a protein polymer obtained from Bombyx mori silkworm, has emerged as a promising material in bone void filling. In this work, we have compared the safety and efficacy of two types of silk fibroin‐based bone void fillers with currently used and commercially available ceramic bone void fillers (based on calcium sulphate, beta tricalcium phosphate, and beta tricalcium phosphate with hydroxyapatite). Further, we have also evaluated these two types of SF scaffolds, which have strikingly different structural attributes. The biocompatibility of these scaffolds was comparable as assessed by cytotoxicity assay, cellular adhesion assay, and immunogenic assay. Ability of the scaffolds to support differentiation of human mesenchymal stem cells (hMSCs) into an osteoblastic lineage was also evaluated in an in vitro differentiation experiment using reverse transcriptase polymerase chain reaction analysis. These results revealed that cells cultured on SF scaffolds exhibit higher expression of early to late markers such as Runx2, BMPs, collagen, osterix, osteopontin, and osteocalcin as compared with ceramic‐based scaffolds. This observation was further validated by studying the expression of alkaline phosphatase and calcium deposition. We also show that scaffolds made from same material of SF, but characterized by very different pore architectures, have diverse outcome in stem cell differentiation.

Ce/Sm/Sr-Incorporating Ceramic Scaffolds Obtained via Sol-Gel Route.

Three different inorganic scaffolds were obtained starting from the oxide system SiO2‒P2O5‒CaO‒MgO, to which Ce4+/Sm3+/Sr2+ cations were added in order to propose novel materials with potential application in the field of hard tissue engineering. Knowing the beneficial effects of each element, improved features in terms of mechanical properties, antibacterial activity and cellular response are expected. The compositions were processed in the form of scaffolds by a common sol-gel method, followed by a thermal treatment at 1000 and 1200 °C. The obtained samples were characterized from thermal, compositional, morphological and mechanical point of view. It was shown that each supplementary component triggers the modification of the crystalline phase composition, as well as microstructural details. Moreover, the shrinkage behavior is well correlated with the attained compression strength values. Sm was proven to be the best choice, since in addition to a superior mechanical resistance, a clear beneficial influence on the viability of 3T3 fibroblast cell line was observed.

Effect of hexagonal structure nanoparticles on the morphological performance of the ceramic scaffold using analytical oscillation response

Porous bony scaffolds are utilized to manage the growth and migration of cells from adjacent tissues to a defective position. In the current investigation, the effect of titanium oxide (TiO2) nanoparticles on mechanical and physical properties of porous bony implants made of polymeric polycaprolactone (PCL) is studied. The bio-nanocomposite scaffolds are prepared with composition of nanocrystalline hydroxyapatite (HA) and TiO2 powder using the freeze-drying technique for different weight fractions of TiO2 (0 wt%, 5 wt%, 10 wt%, and 15 wt%). In order to identify the microstructure and morphology of the fabricated porous bio-nanocomposites, the X-ray diffraction (XRD), atomic force microscope (AFM) and scanning electron microscopy (SEM) are employed. Also, the biocompatibility and biodegradability of the manufactured scaffolds are examined by placing them in a simulated body fluid (SBF) for 21 days, their weight and pH changes are measured. The rate of degradation of the PCL-HA scaffold can be controlled by varying the percentage of its constituent components. Due to an increasing growth and activity of bone cells and the apatite formation on the free surface of the fabricated bio-nanocomposite implants as well as their reasonable mechanical properties, they have the potential to be used as a bone substitute. Additionally, with the aid of the experimentally extracted mechanical properties of the scaffolds, the vibrational characteristics of a beam-type implant made of the proposed porous bio-nanocomposites are explored. The results obtained from SEM image indicate that the scaffolds produced by the employed method have high total porosity (70%–85%) and effective porosity. The pore size is obtained between 60 and 200 μm, which is desirable for the growth and propagation of bone cells. Also, it is revealed that the addition of TiO2 nanoparticles leads to reduce the rate of dissolution of the fabricated bio-nanocomposite scaffolds.

Micro-/Nano-Structured Ceramic Scaffolds That Mimic Natural Cancellous Bone.

Micro-/nano-structured scaffolds with a weight composition of 46.6% α-tricalcium phosphate (α-TCP)—53.4% silicocarnotite (SC) were synthesized by the polymer replica method. The scanning electron microscopy (SEM) analysis of the scaffolds and natural cancellous bone was performed for comparison purposes. Scaffolds were obtained at three cooling rates via the eutectoid temperature (50 °C/h, 16.5 °C/h, 5.5 °C/h), which allowed the surface nanostructure and mechanical strength to be controlled. Surface nanostructures were characterized by transmission electron microscopy (TEM) and Raman analysis. Both phases α-TCP and SC present in the scaffolds were well-identified, looked compact and dense, and had neither porosities nor cracks. The non-cytotoxic effect was evaluated in vitro by the proliferation ability of adult human mesenchymal stem cells (ah-MSCs) seeded on scaffold surfaces. There was no evidence for cytotoxicity and the number of cells increased with culture time. A dense cell-hydroxyapatite layer formed until 28 days. The SEM analysis suggested cell-mediated extracellular matrix formation. Finally, scaffolds were functionalized with the alkaline phosphatase enzyme (ALP) to achieve biological functionalization. The ALP was successfully grafted onto scaffolds, whose enzymatic activity was maintained. Scaffolds mimicked the micro-/nano-structure and chemical composition of natural cancellous bone by considering cell biology and biomolecule functionalization.

Tuning filament composition and microstructure of 3D-printed bioceramic scaffolds facilitate bone defect regeneration and repair.

It is still a challenge to optimize the component distribution and microporous structures in scaffolds for tailoring biodegradation (ion releasing) and enhancing bone defect repair within an expected time stage. Herein, the core–shell-typed nonstoichiometric wollastonite (4% and 10% Mg-doping calcium silicate; CSiMg4, CSiMg10) macroporous scaffolds with microporous shells (adding ∼10 μm PS microspheres into shell-layer slurry) were fabricated via 3D printing. The initial mechanical properties and bio-dissolution (ion releasing) in vitro, and osteogenic capacity in vivo of the bioceramic scaffolds were evaluated systematically. It was shown that endowing high-density micropores in the sparingly dissolvable CSiMg10 or dissolvable CSiMg4 shell layer inevitably led to nearly 30% reduction of compressive strength, but such micropores could readily tune the ion release behaviour of the scaffolds (CSiMg4@CSiMg10 vs. CSiMg4@CSiMg10-p; CSiMg10@CSiMg4 vs. CSiMg10@CSiMg4-p). Based on the in rabbit femoral bone defect repair model, the 3D μCT reconstruction and histological observation demonstrated that the CSiMg4@CSiMg10-p scaffolds displayed markedly higher osteogenic capability than the other scaffolds after 12 weeks of implantation. It demonstrated that core–shell bioceramic 3D printing technique can be developed to fabricate single-phase or biphasic bioactive ceramic scaffolds with accurately tailored filament biodegradation for promoting bone defect regeneration and repair in some specific pathological conditions.

Materials and Manufacturing Techniques for Polymeric and Ceramic Scaffolds Used in Implant Dentistry

Preventive and regenerative techniques have been suggested to minimize the aesthetic and functional effects caused by intraoral bone defects, enabling the installation of dental implants. Among them, porous three-dimensional structures (scaffolds) composed mainly of bioabsorbable ceramics, such as hydroxyapatite (HAp) and β-tricalcium phosphate (β-TCP) stand out for reducing the use of autogenous, homogeneous, and xenogenous bone grafts and their unwanted effects. In order to stimulate bone formation, biodegradable polymers such as cellulose, collagen, glycosaminoglycans, polylactic acid (PLA), polyvinyl alcohol (PVA), poly-ε-caprolactone (PCL), polyglycolic acid (PGA), polyhydroxylbutyrate (PHB), polypropylenofumarate (PPF), polylactic-co-glycolic acid (PLGA), and poly L-co-D, L lactic acid (PLDLA) have also been studied. More recently, hybrid scaffolds can combine the tunable macro/microporosity and osteoinductive properties of ceramic materials with the chemical/physical properties of biodegradable polymers. Various methods are suggested for the manufacture of scaffolds with adequate porosity, such as conventional and additive manufacturing techniques and, more recently, 3D and 4D printing. The purpose of this manuscript is to review features concerning biomaterials, scaffolds macro and microstructure, fabrication techniques, as well as the potential interaction of the scaffolds with the human body.

Personalized Baghdadite scaffolds: stereolithography, mechanics and in vivo testing

An ongoing challenge in the field of orthopedics is to produce a clinically relevant synthetic ceramic scaffold for the treatment of ‘critical-sized’ bone defects, which cannot heal without intervention. We had developed a bioactive ceramic (baghdadite, Ca₃ZrSi₂O₉) and demonstrated its outstanding bioactivity using traditional manufacturing techniques. Here, we report on the development of a versatile stereolithography printing technology that enabled fabrication of anatomically-shaped and -sized Baghdadite scaffolds. We assessed the in vivo bioactivity of these scaffolds in co-delivering of bone morphogenetic protein-2 (BMP2) and zoledronic acid (ZA) through bioresorbable coatings to induce bone formation and increase retention in a rat model of heterotopic ossification. Micro-computed tomography, histology, mechanical tests pre- and post-implantation, and mechanical modelling were used to assess bone ingrowth and its effects on the mechanics of the scaffolds. Bone ingrowth and the consequent mechanical properties of the scaffolds improved with increasing BMP2 dose. Co-delivery of ZA with BMP2 further improved this outcome. The significant bone formation within the scaffolds functionalized with 10 µg BMP2 and 2 µg ZA made them 2.3 × stiffer and 2.7 × stronger post-implantation and turned these inherently brittle scaffolds into a tough and deformable material. The effects of bone ingrowth on the mechanical properties of scaffolds were captured in a mechanical model that can be used in future clinical studies for non-destructive evaluation of scaffold's stiffness and strength as new bone forms. These results support the practical utilization of our versatile stereolithographic printing methods and BMP2/ZA functionalization to create fit-for-purpose personalized implants for clinical trials. Statement of significanceIn this study, we addressed a long-standing challenge of developing a ceramic printing technology that enables fabrication of customizable anatomically-shaped and -sized bioceramic scaffolds with precise internal architectures using an inexpensive desktop printer. We also addressed another challenge related to delivery of pharmaceuticals. BMP2, currently available as a bone-inducing bioactive protein, is clinically administered in a collagen scaffold that has limited moldability and poor mechanical properties. The comparably stiffer and stronger 3D printed personalized Baghdadite scaffolds developed here can be readily functionalized with bioresorbable coatings containing BMP2 ± ZA. These innovations considerably improve on the prior art and are scalable for use in human surgery.

3D-printed, bioactive ceramic scaffold with rhBMP-2 in treating critical femoral bone defects in rabbits using the induced membrane technique.

Although autogenous bone grafts are an optimal filling material for the induced membrane technique, limited availability and complications at the harvest site have created a need for alternative graft materials. We aimed to investigate the effect of an rhBMP-2-coated, 3D-printed, macro/microporous CaO-SiO2 -P2 O5 -B2 O3 bioactive ceramic scaffold in the treatment of critical femoral bone defects in rabbits using the induced membrane technique. A 15-mm segmental bone defect was made in the metadiaphyseal area of the distal femur of 14 rabbits. The defect was filled with polymethylmethacrylatecement and stabilized with a 2.0 mm locking plate. After the membrane matured for 4 weeks, the scaffold was implanted in two randomized groups: Group A (3D-printed bioceramic scaffold) and Group B (3D-printed, bioceramic scaffold with rhBMP-2). Eight weeks after implantation, the radiographic assessment showed that the healing rate of the defect was significantly higher in Group B (7/7, 100%) than in Group A (2/7, 29%). The mean volume of new bone formation around and inside the scaffold doubled in Group B compared to that in Group A. The mean static and dynamic stiffness were significantly higher in Group B. Histological examination revealed newly formed bone in both groups. Extensive cortical bone formation along the scaffold was found in Group B. Successful bone reconstruction in critical-sized bone defects could be obtained using rhBMP-2-coated, 3D-printed, macro/microporous bioactive ceramic scaffolds. This grafting material demonstrated potential as an alternative graft material in the induced membrane technique for reconstructing critical-sized bone defects.

Influence of Mesenchymal Stem Cell Sources on Their Regenerative Capacities on Different Surfaces.

Current gold-standard strategies for bone regeneration do not achieve the optimal recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells—such as mesenchymal stem cells (MSCs)—and bioactive ceramic scaffolds—such as calcium phosphate-based (CaPs) bioceramics—seem promising. The biological properties of MSCs are influenced by the tissue source. This study aims to define the optimal MSC source and construct (i.e., the MSC–CaP combination) for clinical application in bone regeneration. A previous iTRAQ analysis generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow, and dental pulp, then cultured both on a plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate), to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) presented the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs demonstrated the greatest capacity to colonise the bioceramics. Furthermore, the results demonstrated a trend that DPSCs had the most robust increase in ALP activity. Regarding CaPs, β-tricalcium phosphate obtained the best viability results, while hydroxyapatite had the highest ALP activity values. Therefore, we propose DPSCs as suitable MSCs for cell-based bone regeneration strategies.