Tricalcium Phosphate Scaffolds Research Articles

Silver and silicon doped βTCP scaffolds with gentamicin or ceftazidime loaded P(3HB) coatings as multifunctional biomaterials for bone regeneration

The risk of bacterial infections is a significant challenge faced frequently in the use of implants or scaffolds for bone regeneration. Therefore, this study focusses on the development and characterisation of novel β tricalcium phosphate (βTCP) scaffolds co-doped with silver and silicon, along with composites coated with antibiotic-loaded poly(3-hydroxybutyrate) (P(3HB)) layers. The successful incorporation of silver and silicon dopants while maintaining the formation of βTCP phase was confirmed using X-ray fluorescence (XRF), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS) analysis. The developed materials demonstrated comparable total and open porosity (∼64–70 vol%), suggesting high interconnectivity between pores conducive to nutrient transport and tissue repair. The increase in compressive strength was achieved for both doped (4.73 ± 0.79 MPa) and P(3HB) coated (5.79 ± 0.92 MPa) scaffolds due to the fine bioceramic microstructure and polymeric coating. Silver and silicon-modified βTCP demonstrated enhanced growth inhibition of Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and Gram-positive (Staphylococcus aureus) bacterial strains in vitro compared to the pure βTCP. P(3HB) coatings, enriched with gentamicin or ceftazidime, exhibited burst and sustained release of the antibiotics from the scaffolds up to 120 h further intensifying the bacteria-killing capability, with evident inhibition zones observed in vitro. Moreover, the composites exhibited apatite-forming ability, suggesting their bioactive potential. In vivo evaluation using Caenorhabditis elegans demonstrated the lack of toxicity of the tested materials. The simultaneous incorporation of the dopants and antibiotic-loaded P(3HB) coatings not only offer a dual antibacterial approach but may also facilitate bone regeneration. However, further in vitro and in vivo investigations are needed to assess their potential in clinical application.

Mesenchymal Stem Cell Exosomes Enhance Posterolateral Spinal Fusion in a Rat Model.

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.

Osteogenically committed hUCMSCs-derived exosomes promote the recovery of critical-sized bone defects with enhanced osteogenic properties.

Low viability of seed cells and the concern about biosafety restrict the application of cell-based tissue-engineered bone (TEB). Exosomes that bear similar bioactivities to donor cells display strong stability and low immunogenicity. Human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-Exos) show therapeutic efficacy in various diseases. However, little is known whether hUCMSCs-Exos can be used to construct TEB to repair bone defects. Herein, PM-Exos and OM-Exos were separately harvested from hUCMSCs which were cultured in proliferation medium (PM) or osteogenic induction medium (OM). A series of in-vitro studies were performed to evaluate the bioactivities of human bone marrow mesenchymal stem cells (hBMSCs) when co-cultured with PM-Exos or OM-Exos. Differential microRNAs (miRNAs) between PM-Exos and OM-Exos were sequenced and analyzed. Furthermore, PM-Exos and OM-Exos were incorporated in 3D printed tricalcium phosphate scaffolds to build TEBs for the repair of critical-sized calvarial bone defects in rats. Results showed that PM-Exos and OM-Exos bore similar morphology and size. They expressed representative surface markers of exosomes and could be internalized by hBMSCs to promote cellular migration and proliferation. OM-Exos outweighed PM-Exos in accelerating the osteogenic differentiation of hBMSCs, which might be attributed to the differentially expressed miRNAs. Furthermore, OM-Exos sustainably released from the scaffolds, and the resultant TEB showed a better reparative outcome than that of the PM-Exos group. Our study found that exosomes isolated from osteogenically committed hUCMSCs prominently facilitated the osteogenic differentiation of hBMSCs. TEB grafts functionalized by OM-Exos bear a promising application potential for the repair of large bone defects.

3D Printed SiO2-Tricalcium Phosphate Scaffolds Loaded with Carvacrol Nanoparticles for Bone Tissue Engineering Application.

Bone damage resulting from trauma or aging poses challenges in clinical settings that need to be addressed using bone tissue engineering (BTE). Carvacrol (CA) possesses anti-inflammatory, anticancer, and antibacterial properties. Limited solubility and physicochemical stability restrict its biological activity, requiring a stable carrier system for delivery. Here, we investigate the utilization of a three-dimensional printed (3DP) SiO2-doped tricalcium phosphate (TCP) scaffold functionalized with carvacrol-loaded lipid nanoparticles (CA-LNPs) to improve bone health. It exhibits a negative surface charge with an entrapment efficiency of ∼97% and size ∼129 nm with polydispersity index (PDI) and zeta potential values of 0.18 and -16 mV, respectively. CA-LNPs exhibit higher and long-term release over 35 days. The CA-LNP loaded SiO2-doped TCP scaffold demonstrates improved antibacterial properties against Staphylococcus aureus and Pseudomonas aeruginosa by >90% reduction in bacterial growth. Functionalized scaffolds result in 3-fold decrease and 2-fold increase in osteosarcoma and osteoblast cell viability, respectively. These findings highlight the therapeutic potential of the CA-LNP loaded SiO2-doped TCP scaffold for bone defect treatment.

Effects of light exposure intensity and time on printing quality and compressive strength of β-TCP scaffolds fabricated with digital light processing

Digital light processing (DLP), derived from stereolithography (SL), is a lithography-based additive manufacturing (AM) process that offers the ability to tailor scaffold shape, size, material, and biometrics of fabricated scaffolds to patient requirements. The additive manufacturing of tricalcium phosphate (TCP) bioceramic scaffolds via DLP is explored in the proceeding research paper. Particularly, the role of exposure intensity and exposure time on resultant scaffold quality and mechanical properties is studied. Increased exposure intensity results in an increased deviation from the designed lattice structure and thus an increase in compressive strength. Scaffolds produced with the highest exposure intensity, resulted in a 27.6 % error increase in mean beam diameter, resulting from an increased scattering effect, penetration depth, and over-curing of peripheral slurry. TCP scaffolds with an exposure time of 3.5 s and exposure intensity of 40 mW/cm2 possessed the highest print accuracy, resulting in the lowest average compressive strength – 82 MPa for the scaffolds of cube structure and 48 MPa for the ones of I-WP structure. Statement of significanceDigital light processing (DLP) is an effective additive manufacturing (AM) method applicable for bioceramics. This study focuses on the influence of light exposure intensity on scaffold quality and compressive strength. The increase of exposure intensity can improve the compressive strength with the sacrifice of structure accuracy. The conclusions of this study can provide insights into the relationship of DLP printing parameters and scaffolds quality.

Scaffolds based on β tricalcium phosphate and polyhydroxyalkanoates as biodegradable and bioactive bone substitutes with enhanced physicochemical properties

Polyhydroxyalkanoates (PHAs) are biocompatible and biodegradable bacterial-origin polyesters, which have recently emerged as a potential prosperous coating for bioceramic scaffolds. However, biopolymers often have properties inferior to commercially available polymers, and thus blending seems to be an efficient method to tailor their characteristics. In our study poly(3-hydroxybutyrate) (P(3HB)) and medium chain length PHA (mcl-PHA) blends were used as coatings on β tricalcium phosphate (βTCP) scaffolds. The influence of the coating type on the physicochemical properties of composites was investigated using various techniques such as X-ray diffraction (XRD), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis with differential scanning calorimetry (TG/DSC), scanning electron microscopy (SEM), atomic force microscopy (AFM), wettability measurements, ultra high-performance liquid chromatography with and mass spectrometry (UHPLC-MS) and in vitro studies. It has been demonstrated that blends with various amounts of brittle P(3HB) and viscous mcl-PHA can serve as coatings on βTCP scaffolds, modulating their physicochemical properties. Macroporous scaffolds covered with blends possessed high open porosity (~ 65 vol%) and improved compressive strength (up to 4.9 ± 0.9 MPa). It has been shown that their wettability can be tailored by modifying composition of blends, making the surface more hydrophobic with increasing amount of mcl-PHA. The highest amount of mcl-PHA was shown to significantly influence the degradation of the composites which may be a valuable feature in the case of customized scaffolds for the controlled release of bioactive substances. Moreover, UHPLC-MS analysis revealed that PHAs degrade to hydroxy acids and their oligomers, which may serve as potentially nourishing compounds for surrounding tissues. According to in vitro biocompatibility tests on mouse preosteoblasts, all evaluated scaffolds were nontoxic. The greater the surface hydrophilicity, the better cell adhesion and proliferation were observed.

Sinus augmentation with poly(ε)caprolactone-β tricalcium phosphate scaffolds, mesenchymal stem cells and platelet rich plasma for one-stage dental implantation in minipigs.

This study evaluated the efficacy of a tube-shaped poly(ε) caprolactone - β tricalcium phosphate (PCL-TCP) scaffold with the incorporation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) and platelet-rich plasma (PRP) for bone regeneration in the procedure of single-stage sinus augmentation and dental implantation in minipigs. Implants were placed in the bilateral sides of the maxillary sinuses of 5 minipigs and allocated to a PCL-TCP+hUCMSCs+PRP group (n=5), a PCL-TCP+PRP group (n=5), and a PCL-TCP-only group (n=6). After 12 weeks, bone regeneration was evaluated with soft X-rays, micro-computed tomography, fluorescence microscopy, and histomorphometric analysis. Four implants failed (2 each in the PCL-TCP+hUCMSCs+PRP and PCL-TCP+hUCMSC groups). An analysis of the grayscale levels and bone-implant contact ratio showed significantly higher mean values in the PCL-TCP+hUCMSCs+PRP than in the PCL-TCP group (P=0.045 and P=0.016, respectively). In fluoromicroscopic images, new bone formation around the outer surfaces of the scaffolds was observed in the PCL-TCP+hUCMSCs+PRP group, suggesting a tenting effect of the specially designed scaffolds. Bone regeneration at the scaffold-implant interfaces was observed in all 3 groups. Using a tube-shaped, honeycombed PCL-TCP scaffold with hUCMSCs and PRP may serve to enhance bone formation and dental implants' osseointegration in the procedure of simultaneous sinus lifting and dental implantation.

In vitro biological evaluation of epigallocatechin gallate (EGCG) release from three-dimensional printed (3DP) calcium phosphate bone scaffolds.

Three-dimensional printed (3DP) tricalcium phosphate (TCP) scaffolds can guide bone regeneration, especially for patient-specific defect repair applications in low-load bearing sites. Epigallocatechin gallate (EGCG), a green tea compound, has gained attention as a safer alternative treatment for bone disorders. The 3DP TCP scaffold is designed for localized EGCG delivery, which can enhance in vitro osteogenic ability, anti-osteoclastogenic activity, vascularization formation, and chemoprevention. In the cocultures of human bone marrow-derived mesenchymal stem cells (hMSCs) and monocytes (THP-1), EGCG release enhances osteogenic differentiation of hMSCs at day 16 compared to the control; this is indicated by a 2.8- and 4.0-fold upregulation of Runt-related transcription factor 2 (Runx2) and bone gamma-carboxyglutamic acid-containing protein (BGLAP), the early and late osteoblast differentiation marker expressions. However, EGCG significantly downregulates the receptor activator of nuclear factor-κB ligand (RANKL) expression by 7.0-fold, indicating that EGCG suppresses RANKL-induced osteoclast maturation. EGCG also stimulates endothelial tube formation at as early as 3 hours when human umbilical vein endothelial cells (HUVECs) grow on Matrigel. It reduces human osteosarcoma MG-63 cell viability by 66% compared to the control at day 11. An in vitro release kinetics study demonstrates that EGCG shows a ∼64% release within a day followed by a sustained release in the physiological environment (pH 7.4) because its phenolic hydroxyl groups are easily deprotonated at physiological pH. These findings contribute to developing a multifunctional scaffold for the treatment of low load-bearing patient-specific bone defects after trauma and tumor excision.

In vivo and In vitro properties evaluation of curcumin loaded MgO doped 3D printed TCP scaffolds.

The lack of site-specific chemotherapeutic agents to treat bone malignancy throws a significant challenge in the design of a delivery vehicle. The major scientific question posed in this study is, can we utilize curcumin-loaded magnesium oxide (MgO) doped 3D printed tricalcium phosphate (TCP) bone grafts as a localized delivery system that improves early stage in vivo osseointegration and in vitro chemoprevention, antibacterial properties? We have utilized curcumin as an alternative natural chemopreventive agent for bone cancer-specific delivery after direct incorporation on the 3D printed tricalcium phosphate (TCP) bone grafts. The addition of MgO as a dopant to TCP leads to ∼1.3 times enhancement in compressive strength. The designed drug delivery system shows up to ∼22% curcumin release in a physiological pH of 7.4 after 30 days. The presence of curcumin leads to up to ∼8.5 times reduction in osteosarcoma viability. In vitro results indicate that these scaffolds significantly enhance bone-forming osteoblast cells while reducing the bone-resorbing osteoclast cells. The in vivo rat distal femur model surgery followed by histological assessment with H&E, vWF, and Movat pentachrome staining results show that the designed scaffolds lead to new bone formation (up to ∼2.5 times higher than the control) after successful implantation. The presence of MgO and curcumin results in up to ∼71% antibacterial efficacy against osteomyelitis causing S. aureus. These 3D printed osteogenic and chemopreventive scaffolds can be utilized in patient-specific low load-bearing defect sites.

Assessment of tricalcium phosphate/titanium dioxide (TCP/TiO2) nanocomposite scaffold compared with bone autograft and hydroxyapatite (HA) on the healing of segmental femur bone defect in rabbits

Bone healing is a tissue process after a surgical operation. Many formulated materials have been designed for improving these procedures. The purpose of this study was to evaluate the effectiveness of nanocomposite tricalcium phosphate scaffolds combined with Titanium dioxide scaffold (TCP/TiO2) for femoral defects regeneration in rabbits. We studied 80 mature male New Zealand white rabbits weighing between 3 and 3.5 kg. Rabbits were subdivided into four groups. Anesthesia was performed before surgical operation by 50 mg/kg Ketamine 10% and 5 mg/kg xylazine 5% intramuscularly. We inducted a 6 × 5 mm diameter cylinder defect on the femur. Animals were separated into four trial groups of 20 animals each. After defecting, the experimental groups include control, autograft, hydroxyapatite, and TCP/TiO2 (received pure nanocomposite TCP/TiO2 material). A pathologist evaluated the sections on days 15, 30, 45, and 60 after surgery. The improvement of new and lamellar bone formation was the best in the nanocomposite TCP/TiO2 group at various point times, especially 60 days after surgery. We found that TCP/TiO2 nanocomposite has a significant improving function in the remodeling of bone in the defect areas.Graphical abstract

A Medical-Grade Polycaprolactone and Tricalcium Phosphate Scaffold System With Corticoperiosteal Tissue Transfer for the Reconstruction of Acquired Calvarial Defects in Adults: Protocol for a Single-Arm Feasibility Trial.

BackgroundLarge skull defects present a reconstructive challenge. Conventional cranioplasty options include autologous bone grafts, vascularized bone, metals, synthetic ceramics, and polymers. Autologous options are affected by resorption and residual contour deformities. Synthetic materials may be customized via digital planning and 3D printing, but they all carry a risk of implant exposure, failure, and infection, which increases when the defect is large. These complications can be a threat to life. Without reconstruction, patients with cranial defects may experience headaches and stigmatization. The protection of the brain necessitates lifelong helmet use, which is also stigmatizing.ObjectiveOur clinical trial will formally study a hybridized technique's capacity to reconstruct large calvarial defects.MethodsA hybridized technique that draws on the benefits of autologous and synthetic materials has been developed by the research team. This involves wrapping a biodegradable, ultrastructured, 3D-printed scaffold made of medical-grade polycaprolactone and tricalcium phosphate in a vascularized, autotransplanted periosteum to exploit the capacity of vascularized periostea to regenerate bone. In vitro, the scaffold system supports cell attachment, migration, and proliferation with slow but sustained degradation to permit host tissue regeneration and the replacement of the scaffold. The in vivo compatibility of this scaffold system is robust—the base material has been used clinically as a resorbable suture material for decades. The importance of scaffold vascularization, which is inextricably linked to bone regeneration, is underappreciated. A variety of methods have been described to address this, including scaffold prelamination and axial vascularization via arteriovenous loops and autotransplanted flaps. However, none of these directly promote bone regeneration.ResultsWe expect to have results before the end of 2023. As of December 2020, we have enrolled 3 participants for the study.ConclusionsThe regenerative matching axial vascularization technique may be an alternative method of reconstruction for large calvarial defects. It involves performing a vascularized free tissue transfer and using a bioresorbable, 3D-printed scaffold to promote and support bone regeneration (termed the regenerative matching axial vascularization technique). This technique may be used to reconstruct skull bone defects that were previously thought to be unreconstructable, reduce the risk of implant-related complications, and achieve consistent outcomes in cranioplasty. This must now be tested in prospective clinical trials.Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12620001171909; https://tinyurl.com/4rakccb3International Registered Report Identifier (IRRID)DERR1-10.2196/36111

A low-cost approach to develop silica doped Tricalcium Phosphate (TCP) scaffold by valorizing animal bone waste and rice husk for tissue engineering applications

In the present study Hydroxyapatite (HAp) derived Tricalcium Phosphate (TCP) and Silica (SiO2) based scaffold was successfully fabricated for the first time by effective utilizing various waste such as animal waste bone (AWB) and rice husk (RH) as a source of HAp and SiO2 respectively. Scaffold development involved simple steps comprising of segregation of waste materials followed by sample preparation through die compaction and sintering (1000 °C and 1300 °C). Advanced characterization techniques like XRD, SEM, TEM, and FTIR were employed to study the properties of the waste materials as well as the developed composite scaffold. The presence of silica from RH combines with the HAp during high temperature sintering and initiates the phenomenon of phase transformation of HAp to TCP along with the formation of a glassy phase. The extent of phase transformation increases as the wt% of RH increases. XRD analysis revealed the development of different phases. SEM microstructure shows that the addition of silica restricts the grain growth and supports the formation of crystalline glassy phase termed as Si-TCP. FTIR results confirmed the presence of phosphate, carbonate, and hydroxyl groups in the sintered samples. The porosity of the scaffold was in the range of 34–61% and the compressive strength was up to 4.1 MPa. The SEM images of scaffold dipped in simulated body fluid (SBF) shows formation of apatite layer throughout the surface. The bioactivity of the scaffold was highly influenced by the addition of silica in the HAp matrix. The apatite forming ability of the developed porous was much greater than that of pure HAp for the same incubation period. The obtained properties of the developed scaffold are comparable to that of natural bone. Thus the present work creates an opportunity to use AWB for the development of composite for tissue engineering applications.

Effect of different MgFe2O4 contents on 3D gel‐printed porous TCP–MgFe2O4 composite scaffolds

AbstractMagnetic materials have shown significant influence in the process of bone regeneration. In order to combine the bone repairing capability of tricalcium phosphate (TCP) ceramic with magnetic material, porous TCP–MgFe2O4 composite scaffolds were successfully prepared by three‐dimensional (3D) gel‐printing technology, and the effect of different MgFe2O4 contents on TCP–MgFe2O4 composite scaffolds was studied. The viscosity of printing slurry prepared with polyvinyl alcohol as binder decreased with the increase of shear rate, showing shear thinning. Results show that following with MgFe2O4 content increasing from 30 to 70 wt%, the compressive strength of the composite scaffolds increased from 8.45 to 10.58 MPa, the saturation magnetization increased from 3.07 to 7.20 emu/g, and the weight loss rate of degradation in vitro increased from 1.83% to 2.1% after 4 weeks, respectively. Live and dead staining shows that MC3T3‐E1 cells had better proliferation on TCP–MgFe2O4 composite scaffolds than TCP scaffolds. Compared with pure TCP scaffolds, the addition of MgFe2O4 improves the comprehensive performance of scaffolds and meets the application requirements of bone repairing.

The effect of pore morphology and agarose coating on mechanical properties of tricalcium phosphate scaffolds

Three-dimensional biocompatible porous structures can be fabricated using different methods. However, the biological and mechanical behaviors of scaffolds are the center of focus in bone tissue engineering. In this study, tricalcium phosphate scaffolds with similar porosity contents but different pore morphologies were fabricated using two different techniques, namely, the replica method and the pore-forming agent method. The samples fabricated using the pore-forming agent showed more than two times higher compressive and bending strengths and more than three times higher compressive moduli. Furthermore, a thin layer of agarose coating improved the compressive and bending strength of both types of ceramic scaffolds. Subsequently, the samples’ capability to guide biomineralization was evaluated by immersion into a simulated body fluid that developed Ca-P nano-platelets formation and enhanced the compressive strength. Finally, the tetrazolium-based colorimetric (MTT) assay was used to evaluate L929 cell viability and proliferation on all the samples and confirmed that cell behavior was not affected by pore morphology or agarose coating. In summary, samples produced by the use of the pore-forming agent showed higher potential to be applied as bone scaffolds in tissue engineering applications.

Evaluation of imaging setups for quantitative phase contrast nanoCT of mineralized biomaterials.

X-ray nano-tomography with phase contrast (nanoCT) using synchrotron radiation is a powerful tool to non-destructively investigate 3D material properties at the nanoscale. In large bone lesions, such as severe bone fractures, bone cancer or other diseases, bone grafts substituting the lost bone might be necessary. Such grafts can be of biological origin or be composed of a synthetic bone substitute. The long-term functioning of artificial bone substitutes depends on many factors. Synchrotron nanoCT imaging has great potential to contribute to further the understanding of integration of implants into bone tissue by imaging the spatial interaction between bone tissue and implant, and by accessing the interface between implant material and bone tissue. With this aim, a methodology for evaluating the image quality is presented for in-line phase contrast nanoCT images of bone scaffold samples. A PMMA-embedded tricalcium phosphate scaffold was used with both a closed and an open porosity structure and bone ingrowths as a representative system of three known materials. Parameters such as spatial resolution and signal-to-noise ratio were extracted and used to explore and quantitatively compare the effects of implementation choices in the imaging setup, such as camera technology and imaging energy, on the resulting image quality. Increasing the X-ray energy from 17.5 keV to 29.6 keV leads to a notable improvement in image quality regardless of the camera technology used, with the two tested camera setups performing at a comparable level when the recorded intensity was kept constant.

Preparation of photothermal-sensitive PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds for bone defect repair

The repair of bone defects has long been a challenging and significant health question. Here, collagen hydrogel incorporating platelet-derived growth factor (PDGF)-loaded photopolymerizable ZIF-8-PDA nanoparticles (PDGF@ZIF-8-PDA@COL hydrogel) was prepared and perfused into 3D printed poly (lactide-co-glycolide)-tricalcium phosphate (PLGA-TCP) scaffolds. The resulting PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds were applied as a bone substitute for cranial bone defect repair. The photopolymerizable ZIF-8-PDA nanoparticles had a mean size of 226.2 ± 5.3 nm with photothermal conversion capacity. PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds showed a slower release of PDGF compared to PDGF release from collagen hydrogels. The composite scaffolds exhibited excellent antibacterial properties and good in vitro osteoconductive capacity. The osteoconductive activities of PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds were also investigated in a rat cranial bone defect model in vivo by micro-CT imaging, hematoxylin and eosin staining, Masson’s trichrome staining, and immunohistochemical staining of osteogenesis-related markers. The PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds accelerated cranial bone formation and gradually degraded over time. All these results provided strong evidence that PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds might be a promising system for bone defect repair.

In vivo evaluation of tricalcium phosphate scaffold for cranial prosthesis application

Tricalcium phosphate beta phase (β-TCP) is a promising bioceramic that stimulates the formation of bone tissue due to its chemical composition, which is similar to those of bones and teeth, showing promising osseointegration and osteoinduction results. Its main applications are in the regeneration and stimulation of cortical and trabecular bone tissue. β-TCP can be used in the human body in different ways: scaffolds, coatings, or granules. In the present investigation, we analyzed the implant bioactivity effects of a β-TCP scaffold in the skull at different timeslots. The scaffolds were characterized physically and chemically before being implanted in vivo. The authors evaluated possible behavioral consequences in cognitive and motor tests on Wistar rats during the time when the tricalcium phosphate scaffolds were reabsorbed, which stimulated the bone regeneration on the cranial defect. The results of the β-TCP scaffolds as skull implant in rats showed an excellent hydroxyapatite (HA) precipitation on the implant's surface, stimulating new bone formation in the defect zone without affecting the motor and cognitive abilities of the animals' during the six weeks after implantation.

Regenerative matching axial vascularisation of absorbable 3D-printed scaffold for large bone defects: A first in human series

BackgroundWe describe the first clinical series of a novel bone replacement technique based on regenerative matching axial vascularisation (RMAV). This was used in four cases: a tibial defect after treatment of osteomyelitis; a calvarial defect after trauma and failed titanium cranioplasty; a paediatric tibial defect after neoadjuvant chemotherapy and resection of Ewing sarcoma; and a paediatric mandibular deficiency resulting from congenital hemifacial microsomia. MethodAll patients underwent reconstruction with three-dimensional (3D)-printed medical-grade polycaprolactone and tricalcium phosphate (mPCL-TCP) scaffolds wrapped in vascularised free corticoperiosteal flaps. OutcomeFunctional volumes of load-sharing regenerate bone have formed in all cases after a moderate duration of follow-up. At 36 cm, case 1 remains the longest segment of load bearing bone ever successfully reconstructed. This technique offers an alternative to existing methods of large volume bone defect reconstruction that may be safe, reliable, and give predictable outcomes in challenging situations. It achieves this by using a bioresorbable scaffold to support and direct the growth of regenerate bone, driven by RMAV. ConclusionThis technique may facilitate the reconstruction of bone defects previously thought unreconstructable, reduce the risk of long-term implant-related complications and achieve these outcomes in a hostile environment. These potential benefits must now be formally tested in prospective clinical trials.

Ginger and Garlic Extracts Enhance Osteogenesis in 3D Printed Calcium Phosphate Bone Scaffolds with Bimodal Pore Distribution.

Natural medicines have long been used to treat physiological ailments where both ginger (gingerol) and garlic (allicin) are key players in immune system promotion, reduction in blood pressure, and lowering inflammation response. With their efficacy in bone healing, these compounds have great value as medicinal additives in bone scaffolds for localized treatment to support tissue formation, along with providing their natural therapeutic benefits. Utilization of 3D-printed (3DP) bone tissue engineering scaffolds as drug delivery vehicles for ginger and garlic extracts enables patient specificity in bone defect applications with enhanced osseointegration. Our objective is to understand their combined efficacy on osteogenesis when released from 3DP calcium phosphate bone scaffolds designed with a bimodal pore distribution. With a porous core and dense exterior, the resulting scaffolds have good mechanical integrity with 10 ± 1 MPa compressive strengths. Results show that ginger + garlic extracts released from bone scaffolds enhance their osteogenic potential through on site drug delivery. Both compounds exhibit exponential drug release profiles which fit Weibull distribution equations. The release of ginger extract also increases osteoblast proliferation by 59%. Both compounds show decreased osteoclast resorption activity, with a greater than 20% reduction in pit area on sample surfaces. Ginger + garlic extract induces a twofold increase in early osteoid tissue formation in vivo at week 4, in addition to a 30% increase in total bone area and a 90% increase in osteocytes with respect to control 3DP tricalcium phosphate scaffolds. Late-stage bone healing at week 10 reveals healthy angiogenic tissue, a twofold higher bone mineralization, and significant enhancement of type I collagen formation in the presence of ginger and garlic extracts. Naturally sourced ginger and garlic extracts provide osteogenic promotion and improved bone tissue in-growth in a patient-specific 3DP scaffold biomedical device for low load-bearing bone tissue engineering and dental applications.

Effects of Vitamin A (Retinol) Release from Calcium Phosphate Matrices and Porous 3D Printed Scaffolds on Bone Cell Proliferation and Maturation

Vitamin A is a fat-soluble compound widely known for vision health. Highly variable reports on its effects on bone health have necessitated further research to truly understand its role on bone cell proliferation. Retinol, one bioactive form of vitamin A, is incorporated into synthetic bone graft scaffolds for low load-bearing clinical bone treatment. The objective of this work is to understand the effects of retinol on osteoblast and osteoclast cells when embedded within calcium phosphate matrices, including interconnected porous 3D printed tricalcium phosphate scaffolds. Results show that hydrophobic retinol can be released from bone scaffolds when a combination of biodegradable polymers, polycaprolactone and polyethylene glycol, are employed as drug carriers. The release of retinol in vitro can support a 20 ± 1% increase in osteoblast (bone-forming) cell proliferation with proper cell adhesion and filopodial extensions. Osteoclast cell morphology is necrosed and torn with a reduction in proliferation at approximately 6 ± 1% when retinol is present. In addition, inhibition of osteoclastic resorption pit bays is noted using scanning electron microscopy. With the scaffolds' round pore interconnectivity facilitating retinol release, this system can provide an alternative to traditional bone grafts while additionally supporting bone healing through enhanced osteoblast cell proliferation and inhibition of osteoclast resorption activity.