Osteoinductive Scaffolds Research Articles

Improving Phase Compatibility of PLA-PCL Matrix-Droplet Blend Using CNC/PCL-PEG-PCL Triblock Copolymer to Prepare Porous 3D Osteoinductive Scaffolds

Improving Phase Compatibility of PLA-PCL Matrix-Droplet Blend Using CNC/PCL-PEG-PCL Triblock Copolymer to Prepare Porous 3D Osteoinductive Scaffolds

Osteoinductive potential of graphene and graphene oxide for bone tissue engineering: a comparative study

BackgroundBone defects, especially critical-size bone defects, and their repair pose a treatment challenge. Osteoinductive scaffolds have gained importance given their potential in bone tissue engineering applications.MethodsPolycaprolactone (PCL) scaffolds are used for their morphological, physical, cell-compatible and osteoinductive properties. The PCL scaffolds were prepared by electrospinning, and the surface was modified by layer-by-layer deposition using either graphene or graphene oxide.ResultsGraphene oxide-coated PCL (PCL-GO) scaffolds showed a trend for enhanced physical properties such as fibre diameter, wettability and mechanical properties, yield strength, and tensile strength, compared to graphene-modified PCL scaffolds (PCL-GP). However, the surface roughness of PCL-GP scaffolds showed a higher trend than PCL-GO scaffolds. In vitro studies showed that both scaffolds were cell-compatible. Graphene oxide on PCL scaffold showed a trend for enhanced osteogenic differentiation of human umbilical cord Wharton’s jelly-derived Mesenchymal Stem Cells without any differentiation media than graphene on PCL scaffolds after 21 days.ConclusionGraphene oxide showed a trend for higher mineralisation, but this trend is not statistically significant. Therefore, graphene and graphene oxide have the potential for bone regeneration and tissue engineering applications. Future in vivo studies and clinical trials are warranted to justify their ultimate clinical use.Graphical abstract

Prioritizing Biomaterial Driven Clinical Bioactivity Over Designing Intricacy during Bioprinting of Trabecular Microarchitecture: A Clinician's Perspective.

Bone tissue engineering has witnessed a historical shift from three perspectives. From a biomaterial perspective, materials have now become smarter and dynamic; from a bioengineering perspective the bioprinting techniques have now advanced to 4D bioprinting; and from a clinical perspective scaffold bioactivity has progressed toward enhanced osteoinductive scaffolds driven by intricate biomechanical, biophysical, biochemical, and biological cues. Though all of these advancements are indicative of improvised scaffold engineering, a pivotal question regarding the critical role and need of designing and replicating the intricacies of trabecular microarchitecture for enhanced, clinically appreciable osteoangiogenicity needs to be answered. This review hence critically evaluates the rationale and the need of investing substantial effort into designing complex microarchitectures amidst the era of "smart biomaterials" and dynamic 4D bioprinting aimed toward enhancing clinically appreciable bioactivity. The article explores the concept of integrating intricate designs into a scaffold microarchitecture to bolster bioactivity and the practical challenges encountered in 3D bioprinting of complex designs and meticulously examines the pivotal role of biomaterials in scaffold bioactivity, proposing a comprehensive approach to bioprinting geared toward achieving clinical bioactivity and striking a judicious balance between design intricacy and functional outcomes in bone bioprinting.

Extrusion-based 3D printing of osteoinductive scaffolds with a spongiosa-inspired structure.

Critical-sized bone defects resulting from trauma, inflammation, and tumor resections are individual in their size and shape. Implants for the treatment of such defects have to consider biomechanical and biomedical factors, as well as the individual conditions within the implantation site. In this context, 3D printing technologies offer new possibilities to design and produce patient-specific implants reflecting the outer shape and internal structure of the replaced bone tissue. The selection or modification of materials used in 3D printing enables the adaption of the implant, by enhancing the osteoinductive or biomechanical properties. In this study, scaffolds with bone spongiosa-inspired structure for extrusion-based 3D printing were generated. The computer aided design process resulted in an up scaled and simplified version of the bone spongiosa. To enhance the osteoinductive properties of the 3D printed construct, polycaprolactone (PCL) was combined with 20% (wt) calcium phosphate nano powder (CaP). The implants were designed in form of a ring structure and revealed an irregular and interconnected porous structure with a calculated porosity of 35.2% and a compression strength within the range of the natural cancellous bone. The implants were assessed in terms of biocompatibility and osteoinductivity using the osteosarcoma cell line MG63 and patient-derived mesenchymal stem cells in selected experiments. Cell growth and differentiation over 14days were monitored using confocal laser scanning microscopy, scanning electron microscopy, deoxyribonucleic acid (DNA) quantification, gene expression analysis, and quantitative assessment of calcification. MG63 cells and human mesenchymal stem cells (hMSC) adhered to the printed implants and revealed a typical elongated morphology as indicated by microscopy. Using DNA quantification, no differences for PCL or PCL-CaP in the initial adhesion of MG63 cells were observed, while the PCL-based scaffolds favored cell proliferation in the early phases of culture up to 7days. In contrast, on PCL-CaP, cell proliferation for MG63 cells was not evident, while data from PCR and the levels of calcification, or alkaline phosphatase activity, indicated osteogenic differentiation within the PCL-CaP constructs over time. For hMSC, the highest levels in the total calcium content were observed for the PCL-CaP constructs, thus underlining the osteoinductive properties.

Bone regeneration in implant dentistry: Which are the factors affecting the clinical outcome?

The key factors that are needed for bone regeneration to take place include cells (osteoprogenitor and immune-inflammatory cells), a scaffold (blood clot) that facilitates the deposition of the bone matrix, signaling molecules, blood supply, and mechanical stability. However, even when these principles are met, the overall amount of regenerated bone, its stability over time and the incidence of complications may significantly vary. This manuscript provides a critical review on the main local and systemic factors that may have an impact on bone regeneration, trying to focus, whenever possible, on bone regeneration simultaneous to implant placement to treat bone dehiscence/fenestration defects or for bone contouring. In the future, it is likely that bone tissue engineering will change our approach to bone regeneration in implant dentistry by replacing the current biomaterials with osteoinductive scaffolds combined with cells and mechanical/soluble factors and by employing immunomodulatory materials that can both modulate the immune response and control other bone regeneration processes such as osteogenesis, osteoclastogenesis, or inflammation. However, there are currently important knowledge gaps on the biology of osseous formation and on the factors that can influence it that require further investigation. It is recommended that future studies should combine traditional clinical and radiographic assessments with non-invasive imaging and with patient-reported outcome measures. We also envisage that the integration of multi-omics approaches will help uncover the mechanisms responsible for the variability in regenerative outcomes observed in clinical practice.

EXTRUSION-BASED PRINTING OF OSTEOINDUCTIVE SCAFFOLDS USING CALCIUM PHOSPHATE

Critical-sized bone defects can result from trauma, inflammation, and tumor resection. Such bone defects, often have irregular shapes, resulting in the need for new technologies to produce suitable implants. Bioprinting is an additive manufacturing method to create complex and individualised bone constructs, which can already include vital cells.In this study, we established an extrusion-based printing technology to produce osteoinductive scaffolds based on polycaprolactone (PCL) combined with calcium phosphate, which is known to induce osteogenic differentiation of stem cells.The model was created in python based on the signed distance functions. The shape of the 3D model is a ring with a diameter of 20 mm and a height of 10 mm with a spongiosa-like structure. The interconnected irregular pores have a diameter of 2 mm +/− 0.2 mm standard deviation.Extrusion-based printing was performed using the BIO X6. To produce the bioink, PCL (80 kDa) was combined with calcium phosphate nanopowder (> 150 nm particle size) under heating. After printing, 5 × 106 hMSC were seeded on the construct using a rotating incubator.We were able to print a highly accurate ring construct with an interconnected pore structure. The PCL combined with calcium phosphate particles resulted in a precise printed construct, which corresponded to the 3D model. The bioink containing calcium phosphate nanoparticles had a higher printing accuracy compared to PCL alone. We found that hMSC cultured on the construct settled in close proximity to the calcium phosphate particles. The hMSC were vital for 22 days on the construct as demonstrated by life/dead staining.The extrusion printing technology enables to print a mechanically stable construct with a spongiosa-like structure. The porous PCL ring could serve as an outer matrix for implants, providing the construct the stability of natural bone. To extend this technology and to improve the implant properties, a biologised inner structure will be integrated into the scaffold in the future.

Engineering of an Osteoinductive and Growth Factor-Free Injectable Bone-Like Microgel for Bone Regeneration.

Bone autografts remain the gold standard for bone grafting surgeries despite having increased donor site morbidity and limited availability. Bone morphogenetic protein-loaded grafts represent another successful commercial alternative. However, the therapeutic use of recombinant growth factors has been associated with significant adverse clinical outcomes. This highlights the need to develop biomaterials that closely approximate the structure and composition of bone autografts, which are inherently osteoinductive and biologically active with embedded living cells, without the need for added supplements. Here, injectable growth factor-free bone-like tissue constructs are developed, that closely approximate the cellular, structural, and chemical composition of bone autografts. It is demonstrated that these micro-constructs are inherently osteogenic, and demonstrate the ability to stimulate mineralized tissue formation and regenerate bone in critical-sized defects in-vivo. Furthermore, the mechanisms that allow human mesenchymal stem cells (hMSCs) to be highly osteogenic in these constructs, despite the lack of osteoinductive supplements, are assessed, whereby Yes activated protein (YAP) nuclear localization and adenosine signaling appear to regulate osteogenic cell differentiation. The findings represent a step toward a new class of minimally invasive, injectable, and inherently osteoinductive scaffolds, which are regenerative by virtue of their ability to mimic the tissue cellular and extracellular microenvironment, thus showing promise for clinical applications in regenerative engineering.

Chitosan/Hydroxyapatite Scaffolds with P28 as a Promising Osteoinductive Scaffold for Bone Healing Applications

Despite bone’s inherent ability to heal, large bone defects remain a major clinical concern. This study proposes an off-the-shelf treatment combining chitosan/hydroxyapatite (CS/HAp) scaffolds, covalently linked with either bone morphogenetic protein-2 (BMP-2) or its related peptide P28 via a UV crosslinking process. Although covalently binding the growth factors was reported as a great alternative to the conventionally physical adsorption and encapsulation methods, this method presents the risk of altering the molecular activity and interaction of the growth factors. Therefore, alkaline phosphatase (ALP) activity and alizarin red staining (ARS) with a quantitative cetylpyridinium chloride (CPC) assay were conducted to validate that our photo-crosslinking fabrication method did not interfere with the functionality of the growth factors. The ALP activity of C2C12 with 100 µg/mL P28 was found to be comparable to 0.5 µg/mL BMP-2 after two weeks, where 0.001 U/mL was recorded for both treatments. The C2C12 cultured with CS/HAp/BMP-2 and CS/HAp/P28 scaffolds also showed an increased ALP activity compared to the negative control. ARS-CPC assay presented the highest optical density in 0.3 µg/mL BMP-2 and 50 µg/mL P28, while the highest intensity of ARS was observed in C2C12 cultured with CS/HAp/BMP-2 and CS/HAp/P28 scaffolds compared to the negative controls. The osteoconductive capability of this delivery system was then investigated through a rat femoral condyle defect model, where the new bone mineral density and the bone volume increased for all CS/HAp scaffolds compared to the collagen sponge control treatment. The histological assessment showed a favourable bone regeneration efficacy of the CS/HAp/P28 compared to the CS/HAp/BMP-2 treatment, thus showing the use of CS/HAp scaffolds with P28 as a promising osteoinductive scaffold for bone healing applications.

A Doubly Fmoc-Protected Aspartic Acid Self-Assembles into Hydrogels Suitable for Bone Tissue Engineering.

Hydrogels have been used as scaffolds for biomineralization in tissue engineering and regenerative medicine for the repair and treatment of many tissue types. In the present work, we studied an amino acid-based material that is attached to protecting groups and self-assembles into biocompatible and stable nanostructures that are suitable for tissue engineering applications. Specifically, the doubly protected aspartic residue (Asp) with fluorenyl methoxycarbonyl (Fmoc) protecting groups have been shown to lead to the formation of well-ordered fibrous structures. Many amino acids and small peptides which are modified with protecting groups display relatively fast self-assembly and exhibit remarkable physicochemical properties leading to three-dimensional (3D) networks, the trapping of solvent molecules, and forming hydrogels. In this study, the self-assembling fibrous structures are targeted toward calcium binding and act as nucleation points for the binding of the available phosphate groups. The cell viability, proliferation, and osteogenic differentiation of pre-osteoblastic cells cultured on the formed hydrogel under various conditions demonstrate that hydrogel formation in CaCl2 and CaCl2-Na2HPO4 solutions lead to calcium ion binding onto the hydrogels and enrichment with phosphate groups, respectively, rendering these mechanically stable hydrogels osteoinductive scaffolds for bone tissue engineering.

Fucoidan-Incorporated Composite Scaffold Stimulates Osteogenic Differentiation of Mesenchymal Stem Cells for Bone Tissue Engineering.

Globally, millions of bone graft procedures are being performed by clinicians annually to treat the rising prevalence of bone defects. Here, the study designed a fucoidan from Sargassum ilicifolium incorporated in an osteo-inductive scaffold comprising calcium crosslinked sodium alginate-nano hydroxyapatite-nano graphene oxide (Alg-HA-GO-F), which tends to serve as a bone graft substitute. The physiochemical characterization that includes FT-IR, XRD, and TGA confirms the structural integration between the materials. The SEM and AFM reveal highly suitable surface properties, such as porosity and nanoscale roughness. The incorporation of GO enhanced the mechanical strength of the Alg-HA-GO-F. The findings demonstrate the slower degradation and improved protein adsorption in the fucoidan-loaded scaffolds. The slow and sustained release of fucoidan in PBS for 120 h provides the developed system with an added advantage. The apatite formation ability of Alg-HA-GO-F in the SBF solution predicts the scaffold’s osteointegration and bone-bonding capability. In vitro studies using C3H10T1/2 revealed a 1.5X times greater cell proliferation in the fucoidan-loaded scaffold than in the control. Further, the results determined the augmented alkaline phosphatase and mineralization activity. The physical, structural, and enriching osteogenic potential results of Alg-HA-GO-F indicate that it can be a potential bone graft substitute for orthopedic applications.

Liver tissue-derived ECM loaded nanocellulose-alginate-TCP composite beads for accelerated bone regeneration

Guided bone regeneration with osteoinductive scaffolds is a competitive edge of tissue engineering due to faster and more consistent healing. In the present study, we developed such composite beads with nanocellulose reinforced alginate hydrogel that carried β-tricalcium phosphate (β-TCP) nano-powder and liver-derived extracellular matrix (ECM) from porcine. Interestingly, it was observed that the beads’ group containing ECM-β-TCP-alginate-nanocellulose (ETAC) was more cytocompatible than the others comprised of β-TCP-alginate-nanocellulose (TAC) and alginate-nanocellulose (AC). Cell attachment on ETAC beads was dramatically increased with time. In parallel with in vitro results, ETAC beads produced uniform cortical and cancellous bone in the femur defect model of rabbits within 2 months. Although the group TAC also produced noticeable bone in the defect site, the healing quality was improved and regeneration was faster after adding ECM. This conclusion was not only confirmed by micro-anatomical analysis but also demonstrated with x-ray microtomography. In addition, the characteristic moldable and injectable properties made ETAC a promising scaffold for clinical applications.

HIF signaling: A new propellant in bone regeneration.

Bone tissue destruction leads to severe pain, physical flaws, and loss of motility. Bone repair using biocompatible and osteo-inductive scaffolds is regarded as a viable and potential therapeutic approach. However, for large-scale bone regeneration, oxygen and nutrient supply have become limiting factors. Further, a considerable need exists for recruited cell activities and blood vessel growth. Hypoxia-inducible factor (HIF) signaling pathways induced by hypoxia are involved in angiogenesis and osteogenesis. As an important transcription factor, HIF-1 functions by modulating vital genes, such as VEGF, PDK1, and EPO, and is a crucial regulator that influences the final fate of bone regeneration. Collectively, to achieve better osteogenesis results, the in-depth molecular mechanisms that underpin the links between materials, cells, and HIF signaling pathways must be determined. This review aimed to provide an in-depth insight into recent progress in HIF-regulated bone regeneration. Hypoxia and cellular oxygen-sensing mechanisms and their correlations with osteogenesis were determined, and recent studies on hypoxia-inducing and hypoxia-mimicking strategies were briefly described. Finally, the potential applications of HIF signaling in bone regeneration were highlighted. This review provides theoretical support for establishing a novel and viable bone repair strategy in the clinic by harnessing HIF signaling.

Laponite/amoxicillin-functionalized PLA nanofibrous as osteoinductive and antibacterial scaffolds

In this study, Amoxicillin (AMX) was loaded on laponite (LAP) nanoplates and then immobilized on the surface of electrospun polylactic acid (PLA) nanofibers to fabricate scaffolds with osteoinductive and antibacterial activities. The highest loading efficiency (49%) was obtained when the concentrations of AMX and LAP were 3 mg/mL and 1 mg/mL, respectively. FTIR and XRD spectroscopies and zeta potentiometry confirmed the successful encapsulating of AMX within LAP nanoplates. The immobilization of AMX-loaded LAPs on the surface of PLA nanofibers was verified by SEM and FTIR spectroscopy. In vitro release study showed a two-phase AMX release profile for the scaffolds; an initial burst release within the first 48 h and a later sustained release up to 21 days. In vitro antibacterial tests against Staphylococcus aureus and Escherichia coli presented the ability of scaffolds to inhibit the growth of both bacteria. The biocompatibility assays revealed the attachment and viability of human bone marrow mesenchymal stem cells (hBMSCs) cultured on the surface of scaffolds (p ≤ 0.05). The increased ALKALINE PHOSPHATASE (ALP) activity (p ≤ 0.001), calcium deposition, and expression of ALP and OSTEONECTIN genes indicated the osteoinductivity of functionalized scaffolds for hBMSCs. These LAP/AMX-functionalized scaffolds might be desirable candida for the treatment of bone defects.

Immediately Implantable Extracellular Matrix-Enriched Osteoinductive Hydrogel-Laden 3d-Printed Scaffold for Promoting Vascularized Bone Regeneration in Vivo

Immediately Implantable Extracellular Matrix-Enriched Osteoinductive Hydrogel-Laden 3d-Printed Scaffold for Promoting Vascularized Bone Regeneration in Vivo

Polydopamine treatment of chitosan nanofibers for the conception of osteoinductive scaffolds for bone reconstruction

We report the influence of treatment time of electrospun chitosan nanofibers (CHT NFs) in dopamine hydrochloride bath (2 mg.mL−1 in 10 mM Tris buffer, pH 8.5) on the extent of the polydopamine (pDA) coating on NFs surface. The reaction was characterized by FTIR and SEM analysis and the cytocompatibility of the scaffolds toward MT3C3-E1 cells was assessed. Biomimetic deposition of hydroxyapatite (HA) in 1.5xSBF batch was investigated by SEM-EDS and XRD. Samples treated in dopamine bath during 2 h promoted the structural stability of NFs in PBS, provided optimal cytocompatibility and induced the in vitro biomineralization from 6 days in 1.5xSBF. The XRD and SEM-EDS investigations confirmed formation of spherical-shaped particles composed of apatitic phase. Finally, this study shows that these NFs-pDA scaffolds prepared in the optimal experimental conditions defined here are promising candidates for application as osteoinductive scaffolds for bone regeneration applied to orthopedic and dental applications.

Retraction Note to: Mesenchymal stem cells seeded onto tissue-engineered osteoinductive scaffolds enhance the healing process of critical-sized radial bone defects in rat.

Long bone defects comprise one of the most prevalent clinical problems worldwide and the current bone grafting materials have major limitations to repair them. Although tremendous efforts have been made to repair critical-sized long bone defects in animal models, designing an optimal bone tissue-engineered substitute remains one of the main challenges. Hence, this study aims to closely mimic a natural bone healing process by a tissue-engineered construct including osteoinductive materials pre-seeded with bone marrow-derived mesenchymal stem cells (BMSCs). Bioactive glass (BG) was incorporated into the gelatin/nano-hydroxyapatite (G/nHAp) scaffold (conventional one) to improve the bone regeneration process via its osteoinductivity and angiogenic activity. The fabricated G/nHAp and gelatin/nano-hydroxyapatite/bioactive glass (G/nHAp/BG) scaffolds were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) and analyzed for porosity and degradation rate. The osteogenic capability of fabricated scaffolds with or without BMSCs was then evaluated in vitro and in vivo. Critical-sized radial bone defects in rats were randomly filled with cell-free and BMSC-seeded scaffolds, autograft and a group left empty without any treatment. In vitro analysis showed that the G/nHAp/BG scaffold significantly increased the expression level of osteogenic and angiogenic markers in comparison to the G/nHAp-treated and control groups (P < 0.05). Moreover, the defects treated with the BMSC-seeded scaffolds showed superior bone formation and structural properties compared to the cell-free scaffolds 4 and 12 weeks post surgery. The radiological and histomorphological properties of defects treated by BMSC-seeded scaffolds, especially the BMSC-seeded G/nHAp/BG scaffold, were comparable to those of the autograft group. It is concluded that the combination of osteoconductive materials (i.e., nHAp) with the bioactive ones such as bioactive glass can effectively accelerate the bone regeneration process. In addition, our results demonstrated that the BMSCs have the potential to drastically increase the bone regeneration ability of osteoinductive scaffolds.

Direct 3D Printing of Seashell Precursor toward Engineering a Multiphasic Calcium Phosphate Bone Graft

Multiphasic calcium phosphate (Ca-P) has widely been explored for bone graft replacement. This study represents a simple method of developing osteoinductive scaffolds by direct printing of seashell resources. The process demonstrates a coagulation-assisted extrusion-based three-dimensional (3D) printing process for rapid fabrication of multiphasic calcium phosphate-incorporated 3D scaffolds. These scaffolds demonstrated an interconnected open porous architecture with improved compressive strength and higher surface area. Multiphasic calcium phosphate (Ca-P) and hydroxyapatite present in the multi-scalar naturally resourced scaffold displayed differential protein adsorption, thus facilitating cell adhesion, migration, and differentiation, resulting in enhanced deposition of the extracellular matrix. The microstructural and physicochemical attributes of the scaffolds also lead to enhanced stem cell differentiation as witnessed from gene and protein expression analysis. Furthermore, the histological study of subcutaneous implantation evidently portrays promising biocompatibility without foreign body reaction. Neo-tissue in-growth was manifested with abundant blood vessels, thus indicative of excellent vascularization. Notably, cartilaginous and proteoglycan-rich tissue deposition indicated ectopic bone formation via an endochondral ossification pathway. The hierarchical interconnected porous architectural tribology accompanied with multiphasic calcium phosphate composition manifests its successful implication in enhancing stem cell differentiation and promoting excellent tissue in-growth, thus making it a plausible alternative in bone tissue engineering applications.

Bone Graft Biomineral Complex Coderived from Marine Biocalcification and Biosilicification.

Bone graft materials have been mainly developed based on inorganic materials, including calcium phosphate. However, these graft materials usually act as osteoconductive rather than osteoinductive scaffolds. To improve bone reconstruction, a combination of several materials has been proposed. However, there are still no alternatives that can completely replace the existing animal-derived bone graft materials. In this work, a marine-inspired biomineral complex was suggested as a potential bone graft material. The proposed biosilicified coccolithophore-derived coccoliths using bioengineered mussel adhesive proteins show osteopromotive ability through the synergistic effects of osteoconductivity from calcium carbonate and osteoinductivity from silica. Its possibility of use as a bone substitute was determined by evaluating the in vitro osteogenic behaviors of multipotent mesenchymal stem cells and in vivo bone regeneration in a rat calvarial defect model. Therefore, the marine-inspired biomineral complex developed in this study could be successfully used for bone tissue engineering.

Highly active biological dermal acellular tissue scaffold composite with human bone powder for bone regeneration

Regenerative medicine for bone tissue in the oral cavity aims to repair alveolar or jaw defects. An ideal, highly active, osteoinductive, three-dimensional scaffold that can effectively promote cell proliferation and differentiation has not been reported. This study evaluated the in vitro and in vivo efficacy of a biological macromolecule composite scaffold derived from porcine dermal matrix bone tissue decellularized using sodium deoxycholate technology. The composite scaffold was composed of a porcine dermal acellular tissue matrix and human bone powder. The bone powder/acellular tissue matrix (Bp/ATM) scaffold was porous with a porosity exceeding 70%. Bp/ATM provided an osteoinductive scaffold that recruited osteoblasts to the site of injury and promoted their differentiation to bone cells. The 50% (v/v) bone-scaffold mixture significantly accelerated mineralized matrix production and the expression of osteogenesis-related proteins during osteogenic differentiation in vitro. This mixture also enhanced bone regeneration at the defect site in vivo in a rat cranial defect model. These observations suggest that Bp/ATM forms a highly active osteoinductive and osteoconductive scaffold that is a promising biomaterial for bone regeneration.

Antibacterial, conductive, and osteocompatible polyorganophosphazene microscaffolds for the repair of infectious calvarial defect.

Many osteoconductive and osteoinductive scaffolds have been developed for promoting bone regeneration; however, failures would occur in osteogenesis when the defect area is significantly infected while the biomaterials have no antibacterial performances. Herein, a kind of multipurpose PATGP@PDA + Ag microspheres was prepared via emulsion method by using a conductive aniline tetramer (AT) substituted polyphosphazene (PATGP), followed by polydopamine (PDA) modification and silver nanoparticles (AgNPs) loading. The PATGP@PDA + Ag microspheres demonstrated a strong antibacterial activity against Staphylococcus aureus both in vitro and in vivo, while showing no cytotoxicity at an optimized AgNPs loading amount. Due to the electron-donor structure of the AT moieties, the PATGP@PDA + Ag microspheres displayed antioxidant capacities to scavenge reactive oxygen species (ROS). Due to their phosphorus-rich feature, the PATGP@PDA + Ag microspheres favored the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). As controls, nonconductive microspheres (PAGP@PDA, PAGP@PDA + Ag) were prepared similarly by using poly[(ethylalanine)(ethylglycyl)]phosphazene (PAGP). By co-implanting these microspheres with S. aureus into rat calvarial defects, among them, it was determined that the PATGP@PDA + Ag microspheres achieved the most abundant neo-bone formation, benefiting from their antibacterial, antioxidant and osteogenic activities. These results revealed that AgNPs loaded scaffolds made of conductive polyphosphazenes were promising for the regeneration of infected bone defects.