Enhanced Bone Tissue Regeneration Research Articles

THE ROLE OF PERICYTES IN BONE TISSUE REGENERATION AND THERAPEUTIC APPLICATIONS

The regeneration of massive bone defects poses a significant challenge in traumatology and orthopedics, often requiring bone grafting procedures following tumor resection, surgery, or severe injury. Current treatment methods include autologous and allogeneic bone grafts, as well as bone substitutes. While autologous transplantation is considered the standard, it is limited by donor site morbidity and availability. Allogeneic transplantation presents risks such as graft rejection and disease transmission. Bone substitutes may not fully restore bone defects. Tissue-engineered biomaterials offer promise for effective regeneration, utilizing stem cells, growth factors, and scaffolds. Adipose tissue, rich in mesenchymal stem cells and perivascular stem cells (pericytes), is a promising cell source for tissue engineering. This thesis explores the therapeutic potential of pericytes combined with various biological carriers and stimulating factors to enhance bone tissue regeneration. Pericytes, contractile cells surrounding small blood vessels, are crucial for vessel integrity and blood flow regulation. They express markers like α-SMA and PDGFR-β and participate in angiogenesis, immune function, and tissue repair. Interactions with endothelial cells via signaling pathways involving molecules like VEGF and TGF-β are vital for vessel formation and stability. With their multipotent nature, pericytes show promise for regenerative medicine. Ongoing research is essential to address challenges in pericyte biology, including identification and understanding their roles in tissue regeneration. Studies highlight the potential of adipose tissue-derived pericytes in bone regeneration, particularly CD146+ pericytes, showing efficacy in spinal fusion and nonunion fracture treatment when combined with DBM. Preclinical studies confirm their effectiveness, especially when incorporated into various scaffold materials. Clinical studies using adipose-derived stem cells and autologous microfragmented adipose tissue have shown promise, with pericyte-enriched fractions holding potential for improved outcomes. Future research into pericyte application, combined with growth factors and scaffolds, could significantly advance bone tissue regeneration and regenerative medicine. Human pericytes show promise for bone tissue regeneration due to their mesenchymal stem cell properties and role in vascular stabilization. Injectable hydrogels are crucial for bone tissue engineering, with various biomaterials developed for this purpose. Studies using injectable hydrogels with pericytes have demonstrated their efficacy in accelerating bone regeneration in different models. Further advancements in injectable hydrogel technology incorporating stem cells and osteoinductive factors are needed for more efficient bone tissue restoration.

Enhancement of Bone Repair in Diabetic Rats with Metformin-Modified Silicified Collagen Scaffolds.

Regenerating bone defects in diabetic rats presents a significant challenge due to the detrimental effects of reactive oxygen species and impaired autophagy on bone healing. To address these issues, a metformin-modified biomimetic silicified collagen scaffold is developed utilizing the principles of biomimetic silicification. In vitro and in vivo experiments demonstrated that the scaffold enhanced bone tissue regeneration within the diabetic microenvironment through the release of dual bio-factors. Further analysis reveals a potential therapeutic mechanism whereby these dual bio-factors synergistically promoted osteogenesis in areas of diabetic bone defects by improving mitochondrial autophagy and maintaining redox balance. The present study provides critical insights into the advancement of tissue engineering strategies aimed at bone regeneration in diabetic patients. The study also sheds light on the underlying biological mechanisms.

Additive manufacturing of bioactive and biodegradable poly (lactic acid)-tricalcium phosphate scaffolds modified with zinc oxide for guided bone tissue repair

Bioactive and biodegradable scaffolds that mimic the natural extracellular matrix of bone serve as temporary structures to guide new bone tissue growth. In this study, 3D-printed scaffolds composed of poly (lactic acid) (PLA)-tricalcium phosphate (TCP) (90-10 wt.%) were modified with 1%, 5%, and 10 wt.% of ZnO to enhance bone tissue regeneration. A commercial chain extender named Joncryl was incorporated alongside ZnO to ensure the printability of the composites. Filaments were manufactured using a twin-screw extruder and subsequently used to print 3D scaffolds via fused filament fabrication (FFF). The scaffolds exhibited a homogeneous distribution of ZnO and TCP particles, a reproducible structure with 300 μm pores, and mechanical properties suitable for bone tissue engineering, with an elastic modulus around 100 MPa. The addition of ZnO resulted in enhanced surface roughness on the scaffolds, particularly for ZnO microparticles, achieving values up to 241 nm. This rougher topography was responsible for enhancing protein adsorption on the scaffolds, with an increase of up to 85% compared to the PLA-TCP matrix. Biological analyses demonstrated that the presence of ZnO promotes mesenchymal stem cell (MSC) proliferation and differentiation into osteoblasts. Alkaline phosphatase (ALP) activity, an important indicator of early osteogenic differentiation, increased up to 29%. The PLA-TCP composite containing 5% ZnO microparticles exhibited an optimized degradation rate and enhanced bioactivity, indicating its promising potential for bone repair applications.

3D Printed Calcium Phosphate Physiochemically Dual-Regulating Pro-Osteogenesis and Antiosteolysis for Enhancing Bone Tissue Regeneration.

Osteoblasts and osteoclasts are two of the most important types of cells in bone repair, and their bone-forming and bone-resorbing activities influence the process of bone repair. In this study, we proposed a physicochemical bidirectional regulation strategy via ration by physically utilizing hydroxyapatite nanopatterning to recruit and induce MSCs osteogenic differentiation and by chemically inhibiting osteolysis activity through the loaded zoledronate. The nanorod-like hydroxyapatite coating was fabricated via a modified hydrothermal process while the zoledronic acid was loaded through the chelation within the calcium ions. The fabrication of a hydroxyapatite/zoledronic acid composite biomaterial. This biomaterial promotes bone tissue regeneration by physically utilizing hydroxyapatite nanopatterning to recruit and induce MSCs osteogenic differentiation and by chemically inhibiting osteolysis activity through the loaded zoledronate. The nanorod-like hydroxyapatite coating was fabricated via a modified hydrothermal process while the zoledronic acid was loaded through the chelation within the calcium ions. The in vitro results tested on MSCs and RAW 246.7 indicated that the hydroxyapatite enhanced cells' physical sensing system, therefore enhancing the osteogenesis. At the same time the zoledronic acid inhibited osteolysis by downregulating the RANK-related genes. This research provides a promising strategy for enhancing bone regeneration and contributes to the field of orthopedic implants.

Additively Manufactured Porous Metallic Implants and Their Surface Modification for Biomedical Applications: A Review

The evolution of three dimensional (3D) printed porous metallic biomaterials and their clinical applications are currently receiving much consideration. Many research works have been focused on the shaping by 3D printing of lightweight metal implants with improved mechanical properties. In the same way, the effect of surface finishes on roughness and porosity distribution on biological properties is still debated. Therefore, several factors need to be addressed and revisited in this context. This review focuses on the importance of porous metallic implant design and its relationship with biological and mechanical properties. First, the additive manufacturing (AM) techniques for bio-inert metals and alloys will be discussed. The review will then introduce the most efficient surface treatments and coating approaches for biomedical porous metals to enhance bone tissue regeneration, prevent corrosion, reduce revision surgery and improve implant lifetime. A critical study of the various parameters impacting the biological properties will also be carried out in this review.

Biphasic bone substitutes coated with PLGA incorporating therapeutic ions Sr2+ and Mg2+: cytotoxicity cascade and in vivo response of immune and bone regeneration.

The incorporation of bioactive ions into biomaterials has gained significant attention as a strategy to enhance bone tissue regeneration on the molecular level. However, little knowledge exists about the effects of the addition of these ions on the immune response and especially on the most important cellular regulators, the macrophages. Thus, this study aimed to investigate the in vitro cytocompatibility and in vivo regulation of bone remodeling and material-related immune responses of a biphasic bone substitute (BBS) coated with metal ions (Sr2+/Mg2+) and PLGA, using the pure BBS as control group. Initially, two cytocompatible modified material variants were identified according to the in vitro results obtained following the DIN EN ISO 10993-5 protocol. The surface structure and ion release of both materials were characterized using SEM-EDX and ICP-OES. The materials were then implanted into Wistar rats for 10, 30, and 90days using a cranial defect model. Histopathological and histomorphometrical analyses were applied to evaluate material degradation, bone regeneration, osteoconductivity, and immune response. The findings revealed that in all study groups comparable new bone formation were found. However, during the early implantation period, the BBS_Sr2+ group exhibited significantly faster regeneration compared to the other two groups. Additionally, all materials induced comparable tissue and immune responses involving high numbers of both pro-inflammatory macrophages and multinucleated giant cells (MNGCs). In conclusion, this study delved into the repercussions of therapeutic ion doping on bone regeneration patterns and inflammatory responses, offering insights for the advancement of a new generation of biphasic calcium phosphate materials with potential clinical applicability.

An Elastin-Derived Composite Matrix for Enhanced Vascularized and Innervated Bone Tissue Reconstruction: From Material Development to Preclinical Evaluation.

Despite progress in bone tissue engineering, reconstruction of large bone defects remains an important clinical challenge. Here, a biomaterial designed to recruit bone cells, endothelial cells, and neuronal fibers within the same matrix is developed, enabling bone tissue regeneration. The bioactive matrix is based on modified elastin-like polypeptides (ELPs) grafted with laminin-derived adhesion peptides IKVAV and YIGSR, and the SNA15 peptide for retention of hydroxyapatite (HA) particles. The composite matrix shows suitable porosity, interconnectivity, biocompatibility for endothelial cells, and the ability to support neurites outgrowth by sensory neurons. Subcutaneous implantation leads to the formation of osteoid tissue, characterized by the presence of bone cells, vascular networks, and neuronal structures, while minimizing inflammation. Using a rat femoral condyle defect model, longitudinal micro-CT analysis is performed, which demonstrates a significant increase in the volume of mineralized tissue when using the ELP-based matrix compared to empty defects and a commercially available control (Collapat). Furthermore, visible blood vessel networks and nerve fibers are observed within the lesions after a period of two weeks. By incorporating multiple key components that support cell growth, mineralization, and tissue integration, this ELP-based composite matrix provides a holistic and versatile solution to enhance bone tissue regeneration.

Mg-Cross-Linked Alginate Hydrogel Induces BMSC/Macrophage Crosstalk to Enhance Bone Tissue Regeneration via Dual Promotion of the Ligand-Receptor Pairing of the OSM/miR-370-3p-gp130 Signaling Pathway.

Macrophages play a pivotal role in the crosstalk between the immune and skeletal systems, while Mg-based biomaterials demonstrate immunomodulatory capabilities in this procedure. However, the mechanism of how Mg2+ promotes osteogenesis through the interplay of bone marrow-derived mesenchymal stem cells (BMSCs) and macrophages remains undescribed. Here, we demonstrated that a Mg-cross-linked alginate hydrogel exerted a dual enhancement of BMSCs osteogenic differentiation through the ligand-receptor pairing of the OSM/miR-370-3p-gp130 axis. On the one hand, Mg2+, released from the Mg-cross-linked hydrogel, stimulates bone marrow-derived macrophages to produce and secrete more OSM. On the other hand, Mg2+ lowers the miR-370-3p level in BMSCs and in turn, reverses its suppression on gp130. Then, the OSM binds to the gp130 heterodimer receptor and activates intracellular osteogenic programs in BMSCs. Taken together, this study reveals a novel cross-talk pattern between the skeletal and immune systems under Mg2+ stimulation. This study not only brings new insights into the immunomodulatory properties of Mg-based biomaterials for orthopedic applications but also enriches the miRNA regulatory network and provides a promising target to facilitate bone regeneration in large bone defects.

Polydopamine-mediated immobilization of BMP-2 onto electrospun nanofibers enhances bone regeneration

Dealing with bone defects is a significant challenge to global health. Electrospinning in bone tissue engineering has emerged as a solution to this problem. In this study, we designed a PVDF-b-PTFE block copolymer by incorporating TFE, which induced a phase shift in PVDF from α to β, thereby enhancing the piezoelectric effect. Utilizing the electrospinning process, we not only converted the material into a film with a significant surface area and high porosity but also intensified the piezoelectric effect. Then we used polydopamine to immobilize BMP-2 onto PVDF-b-PTFE electrospun nanofibrous membranes, achieving a controlled release of BMP-2. The scaffold’s characters were examined using SEM and XRD. To assess its osteogenic effects in vitro, we monitored the proliferation of MC3T3-E1 cells on the fibers, conducted ARS staining, and measured the expression of osteogenic genes. In vivo, bone regeneration effects were analyzed through micro-CT scanning and HE staining. ELISA assays confirmed that the sustained release of BMP-2 can be maintained for at least 28 d. SEM images and CCK-8 results demonstrated enhanced cell viability and improved adhesion in the experimental group. Furthermore, the experimental group exhibited more calcium nodules and higher expression levels of osteogenic genes, including COL-I, OCN, and RUNX2. HE staining and micro-CT scans revealed enhanced bone tissue regeneration in the defective area of the PDB group. Through extensive experimentation, we evaluated the scaffold’s effectiveness in augmenting osteoblast proliferation and differentiation. This study emphasized the potential of piezoelectric PVDF-b-PTFE nanofibrous membranes with controlled BMP-2 release as a promising approach for bone tissue engineering, providing a viable solution for addressing bone defects.

Hydroxypropyl methylcellulose/sodium alginate/hydroxyapatite nano biomaterial enriched with zinc to promote bone tissue augmentation

Bone is a dynamic connective tissue that provides structural support and locomotion to human physiology. Severe bone degeneration can occur in cases of trauma, infections, genetic disorders, tumors, and hormonal imbalances. This leads to a demand for scaffolds and composites to enhance bone tissue regeneration. The present study aimed to develop a composite material using hydroxypropyl methylcellulose and sodium alginate in combination with hydroxyapatite. The composite was doped with zinc and developed into a nanocomposite using ionic gelation and solvent precipitation methods. The prepared nanocomposite was characterized by scanning electron microscopy, atomic force microscopy, dynamic light scattering, FTIR, and XRD studies. In vivo pharmacological studies were conducted to establish the bone targeting and bone tissue regeneration efficacy of the developed nanocomposite. The nanocomposite was checked for cell toxicity by performing an MTT assay using MG63 cell line and the molecular mechanism of targeting efficiency was assessed by an in silico evaluation method. The results of the study confirmed the polymeric interlinking in the nanocomposite and the successful preparation of a composite material using biodegradable excipients. SEM and AFM studies indicated that the nanocomposite was within the 80–200 nm size range. MTT assay indicated that the developed nanocomposite was not cytotoxic and well tolerated by the MG63 cell line. In vivo, studies in validation with molecular docking evaluation suggested that the nanocomposite was effectively targeted to the bone and enhanced the bone density by blocking Farnesyl Diphosphate Synthetase (FDPS) in the mevalonate pathway which is essential for inhibiting the osteoclastic activity and promoting osteogenesis.

Injectable Nanocomposite Hydrogels with Strong Antibacterial, Osteoinductive, and ROS-Scavenging Capabilities for Periodontitis Treatment.

Injectable antibacterial and osteoinductive hydrogels have received considerable attention for promoting bone regeneration owing to their versatile functionalities. However, a current hydrogel with antibacterial, osteoinductive, and antioxidant properties by a facile method for periodontitis treatment is still missing. To overcome this issue, we designed an injectable hydrogel system (GPM) composed of gelatin, Ti3C2Tx MXene nanosheets, and poly-l-lysine using a simple enzymatic cross-linking technique. Physicochemical characterization demonstrated that the GPM hydrogel matrix exhibited excellent stability, moderate tissue adhesion ability, and good mechanical behavior. The GPM hydrogels significantly inhibited the growth of Porphyromonas gingivalis, scavenged reactive oxygen species, attenuated inflammatory responses, and enhanced bone tissue regeneration. Intriguingly, the arrangement of the junctional epithelium, alveolar bone volume, and alveolar bone height in the GPM-treated periodontal disease group recovered to that of the healthy group. Therefore, our injectable hydrogel system with versatile functions may serve as an excellent tissue scaffold for the treatment of periodontitis.

Femtosecond laser ablation of 3D-printed PCL Scaffolds as a strategy to enhance bone tissue regeneration efficacy

New photonic techniques need to be developed to improve personalised medicine methods in tissue engineering. In the case of severe bone injuries, difficulties arise when creating platforms where cells required to be efficiently adhered. Femtosecond laser ablation appears as a versatile technique for modifying the surface of materials with high precision and neat outcomes. Thus, a strategy combining 3D printing of biopolymeric scaffolds and femtosecond laser ablation is proposed to design a device with enhanced material properties in terms of cell growth for bone tissue regeneration. Three different patterns were proposed, and it was proven that cell adhesion improvements rely on the pattern profile, assessing that grooved scaffold successfully increased cell adhesion and proliferation in comparison with micropitted samples.

Double-Network DNA Macroporous Hydrogel Enables Aptamer-Directed Cell Recruitment to Accelerate Bone Healing.

Recruiting endogenous bone marrow mesenchymal stem cells (BMSCs) in vivo to bone defect sites shows great promise in cell therapies for bone tissue engineering, which tackles the shortcomings of delivering exogenous stem cells, including limited sources, low retention, stemness loss, and immunogenicity. However, it remains challenging to efficiently recruit stem cells while simultaneously directing cell differentiation in the dynamic microenvironment and promoting neo-regenerated tissue ingrowth to achieve augmented bone regeneration. Herein, a synthetic macroporous double-network hydrogel presenting nucleic acid aptamer and nano-inducer enhances BMSCs recruitment, and osteogenic differentiation is demonstrated. An air-in-water template enables the rapid construction of highly interconnective macroporous structures, and the physical self-assembly of DNA strands and chemical cross-linking of gelatin chains synergistically generate a resilient double network. The aptamer Apt19S and black phosphorus nanosheets-specific macroporous hydrogel demonstrate highly efficient endogenous BMSCs recruitment, cell differentiation, and extracellular matrix mineralization. Notably, the enhanced calvarial bone healing with promising matrix mineralization and new bone formation is accompanied by adapting this engineered hydrogel to the bone defects. The findings suggest an appealing material approach overcoming the traditional limitations of cell-delivery therapy that can inspire the future design of next-generation hydrogel for enhanced bone tissue regeneration.

Hierarchically structured phycocyanin-loaded micro/nanofibrous membrane for guided bone regeneration

Although bone tissues possess an excellent inherent repair capacity, the ability to repair bone defects associated with osteoporosis, osteosarcoma, and congenital anomalies remains challenging. Several previous studies have developed biomaterials such as hydrogels, three-dimensional (3D) scaffolds, and nanofibrous scaffolds using synthetic and natural biomaterials that can deliver bioactive natural products to accelerate bone repair. Here, we evaluated the cytotoxicity, alkaline phosphatase activity, and mineral deposition capacity of MC3T3-E1 cells treated with Spirulina maxima-derived phycocyanin (PC), as well as the effects of PC on the expression of osteogenic protein markers such as osteocalcin and osteopontin in MC3T3-E1 cells. Next, we fabricated a PC-loaded poly lactic acid (PLA) and sodium alginate (SA) micro/nanofibrous membrane using emulsion electrospinning technology and generated hierarchically structured membranes using atelocollagen (AC) isolated from Paralichthys olivaceus. The microstructural architecture and physicochemical properties of the fabricated fibrous membranes were evaluated via scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), and water contact angle analyses. The fabricated hierarchically structured micro/nanofibrous membrane exhibited excellent in vitro biocompatibility, cytoskeleton organization, and mineral deposition. The fibrous membranes implanted into calvarial bone defect models were evaluated 12 weeks after surgery using micro-CT and histological analysis and the results confirmed that the implant could significantly enhance bone tissue regeneration. Overall, our findings confirmed that PC loaded hierarchically arranged micro/nanofibrous membranes have significant potential for bone tissue regeneration applications.

Enhancing bone tissue regeneration with rGO-coated Si-Ca-P bioceramic scaffold

Ceramic-based bone graft substitutes have been extensively studied for bone tissue engineering, due to their biocompatibility and osteoconductivity. Additionally, several studies have shown how graphene and its derivatives, due to their unique properties, can strongly promote cell adhesion, by enhance cellular adherence, proliferation, and osteoblast differentiation, and how graphene-based materials can promote spontaneous osteoblastic differentiation. The aim of this study was the use of a calcium silicophosphate ceramic, previously prepared in our laboratory, that presents excellent in vitro bioactivity, optimizing its operation by rGO coating. After coating with rGO any significant differences were observed in diffraction peaks from starting calcium silicophosphate ceramic, and SEM analysis showed a rough and undulating surface that favored a high specific surface area for promoting cell adhesion, proliferation and differentiation of cells. It could be confirmed by in vitro cell cultured with ahMSCs, showing adhesion and growing for cells with interconnected filaments extending over the surface, covering it after 7 days.

Coating of manganese functional polyetheretherketone implants for osseous interface integration.

Polyetheretherketone (PEEK) has been used extensively in biomedical engineering and it is highly desirable for PEEK implant to possess the ability to promote cell growth and significant osteogenic properties and consequently stimulate bone regeneration. In this study, a manganese modified PEEK implant (PEEK-PDA-Mn) was fabricated via polydopamine chemical treatment. The results showed that manganese was successfully immobilized on PEEK surface, and the surface roughness and hydrophilicity significantly improved after surface modification. Cell experiments in vitro demonstrated that the PEEK-PDA-Mn possesses superior cytocompatibility in cell adhesion and spread. Moreover, the osteogenic properties of PEEK-PDA-Mn were proved by the increased expression of osteogenic genes, alkaline phosphatase (ALP), and mineralization in vitro. Further rat femoral condyle defect model was utilized to assess bone formation ability of different PEEK implants in vivo. The results revealed that the PEEK-PDA-Mn group promoted bone tissue regeneration in defect area. Taken together, the simple immersing method can modify the surface of PEEK, giving outstanding biocompatibility and enhanced bone tissue regeneration ability to the modified PEEK, which could be applied as an orthopedic implant in clinical.

Strontium‐doped mesoporous silica nanoparticles incorporated in chitosan/alginate biocomposite scaffolds for enhanced bone tissue regeneration

AbstractCritical‐sized bone damage resulting from traumas, fractures, and tumors, impairs the bone tissues' inherent capacity for self‐repair. Conventional therapies could be associated with infection and pain besides demanding additional surgery while being costly. These limitations highlight the paucity of potential unique treatment strategies such as bone tissue engineering. In this study, strontium‐doped mesoporous silica nanoparticles (Sr‐MSN) were successfully synthesized and incorporated into the chitosan/alginate scaffolds which were then freeze‐dried and cross‐linked using CaCl2. The physicochemical characteristics of the fabricated scaffolds containing various Sr‐MSN contents were investigated using Fourier‐transform infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Energy Dispersive Spectroscopy (EDS). The hydrolytic degradation of the scaffolds was decreased with the increase in the Sr‐MSN content while maintaining their water uptake capacity. All fabricated scaffolds showed biocompatibility and Sr‐MSN‐containing scaffolds showed significantly increased Bone marrow mesenchymal stem cells (BMSCs) cell viability compared to chitosan/alginate scaffold after 72 h. The osteogenic differentiation potential investigations via mineralization assay and alkaline phosphatase enzyme activity indicated that the chitosan/alginate scaffold containing 20% Sr‐MSN showed the highest osteogenic differentiation capacity. Overall, bionanocomposite Cs/Alg/Sr‐MSN scaffolds integrated with desired physicochemical characteristics, biocompatibility, osteogenic differentiation capacity, and drug delivery potential show promising properties for attaining ideal results for bone repair and regeneration applications.

Composite bone-implant engineered with magnesium and variable degradation for orthopaedics

Metallic biomaterials are suitable for load-bearing scaffolds, and magnesium (Mg) alloy is the most preferable because of its mechanical properties are comparable to those of hard tissue (bone). The most important characteristic of an implant is its biocompatibility and Mg fully satisfies this standard. Mg is also biodegradable, thereby avoiding the need for secondary surgery. An uncontrollable degradation rate is one of the most significant limitations of magnesium-based implants, which hinders their applications in bone tissue engineering. Hydroxyapatite (HAP), a bioactive material, was incorporated into a magnesium metal matrix as a catalyst for enhancing bone tissue regeneration. Porosity in the scaffold could serve as a conduit for nutrients and also aids in the scaffold's weight reduction. This study investigated the effect of selective alloying elements (Ca, Zn, and Fe) on the biodegradability of scaffolds. Powder metallurgy was used to produce the magnesium alloy scaffolds. A calculated quantity of porogen particles, carbamide (urea), was incorporated into the Mg-Ca-Zn-Fe matrix in order to achieve 30% and 50% porosity. Due to the formation of Mg-Ca-Zn-Fe intermetallic compounds, the current study establishes that Mg alloy-based samples exhibit favorable biodegradation behavior. After seven days of immersion, the pH of the immersion liquid had also been found to have stabilized. Consequently, the observations suggest that the biodegradation behavior of bone implants could be modified by developing composite porous magnesium alloy implants.

Enhanced bone tissue regeneration using a 3D-printed poly(lactic acid)/Ti6Al4V composite scaffold with plasma treatment modification

The mechanical and biological properties of polylactic acid (PLA) need to be further improved in order to be used for bone tissue engineering (BTE). Utilizing a material extrusion technique, three-dimensional (3D) PLA-Ti6Al4V (Ti64) scaffolds with open pores and interconnected channels were successfully fabricated. In spite of the fact that the glass transition temperature of PLA increased with the addition of Ti64, the melting and crystallization temperatures as well as the thermal stability of filaments decreased slightly. However, the addition of 3–6 wt% Ti64 enhanced the mechanical properties of PLA, increasing the ultimate compressive strength and compressive modulus of PLA-3Ti64 to 49.9 MPa and 1.9 GPa, respectively. Additionally, the flowability evaluations revealed that all composite filaments met the print requirements. During the plasma treatment of scaffolds, not only was the root-mean-square (Rq) of PLA (1.8 nm) increased to 60 nm, but also its contact angle (90.4°) significantly decreased to (46.9°). FTIR analysis confirmed the higher hydrophilicity as oxygen-containing groups became more intense. By virtue of the outstanding role of plasma treatment as well as Ti64 addition, a marked improvement was observed in Wharton's jelly mesenchymal stem cell attachment, proliferation (4′,6-diamidino-2-phenylindole staining), and differentiation (Alkaline phosphatase and Alizarin Red S staining). Based on these results, it appears that the fabricated scaffolds have potential applications in BTE.

A Novel Chitosan Composite Biomaterial with Drug Eluting Capacity for Maxillary Bone Regeneration.

Bone grafting is one of the most commonly performed treatments for bone healing or repair. Autografts, grafts from the same patient, are the most frequently used bone grafts because they can provide osteogenic cells and growth factors at the site of the implant with reduced risk of rejection or transfer of diseases. Nevertheless, this type of graft presents some drawbacks, such as pain, risk of infection, and limited availability. For this reason, synthetic bone grafts are among the main proposals in regenerative medicine. This branch of medicine is based on the development of new biomaterials with the goal of increasing bone healing capacity and, more specifically in dentistry, they aim at simultaneously preventing or eliminating bacterial infections. The use of fibers made of chitosan (CS) and hydroxyapatite (HA) loaded with an antibiotic (doxycycline, DX) and fabricated with the help of an injection pump is presented as a new strategy for improving maxillary bone regeneration. In vitro characterization of the DX controlled released from the fibers was quantified after mixing different amounts of HA (10-75%). The 1% CS concentration was stable, easy to manipulate and exhibited adequate cuttability and pH parameters. The hydroxyapatite concentration dictated the combined fast and controlled release profile of CSHA50DX. Our findings demonstrate that the CS-HA-DX complex may be a promising candidate graft material for enhancing bone tissue regeneration in dental clinical practice.