Biomaterials For Bone Regeneration Research Articles

Poly(ester amide)-Bioactive Glass Hybrid Biomaterials for Bone Regeneration and Biomolecule Delivery.

Designing bioactive materials for repairing or regenerating bone defects is an active area of research and discovery. Despite advances made in sol-gel-derived hybrid biomaterials design, three challenges remain: (i) the choice of biodegradable polymers that can form a homogeneous solution in the presence of water is very limited, (ii) low-temperature (below 50 °C) incorporation of calcium into the inorganic matrix while having molecular-level mixing has proven to be a difficult task, and (iii) incorporation of drug-loaded mesoporous nanoparticles into polymer-bioactive glass hybrid scaffolds has not been achieved. In this study, we developed bioactive biomaterials for bone repair/regeneration from an α-amino acid-derived biodegradable poly(ester amide) (PEA) and a tertiary bioglass (SiO2-CaO-P2O5), where calcium was incorporated into the glass network at ambient temperature. Furthermore, drug-loaded functional mesoporous silica nanoparticles prepared by surfactant templating were successfully incorporated into PEA-bioglass porous scaffolds. The resulting homogenous single-phase materials showed deposition of hydroxyapatite on their surfaces, supported mesenchymal stem cell attachment and proliferation, and showed a sustained and slow release of a model compound. Taken together, these biomaterials have the potential to be used as a bifunctional platform for bone regeneration via ion release and biomolecule delivery.

Ex vivo investigations on bioinspired electrospun membranes as potential biomaterials for bone regeneration

ObjectivesTo assess the surface characteristics and composition that may enhance osteoblasts viability on novel electrospun composite membranes (organic polymer/silicon dioxide nanoparticles). MethodsMembranes are composed by a novel polymer blend, the mixture of two hydrophilic copolymers 2-hydroxyethylmethacrylate-co-methylmethacrylate and 2-hydroxyethylacrylate-co-methylacrylate, and they are doped with silicon dioxide nanoparticles. Then the membranes were functionalized with zinc or doxycycline. The membranes were morphologically characterized by atomic force and scanning electron microscopy (FESEM), and mechanically probed using a nanoindenter. Biomimetic calcium phosphate precipitation on polymeric tissues was assessed. Cell viability tests were performed using human osteosarcoma cells. Cells morphology was also studied by FESEM. Data were analyzed by ANOVA, Student-Newman-Keuls and Student t tests (p < 0.05). ResultsSilica doping of membranes enhanced bioactivity and increased mechanical properties. Membranes morphology and mechanical properties were similar to those of trabecular bone. Zinc and doxycycline doping did not exert changes but it increased novel membranes bioactivity. Membranes were found to permit osteoblasts proliferation. Silica-doping favored cells proliferation and spreading. As soon as 24 h after the seeding, cells in silica-doped membranes were firmly attached to experimental tissues trough filopodia, connected to each other. The cells produced collagen and minerals onto the surfaces. ConclusionsSilica nanoparticles enhanced surface properties and osteoblasts viability on electrospun membranes. Clinical significanceThe ability of silica-doped matrices to promote precipitation of calcium phosphate, together with their mechanical properties, observed non-toxicity, stimulating effect on osteoblasts and its surface chemistry allowing covalent binding of proteins, offer a potential strategy for bone regeneration applications.

Controlled release of basic fibroblast growth factor from a peptide biomaterial for bone regeneration.

Self-assembled peptide scaffolds based on D-RADA16 are an important matrix for controlled drug release and three-dimensional cell culture. In this work, D-RADA16 peptide hydrogels were coated on artificial bone composed of nano-hydroxyapatite/polyamide 66 (nHA/PA66) to obtain a porous drug-releasing structure for treating bone defects. The developed materials were characterized via transmission electron microscopy and scanning electron microscopy. The proliferation and adhesion of bone mesenchymal stem cells (BMSCs) were examined by confocal laser microscopy and CCK-8 experiments. The osteogenic ability of the porous materials towards bone BMSCs was examined in vitro by staining with Alizarin Red S and alkaline phosphatase, and bioactivity was evaluated in vivo. The results revealed that nHA/PA66/D-RADA16/bFGF reduces the degradation rate of D-RADA16 hydrogels and prolongs sustained release of bFGF, which would promote BMSCs proliferation, adhesion and osteogenesis in vitro and bone repair in vivo. Thus, it deserves more attention and is worthy of further research.

Functional Biomaterials for Bone Regeneration: A Lesson in Complex Biology

AbstractBone is a hard yet dynamic tissue with remarkable healing capacities. Research to date has greatly advanced the understanding of how bone heals and has led to marked success in the treatment of bone injuries. Nevertheless, the effective treatment of nonunions and large bone defects continues to present a challenge for orthopedic surgeons. Biomaterials provide researchers with a powerful instrument to potentially guide effective bone tissue regeneration in challenging healing environments. However, the most appropriate biomaterial for bone tissue engineering continues to be an area of intense debate. Indeed, the mechanical properties of real bone can be reproduced in vitro but the development of a functional bone substitute goes beyond the sole mechanical properties. The faithful reproduction of bone as a functional organ requires the combination of different cell types and temporal regulation of the molecular signaling involved during the different stages of bone formation and regeneration. This is not at all a trivial task. Herein, critical aspects of bone healing/regeneration including mechanical loading, inflammation, vascularization, and innervation are described. The success and the challenges behind the development of biomaterials, and the technologies used to functionalize them, in order to support the underlying cellular mechanisms are also highlighted.

Bioinspired Biomaterials with a Brick-and-Mortar Microstructure Combining Mechanical and Biological Performance.

The fabrication of bone regeneration biomaterials, which simultaneously possess superior mechanical performances and excellent bioactivity, remains challenging because these properties are usually mutually exclusive. Herein, inspired by the brick-and-mortar architecture of nacre, lamellar silicate-based bioceramic composites are successfully prepared by constructing orderly layered bioceramics infiltrated with a biomedical resin interlayer via the bidirectional freezing technique. The lamellar composites possess high strength and proper Young's moduli, which match with human cortical bone. Furthermore, the lamellar composites can release bioactive ions with a controlled profile, which significantly enhance the cell proliferation of both rabbit bone mesenchymal stem cells and periodontal ligament cells in vitro. Moreover, with the degradation of silicate bioceramics in vivo, newly formed bone tissue can grow into the materials to present the bioceramic/new bone/resin sandwich-like lamellar microstructure. The silicate-based bioceramic composites with brick-and-mortar architecture represent an excellent biomaterial in combination of superior mechanical performances matching that of human cortical bone, and excellent bioactivity for potential load-bearing bone regeneration.

RGD-functionalized supported lipid bilayers modulate pre-osteoblast adherence and promote osteogenic differentiation.

Biomaterial integration into bone requires optimal surface conditions to promote osteoprogenitor behavior, which is affected by integrin-binding via arginine-glycine-aspartate (RGD). RGD-functionalized supported lipid bilayers (SLBs) might be interesting as biomaterial coating in bone regeneration, because they allow integration of proteins, for example, growth factors, cytokines, and/or antibacterial agents. Since it is unknown whether and how they affect osteoprogenitor adhesion and differentiation, the aim was to investigate adhesion, focal adhesion formation, morphology, proliferation, and osteogenic potential of pre-osteoblasts cultured on RGD-functionalized SLBs compared to unfunctionalized SLBs and poly-l-lysine (PLL). After 17 hr, pre-osteoblast density on SLBs without or with RGD was similar, but lower than on PLL. Cell surface area, elongation, and number and size of phospho-paxillin clusters were also similar. Cells on SLBs without or with RGD were smaller, more elongated, and had less and smaller phospho-paxillin clusters than on PLL. OPN expression was increased on SLBs with RGD compared to PLL. Moreover, after 1 week, COL1a1 expression was increased on SLBs without or with RGD. In conclusion, pre-osteoblast adhesion and enhanced differentiation were realized for the first time on RGD-functionalized SLBs, pointing to a new horizon in the management of bone regeneration using biomaterials. Together with SLBs nonfouling nature and the possibility of adjusting SLB fluidity and peptide content make SLBs highly promising as substrate to develop innovative biomimetic coatings for biomaterials in bone regeneration.

Exploratory Full-Field Strain Analysis of Regenerated Bone Tissue from Osteoinductive Biomaterials.

Biomaterials for bone regeneration are constantly under development, and their application in critical-sized defects represents a promising alternative to bone grafting techniques. However, the ability of all these materials to produce bone mechanically comparable with the native tissue remains unclear. This study aims to explore the full-field strain evolution in newly formed bone tissue produced in vivo by different osteoinductive strategies, including delivery systems for BMP-2 release. In situ high-resolution X-ray micro-computed tomography (microCT) and digital volume correlation (DVC) were used to qualitatively assess the micromechanics of regenerated bone tissue. Local strain in the tissue was evaluated in relation to the different bone morphometry and mineralization for specimens (n = 2 p/treatment) retrieved at a single time point (10 weeks in vivo). Results indicated a variety of load-transfer ability for the different treatments, highlighting the mechanical adaptation of bone structure in the early stages of bone healing. Although exploratory due to the limited sample size, the findings and analysis reported herein suggest how the combination of microCT and DVC can provide enhanced understanding of the micromechanics of newly formed bone produced in vivo, with the potential to inform further development of novel bone regeneration approaches.

Modulating the cobalt dose range to manipulate multisystem cooperation in bone environment: a strategy to resolve the controversies about cobalt use for orthopedic applications.

The paradoxical effect of cobalt on biological processes has aroused controversy regarding the application of cobalt-based biomaterials in bone regeneration. Tuning the dose range of cobalt ions may be a valid strategy to resolve the controversies about cobalt use for orthopedic applications. Recent progress in bone biology has highlighted the effects of multisystem cooperation (especially of osteoimmune, skeletal, and vascular systems) on bone dynamics. Before the application of this dose-tuning strategy, a deeper understanding of its dose-dependent effect on the cooperation of osteoimmune, skeletal, and vascular systems is needed. However, due to the difficulties with investigating the interaction of multiple systems in vitro, the multimodal effects of cobalt on bone homeostasis were investigated here, in an in vivo scenario.Methods: In vitro CCK8 assay and cytoskeletal staining were preformed to detecte the cell cytotoxic reaction in response to 0.1-100 ppm cobalt stimulation. Blood clot containing 0.1 to 5 ppm of cobalt were implanted in the rat calvarium defect. The gene profile of osteoimmune, skeletal, and vascular system as well as the systemic toxicity were evaluated via RT-qPCR, histological analysis and inductively coupled plasma mass spectrometry. The bone regeneration, osteoclastogenesis and vascularization were assessed by micro-ct and histological analysis.Results: Cobalt concentration below 5 ppm did not cause cell toxicity in vitro. No systemic toxicity was observed in vivo at 0.1-5 ppm cobalt concentration. It was found that the early cytokine profiles of the multiple interacting systems were different in response to different cobalt doses. Most of the anti-inflammatory, osteogenic, and proangiogenic factors were upregulated in the 1 ppm cobalt group at the early stage. In the late stage, the 1ppm group was most superior in bone regenerative effect while the 5 ppm group displayed the strongest osteoclastogenesis activity.Conclusions: The 1 ppm concentration of cobalt yielded the most favorable cooperation of the osteoimmune, skeletal, and vascular systems and subsequently optimal bone regeneration outcomes. Tuning the cobalt dose range to manipulate the cooperation of osteoimmune, skeletal, and vascular systems could be a promising and valuable strategy to prevent paradoxical effects of cobalt while preserving its beneficial effects.

The Development of Extracellular Vesicle-Integrated Biomaterials for Bone Regeneration.

The clinical need for effective bone regeneration remains in huge demands. Although autologous and allogeneic bone grafts are generally considered "gold standard" treatments for bone defects, these approaches may result in various complications. Furthermore, safety considerations of gene- and cell-based therapies require further clarification and approval from regulatory authorities. Therefore, developing new therapeutic biomaterials that can empower endogenous regenerative properties to accelerate bone repair and regeneration is of great significance. Extracellular vesicles (EVs) comprise a heterogeneous population of naturally derived nanoparticles that play a critical role in mediating cell-cell communication. The vast amount of biological processes that EVs are involved in, such as immune modulation, senescence, and angiogenesis, and the versatility of manner in which they can influence the behavior of recipient cells make EVs an interesting source for both diagnostic and therapeutic applications. Advancement of knowledge in the fields of immunology and cell biology has sparked the exploration of the potential of EVs in the field of regenerative medicine. EVs travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating the recruitment, proliferation, and differentiation of recipient cells. Numerous studies have demonstrated the pivotal role of EVs in tissue regeneration both in vitro and in vivo. In this chapter, we will outline current knowledge surrounding EVs, summarize their functional roles in bone regenerative medicine, and elaborate on potential application and challenges of EV-integrated biomaterials in bone tissue engineering.

Functionalization of Silk Fibers by PDGF and Bioceramics for Bone Tissue Regeneration

Bone regeneration is a complex, well-organized physiological process of bone formation observed during normal fracture healing and involved in continuous remodeling throughout adult life. An ideal medical device for bone regeneration requires interconnected pores within the device to allow for penetration of blood vessels and cells, enabling material biodegradation and bone ingrowth. Additional mandatory characteristics include an excellent resorption rate, a 3D structure similar to natural bone, biocompatibility, and customizability to multiple patient-specific geometries combined with adequate mechanical strength. Therefore, endless silk fibers were spun from native silk solution isolated from silkworm larvae and functionalized with osteoconductive bioceramic materials. In addition, transgenic silkworms were generated to functionalize silk proteins with human platelet-derived growth factor (hPDGF). Both, PDGF-silk and bioceramic modified silk were then assembled into 3D textile implants using an additive manufacturing approach. Textile implants were characterized in terms of porosity, compressive strength, and cyclic load. In addition, osteogenic differentiation of mesenchymal stem cells was evaluated. Silk fiber-based 3D textile implants showed good cytocompatibility and stem cells cultured on bioceramic material functionalized silk implants were differentiating into bone cells. Thus, functionalized 3D interconnected porous textile scaffolds were shown to be promising biomaterials for bone regeneration.

A BMSCs-laden quercetin/duck's feet collagen/hydroxyapatite sponge for enhanced bone regeneration.

Treating critical-sized bone defects is an important issue in the field of tissue engineering and bone regeneration. From the various biomaterials for bone regeneration, collagen is an important and widely used biomaterial in biomedical applications, hence, it has numerous attractive properties including biocompatibility, hyper elastic behavior, prominent mechanical properties, support cell adhesion, proliferation, and biodegradability. In the present study, collagen was extracted from duck's feet (DC) as a new collagen source and combined with quercetin (Qtn), a type of flavonoids found in apple and onions and has been reported to affect the bone metabolism, for increasing osteogenic differentiation. Further, improving osteoconductive properties of the scaffold hydroxyapatite (HAp) a biodegradable material was used. We prepared 0, 25, 50, and 100 μM Qtn/DC/HAp sponges using Qtn, DC, and HAp. Their physiochemical characteristics were evaluated using scanning electron microscopy, compressive strength, porosity, and Fourier transform infrared spectroscopy. To assess the effect of Qtn on osteogenic differentiation, we cultured bone marrow mesenchymal stem cells on the sponges and evaluated by alkaline phosphatase, 3-4-2, 5-diphenyl tetrazolium bromide assay, and real-time polymerase chain reaction. Additionally, they were studied implanting in rat, analyzed through Micro-CT and histological staining. From our in vitro and in vivo results, we found that Qtn has an effect on bone regeneration. Among the different experimental groups, 25 μM Qtn/DC/HAp sponge was found to be highly increased in cell proliferation and osteogenic differentiation compared with other groups. Therefore, 25 μM Qtn/DC/HAp sponge can be used as an alternative biomaterial for bone regeneration in critical situations.

Crayfish hemocyanin on chitin bone substitute scaffolds promotes the proliferation and osteogenic differentiation of human mesenchymal stem cells.

Crustacean chitin-hemocyanin-calcium mineral complexes were designed as bone biomimetics, with emphasis on their ability to bind or release calcium ions. Chitin scaffolds were prepared by dissolving chitin flakes in LiCl/dimethylacetamide, followed by gel formation and freeze-drying. Some of these scaffolds were modified by incorporation of CaCO3 . In some of the chitin-CaCO3 scaffolds, macroporosity was introduced by HCl treatment. Hemocyanin from the crayfish Cherax quadricarinatus was used to further modify the chitin scaffolds by dip coating. Cytocompatibility, cellular adherence and proliferation of human mesenchymal stem cells (hMSCs) were evaluated in terms of cell number as reflected in lactate dehydrogenase activity. The chitin, chitin-CaCO3 , and porous chitin-CaCO3 scaffolds were all found to facilitate cell attachment. Hemocyanin dip-coating of these scaffolds led to increased initial cell adhesion, enhanced proliferation, and osteogenic differentiation. Since the hemocyanin loading of the scaffolds was impaired by sterilization by gamma-irradiation (as required for biomedical applications), the hemocyanin loading was performed on previously sterilized scaffolds. All scaffolds facilitated osteogenic differentiation of osteoblasts, with the highest cell ALP-activity being found on hemocyanin-modified porous chitin-CaCO3 scaffolds. Thus, chitin-hemocyanin scaffolds enhanced the initial stages of bone cell development and could serve as promising biomaterials for bone regeneration.

Formation of core-shell structured calcium silicate fiber via sol-gel electrospinning and controlled calcination

Ceramic nanofibers prepared via precursor sol-gel electrospinning and calcination are widely reported, but few reports address the possible formation of core-shell structured ceramic nanofibers. In this study, core-shell structured calcium silicate (CS) nanofibers were obtained by changing the compositions of the precursor sol-gel solutions and the calcination temperatures to determine the mechanism leading to the core-shell structure during preparation. The sol-gel solutions used to produce CS nanofibers were prepared from calcium nitrate and tetraethyl orthosilicate, and it was found that CS nanofibers prepared from sol-gel solutions with a Ca/Si molar ratio of less than 1:1 displayed a distinguishable core-shell structure with calcination temperatures higher than 1000 °C. The fiber shell was identified as mainly silica with sparse calcium, and the fiber core was composed predominantly of calcium silicate. A tubular morphology was clearly observed with preferential degradation of the fiber core. The fiber shell became thinner or it disappeared if the precursor sol-gel solutions had Ca/Si molar ratios higher than 1:1 or if the applied calcination temperature was less than 1000 °C. After doping the CS fibers with zinc, it was confirmed that the zinc was also predominantly located in the fiber core, similar to calcium. It was proposed that the formation of CS nanofibers with a surface silica layer resulted from the migration of Si-O-Si precursor gel particles toward the fiber surface with solvent evaporation during electrospinning and transformed into a silica shell during calcination. Thus, the calcium (or zinc) elements were enriched inside the fiber to obtain a type of heterogeneous CS nanofiber. These materials are expected to serve as good biomaterials for bone regeneration by providing sustained release of bioactive ions.

Gene activated adipose tissue fragments as advanced autologous biomaterials for bone regeneration: osteogenic differentiation within the tissue and implications for clinical translation

Cost-effective, expedited approaches for bone regeneration are urgently needed in an ageing population. Bone Morphogenetic Proteins (BMPs) stimulate osteogenesis but their efficacy is impeded by their short half-life. Delivery by genetically modified cells can overcome this problem. However, cell isolation and propagation represent significant obstacles for the translation into the clinic. Instead, complete gene activated fragments of adipose tissue hold great potential for bone repair. Here, using an in-vitro culture system, we investigated whether adenoviral transduction with human BMP-2 can promote osteogenic differentiation within adipose tissue fragments. Osteoinduction in adipose tissue fragments was evaluated by quantitative reverse transcriptase polymerase chain reaction, immunohistology and histomorphometry. BMP-2 transduced adipose tissue synthesized BMP-2 protein over 30 days peaking by day six, which significantly promoted osteogenic differentiation as indicated by increased calcium depositions, up-regulation of bone marker genes, and bone-related protein expression. Our results demonstrate that cells within adipose tissue fragments can differentiate osteogenically after BMP-2 transduction of cells on the surface of the adipose tissue. BMP-2 gene activated adipose tissue represents an advanced osteo-regenerative biomaterial that can actively contribute to osteogenesis and potentially enable the development of a novel, cost-effective, one-step surgical approach to bone repair without the need for cell isolation.

Collagen I-based scaffolds negatively impact fracture healing in a mouse-osteotomy-model although used routinely in research and clinical application

Although several biomaterials for bone regeneration have been developed in the last decades, clinical application of bone morphogenetic protein 2 is clinically only approved when applied on an absorbable bovine collagen I scaffold (ACS) (Helistat; ACS-H). In research, another ACS, namely Lyostypt (ACS-L) is frequently used as a scaffold in bone-linked studies. Nevertheless, until today, the influence of ACS alone on bone healing remains unknown. Unexpectedly, in vitro studies using ASC-H revealed a suppression of osteogenic differentiation and a significant reduction of cell vitality when compared to ASC-L. In mice, we observed a significant delay in bone healing when applying ACS-L in the fracture gap during femoral osteotomy. The results of our study show for the first time a negative influence of both ACS-H and ACS-L on bone formation demonstrating a substantial need for more sophisticated delivery systems for local stimulation of bone healing in both clinical application and research. Statement of SignificanceOur study provides evidence-based justification to promote the development and approval of more suitable and sophisticated delivery systems in bone healing research. Additionally, we stimulate researchers of the field to consider that the application of those scaffolds as a delivery system for new substances represents a delayed healing approach rather than a normal bone healing which could greatly impact the outcome of those studies and play a pivotal role in the translation to the clinics. Moreover, we provide impulses on underlying mechanism involving the roles of small-leucine rich proteoglycans (SLRP) for further detailed investigations.

Gelatin methacryloyl (GelMA)-based biomaterials for bone regeneration.

Gelatin methacryloyl (GelMA)-based biomaterials have been widely used in various biomedical applications due to their suitable biological properties and tuneable physical characteristics. In particular, GelMA can be used as a versatile matrix for bone tissue engineering scaffolds via various strategies to overcome major obstacles such as insufficient mechanical property and uncontrollable degradation. This review presents the research status of GelMA, its structure and function, GelMA-based biomaterials and the development of methods along with their existing challenges.

Current Advances in Immunomodulatory Biomaterials for Bone Regeneration.

Biomaterials with suitable surface modification strategies are contributing significantly to the rapid development of the field of bone tissue engineering. Despite these encouraging results, utilization of biomaterials is poorly translated to human clinical trials potentially due to lack of knowledge about the interaction between biomaterials and the body defense mechanism, the "immune system". The highly complex immune system involves the coordinated action of many immune cells that can produce various inflammatory and anti-inflammatory cytokines. Besides, bone fracture healing initiates with acute inflammation and may later transform to a regenerative or degenerative phase mainly due to the cross-talk between immune cells and other cells in the bone regeneration process. Among various immune cells, macrophages possess a significant role in the immune defense, where their polarization state plays a key role in the wound healing process. Growing evidence shows that the macrophage polarization state is highly sensitive to the biomaterial's physiochemical properties, and advances in biomaterial research now allow well controlled surface properties. This review provides an overview of biomaterial-mediated modulation of the immune response for regulating key bone regeneration events, such as osteogenesis, osteoclastogenesis, and inflammation, and it discusses how these strategies can be utilized for future bone tissue engineering applications.

Influence of photoinitiator concentration and irradiation time on the crosslinking performance of visible-light activated pullulan-HEMA hydrogels

In-situ forming hydrogels were prepared from pullulan-HEMA copolymer using three-component visible-light system composed of camphorquinone carboxylic acid-folic acid-iodonium salt. The relevance of double bond conversion and crosslinking density of hydrogels with the photoinitiator concentration and irradiation time were estimated by FT-IR analysis and swelling calculation using Flory-Rehner theory, respectively. The results revealed that the crosslinking density and degree of conversion of hydrogels were improved by photoinitiator concentration increasing until certain extend, then they decreased due to a primary radicals termination reaction occurred. The shortest irradiation time of 10 s was essential to obtain acceptable hydrogels for further characterizations. For the probability use of hydrogels as scaffold was investigated in vitro by measuring of the indirect cytotoxicity assay by MTT-assay using human bone Sarcoma cell as a reference cell lines. The majority of seeded SW1353 cells maintained a live with an accepted viability of ~85–92% over a four days culture period with irradiation of hydrogel 10 s, while cell viability has improved to ~95–98% with prolonging the irradiation time of hydrogel to 60 s. The current photoinitiating system is a proper system for in-situ crosslinking the activated-light biomaterials for bone regeneration, dental, or tissue engineering applications.

Additively manufactured biodegradable porous iron

Additively manufactured (AM) topologically ordered porous metallic biomaterials with the proper biodegradation profile offer a unique combination of properties ideal for bone regeneration. These include a fully interconnected porous structure, bone-mimicking mechanical properties, and the possibility of fully regenerating bony defects. Most of such biomaterials are, however, based on magnesium and, thus, degrade too fast. Here, we present the first report on topologically ordered porous iron made by Direct Metal Printing (DMP). The topological design was based on a repetitive diamond unit cell. We conducted a comprehensive study on the in vitro biodegradation behavior (up to 28 days), electrochemical performance, time-dependent mechanical properties, and biocompatibility of the scaffolds. The mechanical properties of AM porous iron (E = 1600–1800 MPa) were still within the range of the values reported for trabecular bone after 28 days of biodegradation. Electrochemical tests showed up to ≈12 times higher rates of biodegradation for AM porous iron as compared to that of cold-rolled (CR) iron, while only 3.1% of weight loss was measured after 4 weeks of immersion tests. The biodegradation mechanisms were found to be topology-dependent and different between the periphery and central parts of the scaffolds. While direct contact between MG-63 cells and scaffolds revealed substantial and almost instant cytotoxicity in static cell culture, as compared to Ti-6Al-4V, the cytocompatibility according to ISO 10993 was reasonable in in vitro assays for up to 72 h. This study shows how DMP could be used to increase the surface area and decrease the grain sizes of topologically ordered porous metallic biomaterials made from metals that are usually considered to degrade too slowly (e.g., iron), opening up many new opportunities for the development of biodegradable metallic biomaterials. Statement of SignificanceBiodegradation in general and proper biodegradation profile in particular are perhaps the most important requirements that additively manufactured (AM) topologically ordered porous metallic biomaterials should offer in order to become the ideal biomaterial for bone regeneration. Currently, most biodegradable metallic biomaterials are based on magnesium, which degrade fast with gas generation. Here, we present the first report on topologically ordered porous iron made by Direct Metal Printing (DMP). We also conducted a comprehensive study on the biodegradation behavior, electrochemical performance, biocompatibility, and the time evolution of the mechanical properties of the implants. We show that these implants possess bone-mimicking mechanical properties, accelerated degradation rate, and reasonable cytocompatibility, opening up many new opportunities for the development of iron-based biodegradable materials.

Biodegradable Multifunctional Bioactive Glass-Based Nanocomposite Elastomers with Controlled Biomineralization Activity, Real-Time Bioimaging Tracking, and Decreased Inflammatory Response.

Controlled biomineralization activity of biomaterials is rather important in bone regeneration and osseointegration avoiding the formation of fibrous capsule. However, most of conventional biodegradable elastomeric biomaterials for bone regeneration do not possess biomineralization ability and inherent multifunctional properties. Herein, we report a multifunctional bioactive glass (BG)-based hybrid poly(citrate-siloxane) (PCS) elastomer with intrinsical biomineralization activity and photoluminescent properties for potential bone tissue regeneration. Monodispersed BG nanoparticles (BGNs) were used to control the elastomeric behavior, biomineralization activity, photoluminescent ability, and osteogenic cellular response of PCS elastomers. BGNs significantly enhanced the elastomeric modulus of PCS from 20 to 200 MPa (10 times improvement) and the hydrophilicity (from 82° to 28° in water contact angle). The photoluminescent properties of PCS elastomers were also tailored through the incorporation of BGNs. The in vivo degradation of PCS-BGN nanocomposites could be efficiently tracked through noninvasively monitoring their fluorescent change. PCS-BGN nanocomposites enhanced the proliferation and osteoblastic differentiation of osteoblasts (MC3T3-E1) and decreased the in vivo inflammatory response. This study provided a novel tactics for designing the bioactive elastomeric biomaterials with multifunctional properties for bone regeneration medicine.