Effect of Laser Scan Speed on Defects and Texture Development of Pure Chromium Metal Fabricated via Powder Bed Fusion-Laser Beam.

Chromium (Cr) metal has garnered significant attention in alloy systems owing to its exceptional properties, such as a high melting point, low density, and superior oxidation and corrosion resistance. However, its processing capabilities are hindered by its high ductile-brittle transition temperature (DBTT). Recently, powder bed fusion-laser beam for metals (PBF-LB/M) has emerged as a promising technique, offering the fabrication of net shapes and precise control over crystallographic texture. Nevertheless, research investigating the mechanism underlying crystallographic texture development in pure Cr via PBF-LB/M still needs to be conducted. This study explored the impact of scan speed on relative density and crystallographic texture. At the optimal scan speed, an increase in grain size attributed to epitaxial growth was observed, resulting in the formation of a <100> cubic texture. Consequently, a reduction in high-angle grain boundaries (HAGB) was achieved, suppressing defects such as cracks and enhancing relative density up to 98.1%. Furthermore, with increasing densification, Vickers hardness also exhibited a corresponding increase. These findings underscore the efficacy of PBF-LB/M for processing metals with high DBTT properties.

Adaptive enhancement of apatite crystal orientation and Young's modulus under elevated load in rat ulnar cortical bone.

Functional adaptation refers to the active modification of bone structure according to the mechanical loads applied daily to maintain its mechanical integrity and adapt to the environment. Functional adaptation relates to bone mass, bone mineral density (BMD), and bone morphology (e.g., trabecular bone architecture). In this study, we discovered for the first time that another form of bone functional adaptation of a cortical bone involves a change in bone quality determined by the preferential orientation of apatite nano-crystallite, a key component of the bone. An in vivo rat ulnar axial loading model was adopted, to which a 3-15 N compressive load was applied, resulting in approximately 440-3200 µÉ› of compression in the bone surface. In the loaded ulnae, the degree of preferential apatite c-axis orientation along the ulnar long axis increased in a dose-dependent manner up to 13 N, whereas the increase in BMD was not dose-dependent. The Young's modulus along the same direction was enhanced as a function of the degree of apatite orientation. This finding indicates that bone has a mechanism that modifies the directionality (anisotropy) of its microstructure, strengthening itself specifically in the loaded direction. BMD, a scalar quantity, does not allow for load-direction-specific strengthening. Functional adaptation through changes in apatite orientation is an excellent strategy for bones to efficiently change their strength in response to external loading, which is mostly anisotropic.

Host bone microstructure for enhanced resistance to bacterial infections.

Postoperative bacterial infection is a serious complication of orthopedic surgery. Not only infections that develop in the first few weeks after surgery but also late infections that develop years after surgery are serious problems. However, the relationship between host bone and infection activation has not yet been explored. Here, we report a novel association between host bone collagen/apatite microstructure and bacterial infection. The bone-mimetic-oriented micro-organized matrix structure was obtained by prolonged controlled cell alignment using a grooved-structured biomedical titanium alloy. Surprisingly, we have discovered that highly aligned osteoblasts have a potent inhibitory effect on Escherichia coli adhesion. Additionally, the oriented collagen/apatite micro-organization of the bone matrix showed excellent antibacterial resistance against Escherichia coli. The proposed mechanism for realizing the antimicrobial activity of the micro-organized bone matrix is by the controlled secretion of the antimicrobial peptides, including ß-defensin 2 and ß-defensin 3, from the highly aligned osteoblasts. Our findings contribute to the development of anti-infective strategies for orthopedic surgeries. The recovery of the intrinsically ordered bone matrix organization provides superior antibacterial resistance after surgery.

Quantitative Threshold Determination of Auditory Brainstem Responses in Mouse Models.

The auditory brainstem response (ABR) is a scalp recording of potentials produced by sound stimulation, and is commonly used as an indicator of auditory function. However, the ABR threshold, which is the lowest audible sound pressure, cannot be objectively determined since it is determined visually using a measurer, and this has been a problem for several decades. Although various algorithms have been developed to objectively determine ABR thresholds, they remain lacking in terms of accuracy, efficiency, and convenience. Accordingly, we proposed an improved algorithm based on the mutual covariance at adjacent sound pressure levels. An ideal ABR waveform with clearly defined waves I-V was created; moreover, using this waveform as a standard template, the experimentally obtained ABR waveform was inspected for disturbances based on mutual covariance. The ABR testing was repeated if the value was below the established cross-covariance reference value. Our proposed method allowed more efficient objective determination of ABR thresholds and a smaller burden on experimental animals.

Novel nano-hydroxyapatite coating of additively manufactured three-dimensional porous implants improves bone ingrowth and initial fixation.

Electron beam melting (EBM) has been used to fabricate three-dimensional (3D) porous Ti-6Al-4V surfaces for acetabular cups in total hip arthroplasty. However, there are radiographic concerns regarding poor implant fixation and bone ingrowth around electron beam melted (EBMed) 3D porous cups. We hypothesize that nano-hydroxyapatite (nHA) coating can promote bone ingrowth and thus decrease the occurrence of radiolucent lines around EBMed 3D porous cups. This study aimed to investigate the effect of a novel nHA coating on the biological performance of EBMed 3D porous implants in a beagle transcortical model. Low-porosity (control) and high-porosity 3D porous Ti-6Al-4V implants were manufactured using EBM. Half of the high-porosity implants were coated with nHA without clogging the 3D pores. Implants were inserted into the femoral diaphysis of the beagles. The beagles were euthanized at 4, 8, and 12 weeks postoperatively, and push-out testing was performed. Bone ingrowth was evaluated by histological analysis. Although the increase in porosity alone had no effect on biological behavior, the addition of nHA to high-porosity 3D implants significantly improved early bone fixation and bone ingrowth into the deep region of porous structures compared to low-porosity implants. This is the first report of a novel nHA coating that improved bone ingrowth into the deeper regions of 3D porous implants, which can prevent the occurrence of radiolucent lines around EBMed 3D porous cups.

Innovative design of bone quality-targeted intervertebral spacer: accelerated functional fusion guiding oriented collagen and apatite microstructure without autologous bone graft.

BACKGROUND CONTEXT: Although autologous bone grafting is widely considered as an ideal source for interbody fusion, it still carries a risk of nonunion. The influence of the intervertebral device should not be overlooked. Requirements for artificial spinal devices are to join the vertebrae together and recover the original function of the spine rapidly. Ordered mineralization of apatite crystals on collagen accelerates bone functionalization during the healing process. Particularly, the stable spinal function requires the ingrowth of an ordered collagen and apatite matrix which mimics the intact intervertebral microstructure. This collagen and apatite ordering is imperative for functional bone regeneration, which has not been achieved using classical autologous grafting. PURPOSE: We developed an intervertebral body device to achieve high stability between the host bone and synthesized bone by controlling the ordered collagen and apatite microstructure. STUDY DESIGN: This was an in vivo animal study. METHODS: Intervertebral spacers with a through-pore grooved surface structure, referred to as a honeycomb tree structure, were produced using metal 3D printing. These spacers were implanted into normal sheep at the L2-L3 or L4-L5 disc levels. As a control group, grafting autologous bone was embedded. The mechanical integrity of the spacer/bone interface was evaluated through push-out tests. RESULTS: The spacer with honeycomb tree structure induced anisotropic trabecular bone growth with textured collagen and apatite orientation in the through-pore and groove directions. The push-out load of the spacer was significantly higher than that of the conventional autologous graft spacer. Moreover, the load was significantly correlated with the anisotropic texture of the newly formed bone matrix. CONCLUSIONS: The developed intervertebral spacer guided the regenerated bone matrix orientation of collagen and apatite, resulting in greater strength at the spacer/host bone interface than that obtained using a conventional gold-standard autologous bone graft. CLINICAL SIGNIFICANCE: Our results provide a foundation for designing future spacers for interbody fusion in human.

A Novel Ex Vivo Bone Culture Model for Regulation of Collagen/Apatite Preferential Orientation by Mechanical Loading.

The anisotropic microstructure of bone, composed of collagen fibers and biological apatite crystallites, is an important determinant of its mechanical properties. Recent studies have revealed that the preferential orientation of collagen/apatite composites is closely related to the direction and magnitude of in vivo principal stress. However, the mechanism of alteration in the collagen/apatite microstructure to adapt to the mechanical environment remains unclear. In this study, we established a novel ex vivo bone culture system using embryonic mouse femurs, which enabled artificial control of the mechanical environment. The mineralized femur length significantly increased following cultivation; uniaxial mechanical loading promoted chondrocyte hypertrophy in the growth plates of embryonic mouse femurs. Compressive mechanical loading using the ex vivo bone culture system induced a higher anisotropic microstructure than that observed in the unloaded femur. Osteocytes in the anisotropic bone microstructure were elongated and aligned along the long axis of the femur, which corresponded to the principal loading direction. The ex vivo uniaxial mechanical loading successfully induced the formation of an oriented collagen/apatite microstructure via osteocyte mechano-sensation in a manner quite similar to the in vivo environment.

Outstanding in vivo mechanical integrity of additively manufactured spinal cages with a novel "honeycomb tree structure" design via guiding bone matrix orientation.

BACKGROUND CONTEXT: Therapeutic devices for spinal disorders, such as spinal fusion cages, must be able to facilitate the maintenance and rapid recovery of spinal function. Therefore, it would be advantageous that future spinal fusion cages facilitate rapid recovery of spinal function without secondary surgery to harvest autologous bone. PURPOSE: This study investigated a novel spinal cage configuration that achieves in vivo mechanical integrity as a devise/bone complex by inducing bone that mimicked the sound trabecular bone, hierarchically and anisotropically structured trabeculae strengthened with a preferentially oriented extracellular matrix. STUDY DESIGN/SETTINGS: In vivo animal study. METHODS: A cage possessing an anisotropic through-pore with a grooved substrate, that we termed "honeycomb tree structure," was designed for guiding bone matrix orientation; it was manufactured using a laser beam powder bed fusion method through an additive manufacturing processes. The newly designed cages were implanted into sheep vertebral bodies for 8 and 16 weeks. An autologous bone was not installed in the newly designed cage. A pull-out test was performed to evaluate the mechanical integrity of the cage/bone interface. Additionally, the preferential orientation of bone matrix consisting of collagen and apatite was determined. RESULTS: The cage/host bone interface strength assessed by the maximum pull-out load for the novel cage without an autologous bone graft (3360±411 N) was significantly higher than that for the conventional cage using autologous bone (903±188 N) after only 8 weeks post-implantation. CONCLUSIONS: These results highlight the potential of this novel cage to achieve functional fusion between the cage and host bone. Our study provides insight into the design of highly functional spinal devices based on the anisotropic nature of bone. CLINICAL SIGNIFICANCE: The sheep spine is similar to the human spine in its stress condition and trabecular bone architecture and is widely recognized as a useful model for the human spine. The present design may be useful as a new spinal device for humans.

Combination treatment with ibandronate and eldecalcitol prevents osteoporotic bone loss and deterioration of bone quality characterized by nano-arrangement of the collagen/apatite in an ovariectomized aged rat model.

Combination therapy with bisphosphonates and vitamin D3 analogs has been frequently used for the treatment of osteoporosis. However, its effects on bone anisotropies, such as orientations of collagen and apatite at the nanometer-scale, which is a promising bone quality index, and its trabecular architecture at the micrometer scale, are not well understood despite its important mechanical properties and its role in fracture risk. In the present study, we analyzed the effects of ibandronate (IBN), eldecalcitol (ELD), and their combination on the collagen/apatite orientation and trabecular architectural anisotropy using an estrogen-deficiency-induced osteoporotic rat model. Estrogen deficiency caused by ovariectomy (OVX) excessively increased the degree of collagen/apatite orientation or trabecular architectural anisotropy along the craniocaudal axis in the lumbar vertebra compared to that of the sham-operated group. The craniocaudal axis corresponds to the direction of principal stress in the spine. The excessive material anisotropy in the craniocaudal axis contributed to the enhanced Young's modulus, which may compensate for the reduced mechanical resistance by bone loss to some extent. The solo administration of IBN and ELD prevented the reduction of bone fraction (BV/TV) determined by µ-CT, and combination therapy showed the highest efficacy in BV/TV gain. Furthermore, the solo administration and combination treatment significantly decreased the degree of collagen/apatite orientation to the sham level. Based on the results of bone mass and collagen/apatite orientation, combination treatment is an effective strategy. This is the first report to demonstrate the efficacy of IBN, ELD, and combination treatment with IBN and ELD relative to the bone micro-architectural anisotropy characterized by collagen/apatite orientation.

Bone fragility via degradation of bone quality featured by collagen/apatite micro-arrangement in human rheumatic arthritis.

Although increased bone fragility is a well-recognized consequence in patients with rheumatoid arthritis (RA), the essential cause of degenerate bone strength remains unknown. This study aimed to determine factors contributing to bone dysfunction in RA by focusing on the bone matrix micro-arrangement, based on the preferential orientation of collagen and the related apatite c-axis as a bone quality index. The classical understanding of RA is limited to its severe pathological conditions associated with inflammation-induced bone loss. This study examined periarticular proximal tibiae from RA patients as compared with osteoarthritis (OA) patients as controls. Bone tissue material strength was disrupted in the RA group compared with the control. Collagen/apatite micro-arrangement and vBMD were significantly lower in the RA group, and the rate of decrease in apatite c-axis orientation (-45%) was larger than that in vBMD (-22%). Multiple regression analysis showed that the degree of apatite c-axis orientation (ß = 0.52, p = 1.9 × 10-2) significantly contributed to RA-induced bone material impairment as well as vBMD (ß = 0.46, p = 3.8 × 10-2). To the best of our knowledge, this is the first report to demonstrate that RA reduces bone material strength by deteriorating the micro-arrangement of collagen/apatite bone matrix, leading to decreased fracture resistance. Our findings represent the significance of bone quality-based analysis for precise evaluation and subsequent therapy of the integrity and soundness of the bone in patients with RA.

Control of osteoblast arrangement by osteocyte mechanoresponse through prostaglandin E2 signaling under oscillatory fluid flow stimuli.

Anisotropic collagen/apatite microstructure is a prominent determinant of bone tissue functionalization; in particular, bone matrix modulates its anisotropic microstructure depending on the surrounding mechanical condition. Although mechanotransduction in bones is governed by osteocyte function, the precise mechanisms linking mechanical stimuli and anisotropic formation of collagen/apatite microstructure are poorly understood. Here we developed a novel anisotropic mechano-coculture system which enables the understanding of the biological mechanisms regulating the oriented bone matrix formation, which is constructed by aligned osteoblasts. The developed model provides bone-mimetic coculture platform that enables simultaneous control of mechanical condition and osteoblast-osteocyte communication with an anisotropic culture scaffold. The engineered coculture device helps in understanding the relationship between osteocyte mechanoresponses and osteoblast arrangement, which is a significant contributor to anisotropic organization of bone tissue. Our study showed that osteocyte responses to oscillatory flow stimuli regulated osteoblast arrangement through soluble molecular interactions. Importantly, we found that prostaglandin E2 is a novel determinant for oriented collagen/apatite organization of bone matrix, through controlling osteoblast arrangement.

Superior Alignment of Human iPSC-Osteoblasts Associated with Focal Adhesion Formation Stimulated by Oriented Collagen Scaffold.

Human-induced pluripotent stem cells (hiPSCs) can be applied in patient-specific cell therapy to regenerate lost tissue or organ function. Anisotropic control of the structural organization in the newly generated bone matrix is pivotal for functional reconstruction during bone tissue regeneration. Recently, we revealed that hiPSC-derived osteoblasts (hiPSC-Obs) exhibit preferential alignment and organize in highly ordered bone matrices along a bone-mimetic collagen scaffold, indicating their critical role in regulating the unidirectional cellular arrangement, as well as the structural organization of regenerated bone tissue. However, it remains unclear how hiPSCs exhibit the cell properties required for oriented tissue construction. The present study aimed to characterize the properties of hiPSCs-Obs and those of their focal adhesions (FAs), which mediate the structural relationship between cells and the matrix. Our in vitro anisotropic cell culture system revealed the superior adhesion behavior of hiPSC-Obs, which exhibited accelerated cell proliferation and better cell alignment along the collagen axis compared to normal human osteoblasts. Notably, the oriented collagen scaffold stimulated FA formation along the scaffold collagen orientation. This is the first report of the superior cell adhesion behavior of hiPSC-Obs associated with the promotion of FA assembly along an anisotropic scaffold. These findings suggest a promising role for hiPSCs in enabling anisotropic bone microstructural regeneration.

Quantitative Evaluation of Osteocyte Morphology and Bone Anisotropic Extracellular Matrix in Rat Femur.

Osteocytes are believed to play a crucial role in mechanosensation and mechanotransduction which are important for maintenance of mechanical integrity of bone. Recent investigations have revealed that the preferential orientation of bone extracellular matrix (ECM) mainly composed of collagen fibers and apatite crystallites is one of the important determinants of bone mechanical integrity. However, the relationship between osteocytes and ECM orientation remains unclear. In this study, the association between ECM orientation and anisotropy in the osteocyte lacuno-canalicular system, which is thought to be optimized along with the mechanical stimuli, was investigated using male rat femur. The degree of ECM orientation along the femur longitudinal axis was significantly and positively correlated with the anisotropic features of the osteocyte lacunae and canaliculi. At the femur middiaphysis, there are the osteocytes with lacunae that highly aligned along the bone long axis (principal stress direction) and canaliculi that preferentially extended perpendicular to the bone long axis, and the highest degree of apatite c-axis orientation along the bone long axis was shown. Based on these data, we propose a model in which osteocytes can change their lacuno-canalicular architecture depending on the mechanical environment so that they can become more susceptible to mechanical stimuli via fluid flow in the canalicular channel.

Impaired Alignment of Bone Matrix Microstructure Associated with Disorganized Osteoblast Arrangement in Malignant Melanoma Metastasis.

Malignant melanoma favors spreading to bone, resulting in a weakened bone with a high fracture risk. Here, we revealed the disorganized alignment of apatite crystals in the bone matrix associated with the homing of cancer cells by developing an artificially controlled ex vivo melanoma bone metastasis model. The ex vivo metastasis model reflects the progressive melanoma cell activation in vivo, resulting in decreased bone mineral density and expression of MMP1-positive cells. Moreover, less organized intercellular connections were observed in the neighboring osteoblasts in metastasized bone, indicating the abnormal and randomized organization of bone matrix secreted by disconnected osteoblasts. Our study revealed that the deteriorated microstructure associated with disorganized osteoblast arrangement was a determinant of malignant melanoma-related bone dysfunction.

3D Printing of Anisotropic Bone-Mimetic Structure with Controlled Fluid Flow Stimuli for Osteocytes: Flow Orientation Determines the Elongation of Dendrites.

Although three-dimensional (3D) bioprinting techniques enable the construction of various living tissues and organs, the generation of bone-like oriented microstructures with anisotropic texture remains a challenge. Inside the mineralized bone matrix, osteocytes play mechanosensing roles in an ordered manner with a well-developed lacunar-canaliculi system. Therefore, control of cellular arrangement and dendritic processes is indispensable for construction of artificially controlled 3D bone-mimetic architecture. Herein, we propose an innovative methodology to induce controlled arrangement of osteocyte dendritic processes using the laminated layer method of oriented collagen sheets, combined with a custom-made fluid flow stimuli system. Osteocyte dendritic processes showed elongation depending on the competitive directional relationship between flow and substrate. To the best of our knowledge, this study is the first to report the successful construction of the anisotropic bone-mimetic microstructure and further demonstrate that the dendritic process formation in osteocytes can be controlled with selective fluid flow stimuli, specifically by regulating focal adhesion. Our results demonstrate how osteocytes adapt to mechanical stimuli by optimizing the anisotropic maturation of dendritic cell processes.

A Novel Role of Interleukin-6 as a Regulatory Factor of Inflammation-Associated Deterioration in Osteoblast Arrangement.

Inflammatory disorders are associated with bone destruction; that is, deterioration in bone cell activities are under the control of the innate immune system. Macrophages play a central role in innate immunity by switching their polarized phenotype. A disturbed immune system causes aberrance in the ordered bone matrix microarrangement, which is a dominant determinant of bone tissue functionalization. However, the precise relationship between the immune system and bone tissue organization is unknown. In this study, the controlled in vitro co-culture assay results showed that M1-polarized macrophages disrupted the osteoblast alignment, which directly modulate the oriented bone matrix organization, by secreting pro-inflammatory cytokines. Notably, interleukin-6 was found to be a key regulator of unidirectional osteoblast alignment. Our results demonstrated that inflammatory diseases triggered bone dysfunction by regulating the molecular interaction between the immune system and bone tissue organization. These findings may contribute to the development of therapeutic targets for inflammatory disorders, including rheumatoid arthritis.

Selective patterning of netrin-1 as a novel guiding cue for anisotropic dendrogenesis in osteocytes.

Although protein patterning approaches have found widespread applications in tuning surface characteristics of biomaterials, selective control of growth in cell body and dendrites utilizing such platforms remains difficult. The functional roles assumed by cell body and dendrites in a physiological milieu have extremely high specificity. In particular, osteocytes embedded inside the mineralized bone matrix are interconnected via dendritic cell processes characterized by an anisotropic arrangement of the lacunar-canalicular system, where the fluid-flow inside the canaliculi system regulates the mechanoresponsive functionalization of bone. Control of cellular networks connected by dendritic cell processes is, therefore, imperative for constructing artificially controlled bone-mimetic structures and as an extension, for gaining insights into the molecular mechanisms underlying dendrogenesis inside the mineralized bone matrix. Here, we report an innovative strategy to induce controlled elongation of cell body or dendritic process structures in selective directions by using the inkjet printing technique. Artificial runways employing netrin-1, inspired by neural architecture, were utilized to trigger controlled elongation in the osteocyte dendritic processes in desired directions. This is the first report, to the best of our knowledge, demonstrating that anisotropic dendrogenesis of osteocytes can be controlled with selective patterning of extracellular proteins, specifically via the axon guidance ligand netrin-1.

Design and fabrication of Ti-Zr-Hf-Cr-Mo and Ti-Zr-Hf-Co-Cr-Mo high-entropy alloys as metallic biomaterials.

Novel TiZrHfCr0.2Mo and TiZrHfCo0.07Cr0.07Mo high-entropy alloys for metallic biomaterials (bio-HEAs) were developed based on the combination of Ti-Nb-Ta-Zr-Mo alloy system and Co-Cr-Mo alloy system as commercially-used metallic biomaterials. Ti-Zr-Hf-Cr-Mo and Ti-Zr-Hf-Co-Cr-Mo bio-HEAs were designed using (a) a tree-like diagram for alloy development, (b) empirical alloy parameters for solid-solution-phase formation, and (c) thermodynamic calculations focused on solidification. The newly-developed bio-HEAs overcomes the limitation of classical metallic biomaterials by the improvement of (i) mechanical hardness and (ii) biocompatibility all together. The TiZrHfCr0.2Mo and TiZrHfCo0.07Cr0.07Mo bio-HEAs showed superior biocompatibility comparable to that of commercial-purity Ti. The superior biocompatibility, high mechanical hardness and low liquidus temperature for the material processing in TiZrHfCr0.2Mo and TiZrHfCo0.07Cr0.07Mo bio-HEAs compared with the Ti-Nb-Ta-Zr-Mo bio-HEAs gave the authenticity of the application of bio-HEAs for orthopedic implants with multiple functions.

Unique arrangement of bone matrix orthogonal to osteoblast alignment controlled by Tspan11-mediated focal adhesion assembly.

During tissue construction, cells coordinate extracellular matrix (ECM) assembly depending on the cellular arrangement. The traditional understanding of the relationship between the ECM and cells is limited to the orientation-matched interaction between them. Indeed, it is commonly accepted that the bone matrix (collagen/apatite) is formed along osteoblast orientation. Nonetheless, our recent findings are contrary to the above theory; osteoblasts on nanogrooves organize formation of the bone matrix perpendicular to cell orientation. However, the precise molecular mechanisms underlying the orthogonal organization of bone matrix are still unknown. Here, we show that mature fibrillar focal adhesions (FAs) facilitate the perpendicular arrangement between cells and bone matrix. The osteoblasts aligned along nanogrooves expressed highly mature fibrillar FAs mediated by integrin clustering. Microarray analysis revealed that Tspan11, a member of the transmembrane tetraspanin protein family, was upregulated in cells on the nanogrooved surface compared with that in cells on isotropic, flat, or rough surfaces. Tspan11 silencing significantly disrupted osteoblast alignment and further construction of aligned bone matrix orthogonal to cell orientation. Our results demonstrate that the unique bone matrix formation orthogonal to cell alignment is facilitated by FA maturation. To the best of our knowledge, this report is the first to show that FA assembly mediated by Tspan11 determines the direction of bone matrix organization.

Development of bifunctional oriented bioactive glass/poly(lactic acid) composite scaffolds to control osteoblast alignment and proliferation.

During the bone regeneration process, the anisotropic microstructure of bone tissue (bone quality) recovers much later than bone mass (bone quantity), resulting in severe mechanical dysfunction in the bone. Hence, restoration of bone microstructure in parallel with bone mass is necessary for ideal bone tissue regeneration; for this, development of advanced bifunctional biomaterials, which control both the quality and quantity in regenerated bone, is required. We developed novel oriented bioactive glass/poly(lactic acid) composite scaffolds by introducing an effective methodology for controlling cell alignment and proliferation, which play important roles for achieving bone anisotropy and bone mass, respectively. Our strategy is to manipulate the cell alignment and proliferation by the morphological control of the scaffolds in combination with controlled ion release from bioactive glasses. We quantitatively controlled the morphology of fibermats containing bioactive glasses by electrospinning, which successfully induced cell alignment along the fibermats. Also, the substitution of CaO in Bioglass®(45S5) with MgO and SrO improved osteoblast proliferation, indicating that dissolved Mg2+ and Sr2+ ions promoted cell adhesion and proliferation. Our results indicate that the fibermats developed in this work are candidates for the scaffolds to bone tissue regeneration that enable recovery of both bone quality and bone quantity. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1031-1041, 2019.