Production of new 3D scaffolds for bone tissue regeneration by rapid prototyping

The incidence of bone disorders, whether due to trauma or pathology, has been trending upward with the aging of the worldwide population. The currently available treatments for bone injuries are rather limited, involving mainly bone grafts and implants. A particularly promising approach for bone regeneration uses rapid prototyping (RP) technologies to produce 3D scaffolds with highly controlled structure and orientation, based on computer-aided design models or medical data. Herein, tricalcium phosphate (TCP)/alginate scaffolds were produced using RP and subsequently their physicochemical, mechanical and biological properties were characterized. The results showed that 60/40 of TCP and alginate formulation was able to match the compression and present a similar Young modulus to that of trabecular bone while presenting an adequate biocompatibility. Moreover, the biomineralization ability, roughness and macro and microporosity of scaffolds allowed cell anchoring and proliferation at their surface, as well as cell migration to its interior, processes that are fundamental for osteointegration and bone regeneration.     

Porous ceramic bone scaffolds for vascularized bone tissue regeneration

Hydroxyapatite scaffolds with a multi modal porosity designed for use in tissue engineering of vascularized bone graft substitutes were prepared by three dimensional printing. Depending on the ratio of coarse (mean particle size 50 microm) to fine powder (mean particle size 4 microm) in the powder granulate and the sintering temperature total porosity was varied from 30% to 64%. While macroscopic pore channels with a diameter of 1 mm were created by CAD design, porosity structure in the sintered solid phase was governed by the granulate structure of the printing powder. Scaffolds sintered at 1,250 degrees C were characterized by a bimodal pore structure with intragranular pores of 0.3-0.4 microm and intergranular pores of 20 microm whereas scaffolds sintered at 1,400 degrees C exhibit a monomodal porosity with a maximum of pore size distribution at 10-20 microm. For in-vivo testing, matrices were implanted subcutaneously in four male Lewis rats. Scaffolds with 50% porosity and an average pore size of approximately 18 microm were successfully transferred to rats and vascularized within 4 weeks.     

A conceptually new type of bio-hybrid scaffold for bone regeneration

Magnetic bio-hybrid porous scaffolds have been synthesized, nucleating nano-apatite in situ on self-assembling collagen, in the presence of magnetite nano-particles. The magnetic phase acted as a sort of cross-linking agent for the collagen, inducing a chemico-physical-mechanical stabilization of the material and allowing us to control the porosity network of the scaffold. Gradients of bio-mineralization and magnetization were also developed for osteochondral application. The good potentiality of the material as a biomedical device, able to offer assistance to bone regeneration through scaffold reloading with specific factors guided by an external magnetic field, has been preliminarily investigated. Up to now the proof of this concept has been realized through in vitro assessments.     

A novel sheep vertebral bone defect model for injectable bioactive vertebral augmentation materials

New injectable bone substitutes have been developed that are, unlike polymethylmethacrylate, biologically active and have an osteogenic effect leading to osteogenesis and bone remodeling for vertebroplasty or kyphoplasty. In this study, we developed a sheep vertebral bone defect model to evaluate the new bioactive materials and assessed the feasibility of the model in vivo. Bone voids were experimentally created on lumbar vertebrae L2–L5 with L1 and L6 left intact as a normal control in mature sheep. The defect vertebrae L2–L5 in each sheep were randomized to receive augmentation with calcium phosphate cement (CPC) or sham. Vertebrae (L1–L6) were collected after 2 and 24 weeks of the cement augmentation and their strength and stiffness, as well as osseointegration activity and biodegradability, were evaluated. Finally, CPC significantly improved the strength and stiffness of vertebrae but did not yet restore it to the normal level at 24 weeks. Osteogenesis occurred at a substantially high level after 24 weeks of CPC augmentation or sham. Therefore, the sheep vertebral model with one void, 6.0 mm in diameter and 15.0 mm in depth, is replicable and can be used for evaluating the new injectable bioactive materials in vertebral augmentation or reconstruction.     

Engineering vascularized and innervated bone biomaterials for improved skeletal tissue regeneration

Blood vessels and nerve fibers are distributed throughout the entirety of skeletal tissue, and play important roles during bone development and fracture healing by supplying oxygen, nutrients, and cells. However, despite the successful development of bone mimetic materials that can replace damaged bone from a structural point of view, most of the available bone biomaterials often do not induce sufficient formation of blood vessels and nerves. In part, this is due to the difficulty of integrating and regulating multiple tissue types within artificial materials, which causes a gap between native skeletal tissues. Therefore, understanding the anatomy and underlying interaction mechanisms of blood vessels and nerve fibers in skeletal tissue is important to develop biomaterials that can recapitulate its complex microenvironment. In this perspective, we highlight the structure and osteogenic functions of the vascular and nervous systems in bone, in a coupled manner. In addition, we discuss important design criteria for engineering vascularized, innervated, and neurovascularized bone implant materials, as well as recent advances in the development of such biomaterials. We expect that bone implant materials with neurovascularized networks can more accurately mimic native skeletal tissue and improve the regeneration of bone tissue.     

In vitro evaluation of bioactive strontium-based ceramic with rabbit adipose-derived stem cells for bone tissue regeneration

The development of bone replacement materials is an important objective in the field of orthopaedic surgery. Due to the drawbacks of treating bone defects with autografts, synthetic bone graft materials have become optional. So in this work, a bone tissue engineering approach with radiopaque bioactive strontium incorporated calcium phosphate was proposed for the preliminary cytocompatibility studies for bone substitutes. Accumulating evidence indicates that strontium containing biomaterials promote enhanced bone repair and radiopacity for easy imaging. Hence, strontium calcium phosphate (SrCaPO₄) and hydroxyapatite scaffolds have been investigated for its ability to support and sustain the growth of rabbit adipose-derived mesenchymal stem cells (RADMSCs) in vitro. They were characterized via Micro-CT for pore size distribution. Cells used were isolated from New Zealand White rabbit adipose tissue, characterized by FACS and via differentiation into the osteogenic lineage by alkaline phosphatase, Masson’s trichome, Alizarin Red and von Kossa staining on day 28. Material-cell interaction was observed by SEM imaging of cell morphology on contact with material. Live–Dead analysis was done by confocal laser scanning microscopy and cell cluster analysis via μCT. The in vitro biodegradation, elution and nucleation of apatite formation of the material was evaluated using simulated body fluid and phosphate buffered saline in static regime up to 28 days at 37 °C. These results demonstrated that SrCaPO₄ is a good candidate for bone tissue engineering applications and with osteogenically-induced RADMSCs, they may serve as potential implants for the repair of critical-sized bone defects.     

Shell Scaffolds: A new approach towards high strength bioceramic scaffolds for bone regeneration

A key issue for bone tissue engineering is the design of bioceramic scaffolds combining high porosity with adequate mechanical properties. Furthermore, a resistant surface is required in order to have manageable samples for both in vivo and in vitro applications. Here a new protocol that aims at giving an appropriate response to these issues is developed. The realized shell scaffolds, obtained by combining a modified replication technique with the usual polymer burning-out method, look rather promising mainly thanks to their manageability, porosity and permeability. In this preliminary work the developed technique is discussed, together with an overview on the structure of the realized samples.     

一种新的潜在语义分析语言模型

提出了基于聚类的方法实现词的快速量化表示,并由此导出潜在语义分析语言模型预测置信度,同时运用新提出的几何加权静态插值方式同三元文法模型相结合,构建了一种新的潜在语义分析语言模型,并将其应用于汉语语音识别。实验表明其效率和性能均优于传统基于奇异值分解的潜在语义分析语言模型,相比于三元文法模型,识别错误率相对下降为3．6％～7．1％左右,并为有效量化表示词对进一步提高潜在语义分析语言模型性能提供了新的途径。     

Novel biomimetic hydroxyapatite/alginate nanocomposite fibrous scaffolds for bone tissue regeneration

Hydroxyapatite/alginate nanocomposite fibrous scaffolds were fabricated via electrospinning and a novel in situ synthesis of hydroxyapatite (HAp) that mimics mineralized collagen fibrils in bone tissue. Poorly crystalline HAp nanocrystals, as confirmed by X-ray diffractometer peak approximately at 2θ = 32° and Fourier transform infrared spectroscopy spectrum with double split bands of PO₄(v ₄) at 564 and 602 cm^?1, were induced to nucleate and grow at the [–COO^?]–Ca²⁺–[–COO^?] linkage sites on electrospun alginate nanofibers impregnated with PO₄ ^3? ions. This novel process resulted in a uniform deposition of HAp nanocrystals on the nanofibers, overcoming the severe agglomeration of HAp nanoparticles processed by the conventional mechanical blending/electrospinning method. Preliminary in vitro cell study showed that rat calvarial osteoblasts attached more stably on the surface of the HAp/alginate scaffolds than on the pure alginate scaffold. In general, the osteoblasts were stretched and elongated into a spindle-shape on the HAp/alginate scaffolds, whereas the cells had a round-shaped morphology on the alginate scaffold. The unique nanofibrous topography combined with the hybridization of HAp and alginate can be advantageous in bone tissue regenerative medicine applications.     

Approaches to the fabrication of calcium phosphate-based porous materials for bone tissue regeneration

This paper reviews advances in the fabrication of calcium phosphate materials for injured bone tissue regeneration. We examine the key features of rapid prototyping for the fabrication of porous ceramic scaffolds with tailored architectures, the technology of biopolymer-based composite materials reinforced with calcium phosphate particles, and the fabrication of porous scaffolds via cement route.     

Nano- and micro-fiber combined scaffolds: A new architecture for bone tissue engineering

One possible interesting way of designing a scaffold for bone tissue engineering is to base it on trying to mimic the biophysical structure of natural extracellular matrix (ECM). This work was developed in order to produce scaffolds for supporting bone cells. Nano and micro fiber combined scaffolds were originally produced from starch based biomaterials by means of a fiber bonding and a electrospinning, two step methodology. The cell culture studies with SaOs-2 human osteoblast-like cell line and rat bone marrow stromal cells demonstrated that presence of nanofibers influenced cell shape and cytoskeletal organization of the cells on the nano/micro combined scaffolds. Moreover, cell viability and Alkaline Phosphatase (ALP) activity for both cell types was found to be higher in nano/micro combined scaffolds than in control scaffolds based on fiber meshes without nanofibers. Consequently, the developed structures are believed have a great potential on the 3D organization and guidance of cells that is provided for engineering of 3-dimensional bone tissues.     

Structure and functionalization of mesoporous bioceramics for bone tissue regeneration and local drug delivery

This review article describes the importance of structure and functionalization in the performance of mesoporous silica bioceramics for bone tissue regeneration and local drug delivery purposes. Herein, we summarize the pivotal features of mesoporous bioactive glasses, also known as 'templated glasses' (TGs), which present chemical compositions similar to those of conventional bioactive sol-gel glasses and the added value of an ordered mesopore arrangement. An in-depth study concerning the possibility of tailoring the structural and textural characteristics of TGs at the nanometric scale and their influence on bioactive behaviour is discussed. The highly ordered mesoporous arrangement of cavities allows these materials to confine drugs to be subsequently released, acting as drug delivery devices. The functionalization of mesoporous silica walls has been revealed as the cornerstone in the performance of these materials as controlled release systems. The synergy between the improved bioactive behaviour and local sustained drug release capability of mesostructured materials makes them suitable to manufacture three-dimensional macroporous scaffolds for bone tissue engineering. Finally, this review tackles the possibility of covalently grafting different osteoinductive agents to the scaffold surface that act as attracting signals for bone cells to promote the bone regeneration process.     

Digital innovations-driven business model regeneration: A process model

The traditional ways of doing business have changed dramatically with the emergence of new digital technologies. Firms can stay competitive using the benefits of digital technologies, such as the Internet of Things, social computing, Cloud computing, cyber-physical systems, big data and analytics, wireless networks, artificial intelligence, robotics, simulation, etc. The spread of the coronavirus disease in 2019 (COVID-19) all over the world has created a better understanding of the importance of organizations’ ability to keep up with digital innovations. Therefore, the regeneration of business models is becoming an increasingly crucial factor for survival in the digital age. This study develops a process model for digital innovations-driven business model regeneration based on the design science research approach. For this purpose, the existing models and cases in the business model innovation (BMI) literature are examined and the empirical data are collected using semi-structured interviews to complement and validate this knowledge. The collected data are then analyzed and a digital innovations-driven business model regeneration method is developed. The proposed model is demonstrated with a real case. This study extends the BMI literature. The proposed process model can be used by strategic managers to analyze the impacts of potential digital innovations on their current business models and regenerate their business model. Therefore, it can help companies to be able to gain a competitive advantage over their competitors or sustain their business against technological developments.     

Hybrid bilayered chitosan-xanthan/PCL scaffolds as artificial periosteum substitutes for bone tissue regeneration

Journal of Materials Science - The periosteum, a bilayered membrane that covers bone surfaces, acts as a source of bone-forming cells and plays a pivotal role in bone homeostasis and defect...     

Polysaccharide nanofibrous scaffolds as a model for in vitro skin tissue regeneration

Tissue engineering and nanotechnology have advanced a general strategy combining the cellular elements of living tissue with sophisticated functional biocomposites to produce living structures of sufficient size and function at a low cost for clinical relevance. Xylan, a natural polysaccharide was electrospun along with polyvinyl alcohol (PVA) to produce Xylan/PVA nanofibers for skin tissue engineering. The Xylan/PVA glutaraldehyde (Glu) vapor cross-linked nanofibers were characterized by SEM, FT-IR, tensile testing and water contact angle measurements to analyze the morphology, functional groups, mechanical properties and wettability of the fibers for skin tissue regeneration. The cell-biomaterial interactions were studied by culturing human foreskin fibroblasts on Xylan/PVA Glu vapor cross-linked and Xylan/PVA/Glu blend nanofibrous scaffolds. The observed results showed that the mechanical properties (72 %) and fibroblast proliferation significantly increased up to 23 % (P < 0.05) in 48 h Glu vapor cross-linked nanofibers compared to 24 h Glu vapor cross-linked Xylan/PVA nanofibers. The present study may prove that the natural biodegradable Xylan/PVA nanofibrous scaffolds have good potential for fibroblast adhesion, proliferation and cell matrix interactions relevant for skin tissue regeneration.     

A simple method of cartilage regeneration using a new polymerizing system: ultrastructural characteristics of the repair tissue

The ultrastructural characteristics of the repair tissue in large articular cartilage defects, filled with a heterocyclic polymerizing system were studied using transmission electron microscopy (TEM) and energy dispersive micro-analysis (EDMA). By six weeks post-implantation, the defects were resurfaced with predominantly hyaline-like articular cartilage. Chondrocytes in both the superficial and deep zones of the repair tissue were highly productive, secreting large amounts of proteoglycans, into a well-organized, rich in collagen fibrils, extracellular matrix. By contrast, in the repair tissue of the defects treated without the biomaterial, proteoglycan synthesis was less and the structure of the matrix was inferior. We conclude that the polymer enhances both chondrocyte metabolism and matrix organization, thus improving the quality of the repair tissue in articular cartilage defects.     

A new combinatorial model for deterministic competing failure analysis

Components in many engineering and industrial systems can experience propagated failures, which not only cause the failure of the component itself but also affect other components, causing extensive damage to the entire system. However, in systems with functional dependence behavior where failure of a trigger component may cause other components (referred to as dependent components) to become unusable or inaccessible, failure propagation originating from a dependent component could be isolated if the corresponding trigger component fails first. Thus, a time-domain competition exists between the failure propagation effect and the failure isolation effect, which poses a great challenge to the system reliability modeling and analysis. In this work, a new combinatorial model called competing binary decision diagram (CBDD) is proposed for the reliability analysis of systems subject to the competing failure behavior. In particular, special Boolean algebra rules and logic manipulation rules are developed for system CBDD model generation. The corresponding evaluation algorithm for the constructed CBDD model is also proposed. The proposed CBDD modeling method has no limitation on the type of component time-to-failure distributions. A memory system example and a network example are provided to demonstrate the application of the proposed model and algorithms. Correctness of the proposed method is verified using the Markov method.     

Preparation and characterization of polycaprolactone/forsterite nanocomposite porous scaffolds designed for bone tissue regeneration

Biocomposite scaffolds made from polymers and bioceramics can provide the mechanical structure necessary for osteoinductivity in the growth of new bone. The aim of this research was to investigate the properties of a novel nanocomposite scaffold made from a combination of polycaprolactone (PCL) and forsterite nanopowder which could find use in bone tissue engineering applications. The scaffold itself was fabricated by a method of solvent casting and particle leaching. The effect of forsterite content on the mechanical properties, bioactivity, biodegradability, and cytotoxicity of the scaffolds was investigated. Significant improvement in the mechanical properties was observed in the nanocomposite scaffolds as compared to that seen in the pure PCL scaffolds. Bioactivity was also observed in the nanocomposite scaffolds, a trait which was not present in the pure PCL scaffolds. Biodegradation assay indicated that the addition of forsterite nanopowder could modulate the degradation rate of PCL. In vitro tests of cytotoxicity and osteoblast proliferation showed that the nanocomposite scaffolds were non-cytotoxic, thereby allowing cells to adhere, grow, and proliferate on the surface of these scaffolds. The results obtained in this experiment suggest that the combination of PCL with forsterite nanopowder can be used to form scaffolds suitable for use in bone tissue engineering. The exact material behavior required can be adjusted through variation of the ratio between PCL and forsterite nanopowder used to form the scaffold.