Decoding bone-inspired and cell-instructive cues of scaffolds for bone tissue engineering

Currently available bone grafts present certain limitations such as donor-site morbidity for autografts and risk of disease transmission for allografts. These limitations suggest a need for alternative strategies. The use of polymer/ceramic composites as scaffolds for trabecular bone tissue engineering capitalizes on the benefits of both materials. Polymers are easily formed and shaped and add structural rigidity while calcium phosphates impart osteoconductivity and osteointegration. We have developed a biodegradable, microsphere-based scaffold for bone tissue engineering based on poly(lactide-co-glycolide)/calcium phosphate composite microspheres in which a nanocrystalline hydroxyapatite is synthesized within the forming microspheres.

Electrospinning is a promising and versatile technique that is used to fabricate polymeric nanofibrous scaffolds for bone tissue engineering. Ideal scaffolds should be biocompatible and bioactive with appropriate surface chemistry, good mechanical properties and should mimic the natural extracellular matrix (ECM) of bone. Selection of the most appropriate material to produce a scaffold is an important step towards the construction of a tissue engineered product. Bone tissue engineering is an interdisciplinary field, where the principles of engineering are applied on bone-related biochemical reactions. Scaffolds, cells, growth factors, and their interrelation in microenvironment are the major concerns in bone tissue engineering. This review covers the latest development of biomimetic electrospun polymeric biomaterials for bone tissue engineering. It includes the brief details to bone tissue engineering along with bone structure and ideal bone scaffolds requirements. Details about various engineered materials and methodologies used for bone scaffolds development were discussed. Description of electrospinning technique and its parameters relating their fabrication, advantages, and applications in bone tissue engineering were also presented. The use of synthetic and natural polymers based electrospun nanofibrous scaffolds for bone tissue engineering and their biomineralization processes were discussed and reviewed comprehensively. Finally, we give conclusion along with perspectives and challenges of biomimetic scaffolds for bone tissue engineering based on electrospun nanofibers.

Decellularized periosteum as a potential biologic scaffold for bone tissue engineering

Development of a demineralized and decellularized human epiphyseal bone scaffold for tissue engineering: A histological study.

Event Abstract Back to Event Bio-functionalization of nHA/PLGA hybrid nanofiber scaffolds for bone tissue engineering Adnan Haider1 and Inn-Kyu Kang1 1 Kyungpook National University, Department of Polymer Science and Engineering, Korea Introduction: Developing a scaffold for tissue engineering requires special properties such as the scaffolds should mimic the ECM matrix and provided native environment to the cultured cells. Among the various techniques used for the fabrication of such scaffolds electrospinning has been considered vitally important. Electrospinning technique enabled the researchers to fabricate wide range of scaffolds from variety of polymer both of natural and synthetic origin. In order to mimic the ECM the polymeric scaffolds should have biocompatibility and biodegradability. Among the tested polymers, PLGA has attracted the scientific community towards its use in the fabrication of scaffolds for biomedical application. Moreover it has also been approved by the FDA due to its biocompatible and biodegradable nature. PLGA is a copolymer made up of different ratio of lactide and glycolide. The versatility, degradation time and usage of PLGA arise from the monomers ratio. PLGA having 15% of lactide is specially chosen when long degradation time is required. Materials and Method: Bone morphogenetic protein was purchased from Korea bone bank, Poly (lactide-co-glycolide) (PLGA, 85:15) and insulin from human pancreas were obtained from Sigma Aldrich. Pamidronic acid was purchased from Santa cruz Biotechnology. Nanorod shaped hydroxyapatite(nHA) was synthesized in the laboratory. MEM alpha, osteoblasts and macrophages(RAW 264.7) which were differentiated into osteoclast by using MCSF and RANKL were purchased from Korea cell bank. 5-Bromo-2-deoxyuridine (BrdU) and alizarin red staining kit were purchased from Roche Molecular Biochemicals and Millipore, (USA), respectively. Whereas fetal bovine serum (FBS) and penicillin G-streptomycin were purchased from Gibco, Japan. All the reagents and chemicals in this study were used without any further purification. Results and Discussion: Insulin (I), bone morphogenetic protein (BMP-2) and pamidronic acid (PDA) were successfully grafted on the surface of hydroxyapatite nanorods (nHA). The insulin, BMP-2 and PDA grafted nHA (I-g-nHA, BMP-2-g-nHA, and PDA-g-nHA) were individually mixed with PLGA polymeric solution and subjected to electrospining for the generation of smooth and uniform hybrid nanofiber scaffolds. After the confirmational characterization, the hybrid nanofiber scaffolds were subjected to in vitro cell study in order to assess their cyto-compatibilty. The pristine PLGA and nHA/PLGA nanofiber scaffolds were used as control in all the experiments. The results obtained from the in vtro experiments suggested that the I-g-nHA/PLGA and BMP-2-g- nHA/PLGA hybrid nanofiber scaffolds enhanced osteoblastic cells growth as compared to the nHA/PLGA and pristine PLGA nanofiber scaffolds. On the other hand, PDA-g-nHA/PLGA hybrid nanofiber scaffolds suppressed osteoclastic cells activity and enhanced osteoblastic cells activity due to the presence of pamidronic acid and nHA, respectively. Conclusion: We fabricated various kind of hybrid nanofiber scaffolds loaded with proteins and drug such as insulin, bone morphogenetic protein and pamidronic acid for enhancing bone tissue regeneration and suppressing bone resorption. After the characterization the scaffolds were subjected to in vitro testing for assessing osteoblastic cells response towards these hybrid nanofiber scaffolds. From the data obtained it was concluded that proteins and drug loaded hybrid nanofiber scaffolds has the potential to increase osteogenesis, These scaffolds can be regarded as a step forward in the study of bone tissue regeneration and cure of bone related diseases. "This work was supported by the general research program (2013 RIAIA 2005148) from the Ministry of Education, Science and Technology of South Korea, and the Basic Research Laboratory program (No 2011-0020264)." Keywords: Scaffold, Biocompatibility, Tissue Regeneration, Biodegradable material Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Biomimetic materials Citation: Haider A and Kang I (2016). Bio-functionalization of nHA/PLGA hybrid nanofiber scaffolds for bone tissue engineering. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01407 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Adnan Haider Inn-Kyu Kang Google Adnan Haider Inn-Kyu Kang Google Scholar Adnan Haider Inn-Kyu Kang PubMed Adnan Haider Inn-Kyu Kang Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The optimization of enzyme-mediated polymerization of pentadecalactone (PDL) was performed to obtain macromolecular products suitable for generation of 3D cell supports (scaffolds) for bone tissue engineering. Such parameters as temperature, monomer/enzyme ratio, and monomer concentration were studied. The maximum molecular weight of synthesized polymers was about 90,000. Methods allowing the introduction of reactive double bonds into polypentadecalactone (polyPDL) structure were developed. The macroporous matrices were obtained by modification of thermoinduced phase separation method.

In the past 20 years, mesoporous materials have been attracted great attention due to their significant feature of large surface area, ordered mesoporous structure, tunable pore size and volume, and well-defined surface property. They have many potential applications, such as catalysis, adsorption/separation, biomedicine, etc. [1]. Recently, the studies of the applications of mesoporous materials have been expanded into the field of biomaterials science. A new class of bioactive glass, referred to as mesoporous bioactive glass (MBG), was first developed in 2004. This material has a highly ordered mesopore channel structure with a pore size ranging from 5–20 nm [1]. Compared to non-mesopore bioactive glass (BG), MBG possesses a more optimal surface area, pore volume and improved in vitro apatite mineralization in simulated body fluids [1,2]. Vallet-Regi et al. has systematically investigated the in vitro apatite formation of different types of mesoporous materials, and they demonstrated that an apatite-like layer can be formed on the surfaces of Mobil Composition of Matters (MCM)-48, hexagonal mesoporous silica (SBA-15), phosphorous-doped MCM-41, bioglass-containing MCM-41 and ordered mesoporous MBG, allowing their use in biomedical engineering for tissue regeneration [2-4]. Chang et al. has found that MBG particles can be used for a bioactive drug-delivery system [5,6]. Our study has shown that MBG powders, when incorporated into a poly (lactide-co-glycolide) (PLGA) film, significantly enhance the apatite-mineralization ability and cell response of PLGA films. compared to BG [7]. These studies suggest that MBG is a very promising bioactive material with respect to bone regeneration. It is known that for bone defect repair, tissue engineering represents an optional method by creating three-dimensional (3D) porous scaffolds which will have more advantages than powders or granules as 3D scaffolds will provide an interconnected macroporous network to allow cell migration, nutrient delivery, bone ingrowth, and eventually vascularization [8]. For this reason, we try to apply MBG for bone tissue engineering by developing MBG scaffolds. However, one of the main disadvantages of MBG scaffolds is their low mechanical strength and high brittleness; the other issue is that they have very quick degradation, which leads to an unstable surface for bone cell growth limiting their applications. Silk fibroin, as a new family of native biomaterials, has been widely studied for bone and cartilage repair applications in the form of pure silk or its composite scaffolds [9-14]. Compared to traditional synthetic polymer materials, such as PLGA and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), the chief advantage of silk fibroin is its water-soluble nature, which eliminates the need for organic solvents, that tend to be highly cytotoxic in the process of scaffold preparation [15]. Other advantages of silk scaffolds are their excellent mechanical properties, controllable biodegradability and cytocompatibility [15-17]. However, for the purposes of bone tissue engineering, the osteoconductivity of pure silk scaffolds is suboptimal. It is expected that combining MBG with silk to produce MBG/silk composite scaffolds would greatly improve their physiochemical and osteogenic properties for bone tissue engineering application. Therefore, in this chapter, we will introduce the research development of MBG/silk scaffolds for bone tissue engineering.

Calcium phosphate ceramics have been widely considered as scaffolds for bone tissue engineering. Selection of the best support for cultured cells, crucial for tissue engineered systems, is still required. We examined three types of calcium phosphate compounds: α-tricalcium phosphate - the most soluble one, carbonate hydroxyapatite - chemically the most similar to the bone mineral and biphasic calcium phosphate - with the best in vivo biocompatibility in order to select the best support for osteoblastic cells for tissue engineered systems. Human osteoblasts were tested in direct contact with both dense samples and 3D scaffolds in either static or dynamic culture. Cell viability, cell spreading, osteogenic cell capacity, and extracellular matrix production were examined. The obtained data indicate that biphasic calcium phosphate is the optimal cell-supporting material. In addition, dynamic culture improved cell distribution in the scaffolds, enhanced production of the extracellular matrix and promoted cells osteogenic capacity. Biphasic calcium phosphate should be recommended as the most suitable matrix for osteogenic cells expansion and differentiation in tissue engineered systems.

Tissue grafting is mostly used for repair and replacement of severely damaged tissues, the key challenges are compatibility, availability of the grafts, complex surgical process and post-operative complications. Hence, additive technologies such as three-dimensional (3D) bioprinting have emerged as promising alternative for tissue engineering in order to ensure safety, compatibility, and rapid healing. The aim of this chapter is to give an elaborate account of 3D printed scaffolds for bone, cartilage, cardio-vascular and nerve tissue engineering. Various components such as polycaprolactone, poly (lactic-co-glycolic acid), and β-tricalcium phosphate, bioglass 45S5, and nano-hydroxyapatite are combined with collagen and its derivatives to achieve specific pore size in the scaffolds for effective restoration of the defects of soft or hard tissues. Likewise, proanthocyanidin, oxidized hyaluronic acid, methacrylated gelatin, are used in collagen based 3D printed scaffolds for cartilage tissue engineering. Bioink with collagen as active component is also used for developing cardio-vascular implants with recellularizing properties. Collagen in combination with silk fibroin, chitosan, heparin sulphate and others are ideal for fabrication of elastic nerve guidance conduits. In view of the background, collagen-supplemented hydrogels can revolutionize future biomedical approaches for the development of complex scaffolds for tissue engineering.

To enhance the understanding and usefulness of decellularised plant tissues as scaffolds for bone tissue engineering, and to review the recent advances in plant-based scaffolds for bone regeneration. The systematic review was conducted from February to June 2022, and comprised literature search on PubMed and Science Direct databases for articles published in the English language between 2013 and June, 2022. The search was conducted using key words 'plant-based scaffolds and osteogenesis' and 'decellularised plant and scaffolds and bone tissue engineering' and 'plant root-based scaffold and bone formation'. Full-text articles and short communication covering both in vitro and in vivo studies focussing on plant-based scaffolds for osteogenesis were included. Additional references that satisfied the inclusion criteria were found on Google Scholar and included in the review. Quality evaluation of the studies included was done independently by two researchers, and the risk of bias was calculated and categorised as low, medium and high risk. Of the 564 articles, 10(1.77 %) were included; 6(60%) purely in vitro studies, and 4(40%) studies having both in vitro and in vivo components. Decellularized plant tissue alone was used as three-dimensional scaffold materials in 5(50%) studies, but in 4(40%) studies, plant-based composite scaffolds were used. The risk of bias was medium in 7(70%) studies. Plant-based scaffolds promote osteogenesis, but more in vivo research on plant-based studies is needed to label it as suitable scaffolds for bone tissue engineering.

The potential of melt-electrowriting (MEW) to fabricate highly porous 3D composite scaffolds for bone tissue engineering (BTE) with antibacterial properties was explored. Zinc oxide (ZnO) nanoparticles (NPs) were loaded into biodegradable medical grade Polycaprolactone (PCL) loaded with 10 wt% hydroxyapatite (HA) NPs to create antibacterial constructs by the MEW technique. The constructs’ morphology, chemical, thermal and mechanical properties, osteoblasts cell viability and bacterial attachment were investigated. Our results demonstrate a unique homogeneous dispersion of ZnO-HA NPs in the outer shell of the fabricated composite fibres by MEW, leading to significant inhibition of bacterial attachment against microorganisms while retaining osteoiblast viability. This novel composite MEW 3D scaffolds yielded promising multifunctional constructs with high potential in BTE.

In this work, the fabrication and in vitro degradation of porous fumarate-based/alumoxane nanocomposites were evaluated for their potential as bone tissue engineering scaffolds. The biodegradable polymer poly (propylene fumarate)/propylene fumarate-diacrylate (PPF/PF-DA), a macrocomposite composed of PPF/PF-DA and boehmite microparticles, and a nanocomposite composed of PPF/PF-DA and surface-modified alumoxane nanoparticles were used to fabricate porous scaffolds by photo-crosslinking and salt-leaching. Scaffolds then underwent 12 weeks of in vitro degradation in phosphate buffered saline at 37 degrees C. The presence of boehmite microparticles and alumoxane nanoparticles in the polymer inhibited scaffold shrinkage during crosslinking. Furthermore, the incorporation of alumoxane nanoparticles into the polymer limited salt-leaching, perhaps due to tighter crosslinking within the nanocomposite. Analysis of crosslinking revealed that the acrylate and overall double bond conversions in the nanocomposite were higher than in the PPF/PF-DA polymer alone, though these differences were not significant. During 12 weeks of in vitro degradation, the nanocomposite lost 5.3% +/- 2.4% of its mass but maintained its compressive mechanical properties and porous architecture. The addition of alumoxane nanoparticles into the fumarate-based polymer did not significantly affect the degradation of the nanocomposite compared with the other materials in terms of mass loss, compressive properties, and porous structure. These results demonstrate the feasibility of fabricating degradable nanocomposite scaffolds for bone tissue engineering by photo-crosslinking and salt-leaching mixtures of fumarate-based polymers, alumoxane nanoparticles, and salt microparticles.

The effects of collagen concentration and crosslink density on the biological, structural and mechanical properties of collagen-GAG scaffolds for bone tissue engineering

Development and assessment of modified-honeycomb-structure scaffold for bone tissue engineering

Coaxial electrospun aligned tussah silk fibroin nanostructured fiber scaffolds embedded with hydroxyapatite-tussah silk fibroin nanoparticles for bone tissue engineering.