Micro‐Nanostructures of Cellulose‐Collagen for Critical Sized Bone Defect Healing

Bone tissue engineering strategies utilize biodegradable polymeric matrices alone or in combination with cells and factors to provide mechanical support to bone, while promoting cell proliferation, differentiation, and tissue ingrowth. The performance of mechanically competent, micro‐nanostructured polymeric matrices, in combination with bone marrow stromal cells (BMSCs), is evaluated in a critical sized bone defect. Cellulose acetate (CA) is used to fabricate a porous microstructured matrix. Type I collagen is then allowed to self‐assemble on these microstructures to create a natural polymer‐based, micro‐nanostructured matrix (CAc). Poly (lactic‐co‐glycolic acid) matrices with identical microstructures serve as controls. Significantly higher number of implanted host cells are distributed in the natural polymer based micro‐nanostructures with greater bone density and more uniform cell distribution. Additionally, a twofold increase in collagen content is observed with natural polymer based scaffolds. This study establishes the benefits of natural polymer derived micro‐nanostructures in combination with donor derived BMSCs to repair and regenerate critical sized bone defects. Natural polymer based materials with mechanically competent micro‐nanostructures may serve as an alternative material platform for bone regeneration.     

A collagen(Col)/nano-hydroxyapatite (nHA) biological composite bone scaffold with double multi-level interface reinforcement

IntroductionBone scaffold is expected to possess excellent mechanical and biological properties similar to natural bone tissues. In this study, we aimed to prepare a biomineralized Col and hydroxyapatite composite scaffold consisting of biomimetic bone components and multi-level bionic bone structure to strengthen its mechanical properties.MethodsWe prepared a Col/nano-hydroxyapatite biological composite scaffold with multi-level structure (from nanofibers to micron bionic bone motif to bionc bone scaffold) of biomimetic bone tissue, and biomineralized the scaffold in simulated body fluid (SBF) preheated to 37 °C. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and Scanning electron microscope, were used to characterize the biomineralized products.ResultsMorphological study confirmed in situ deposition of nHA in the multi-scale hierarchical structure of the biomineralized scaffold. We explored the biomineralization nucleation mechanism of the scaffolds at the atomic level based on the first principles and the mechanisms for growth of mineralized nHA crystal array in its multi-scale structure, and how the double multiscales structure strengthened the mechanical properties of the material.ConclusionsThis synthetic bone scaffold, with bionic bone composition and double multi-level interface reinforcement, provides a new strategy for synthesizing bioactive bone scaffolds with enhanced biomechanical properties.     

Carbon nanotubes reinforced with natural/synthetic polymers to mimic the extracellular matrices of bone – a review

The persistent failure of conventional materials used in manufacturing orthopedic implants was due to the deficiency or poor integrations of implant materials to the juxtaposed bone and stress-strain imbalances between the interfaces of tissues and implant materials. Therefore, the fabrication of a suitable bioactive scaffold for bone tissue engineering is considered a vital requisite to mimic the extracellular bone matrix. Numerous researches were reported concerning the fabrication of a suitable bioactive scaffold to improve cell adhesion, proliferation, and differentiation so far. However, for the past two decades, the research on carbon nanotubes (CNTs)-reinforced composites employed in the biomedical field is increasing day-by-day because of its outstanding properties. Moreover, it is essential to choose a biocompatible polymer with greater affinity to act as an extracellular matrix as well as to attract CNTs and in facilitating the homogeneous distribution of CNTs in aqueous and organic solvents. The development of CNTs-based composites in bone tissue engineering is presented in this review based on the last 10 years of research. The detailed information about the structural-functions and defects of bone, and the importance of CNTs-functionalized natural and synthetic polymers, and their potential activity in bone regenerations and bone replacements have been reviewed.     

Synthesis and characterization of poly(d,l-lactide-co-glycolide) modified by maleic anhydride and 1,4-butanediamine

Bone tissue engineering is sought to apply strategies for bone defects healing biodegradable porous scaffolds without limitations and shortcomings. In this work, we have developed a novel maleic anhydride (MAH) and 1,4-butanediamine modified poly(lactide-co-glycolide) polymer (BMPLGA). The synthesized polymer was characterized by Fourier transform infrared spectrometry (FTIR), Nuclear magnetic resonance spectra (¹H NMR), gel permeation chromatography (GPC) and contact angle measurements. In addition, cell morphologies in the extracts and cell cytotoxity were also studied. The results showed that the BMPLGA was successfully obtained by introducing MAH and 1,4-butanediamine into PLGA in bulk. The introduction of anhydride and amino groups improved the hydrophilicity of PLGA. Fibroblastic cells showed normal morphologies in BMPLGA extracts, and the BMPLGA materials showed no cell cytotoxicity. The synthetic BMPLGA material may have potentials for biomedical applications due to improving hydrophilicity.     

Hydrogels as Scaffolds in Bone-Related Tissue Engineering and Regeneration

Several years have passed since the medical and scientific communities leaned toward tissue engineering as the most promising field to aid bone diseases and defects resulting from degenerative conditions or trauma. Owing to their histocompatibility and non-immunogenicity, bone grafts, precisely autografts, have long been the gold standard in bone tissue therapies. However, due to issues associated with grafting, especially the surgical risks and soaring prices of the procedures, alternatives are being extensively sought and researched. Fibrous and non-fibrous materials, synthetic substitutes, or cell-based products are just a few examples of research directions explored as potential solutions. A very promising subgroup of these replacements involves hydrogels. Biomaterials resembling the bone extracellular matrix and therefore acting as 3D scaffolds, providing the appropriate mechanical support and basis for cell growth and tissue regeneration. Additional possibility of using various stimuli in the form of growth factors, cells, etc., within the hydrogel structure, extends their use as bioactive agent delivery platforms and acts in favor of their further directed development. The aim of this review is to bring the reader closer to the fascinating subject of hydrogel scaffolds and present the potential of these materials, applied in bone and cartilage tissue engineering and regeneration.     

The Use of Bone Substitutes in the Treatment of Bone Defects – the Clinical View and History

Summary: Bone has the ability to regenerate and remodel itself. In the clinic circumstances appear when bone defects do not heal spontaneously. These situations frequently result from trauma, congenital abnormities, infection or tumor resection. Hence, filling of the resulting defect by bone transplantation is a common practise with an increasing value in the re-establishment of the musculoskeletal system to promote bone healing. Since decades, efforts have been put to improve the effectiveness of bone substitutes. Conventional approaches with the use of ivory, animal and also human bone were not satisfactory. Negative effects like allergic reactions, rejection reactions, inflammations and other problems occurred. These led to implant failure, non union and amputation, to only mention a few. The introduction of bone banks and the development of standards in bone transplantation brought up the false hope to find a final solution for the treatment of bone loss. Disease transmissions (HIV) by allografts caused critical discussions. Despite all efforts, transplantation of autogenous cancellous bone is still the “gold standard” to induce bone healing. However, autografts are only limited available and are accompanied with high morbidity and mortality during the harvest. The problems associated with autologous and allogenous bone grafts promoted the development of multiple organic and inorganic bone substitutes. Well established substitutes at the present are demineralised bone matrix (DBM), composites and calcium phosphates (hydroxyl apatite and tri-calcium phosphate). These osteoconductive substances have shown to improve new bone formation. Nevertheless, clinical application of these materials is merely successful in a good bony environment but does not induce large progress in critical bone defects.     

In Vivo Biological Behavior of Polymer Scaffolds of Natural Origin in the Bone Repair Process

Autologous bone grafts, used mainly in extensive bone loss, are considered the gold standard treatment in regenerative medicine, but still have limitations mainly in relation to the amount of bone available, donor area, morbidity and creation of additional surgical area. This fact encourages tissue engineering in relation to the need to develop new biomaterials, from sources other than the individual himself. Therefore, the present study aimed to investigate the effects of an elastin and collagen matrix on the bone repair process in critical size defects in rat calvaria. The animals (Wistar rats, n = 30) were submitted to a surgical procedure to create the bone defect and were divided into three groups: Control Group (CG, n = 10), defects filled with blood clot; E24/37 Group (E24/37, n = 10), defects filled with bovine elastin matrix hydrolyzed for 24 h at 37 °C and C24/25 Group (C24/25, n = 10), defects filled with porcine collagen matrix hydrolyzed for 24 h at 25 °C. Macroscopic and radiographic analyses demonstrated the absence of inflammatory signs and infection. Microtomographical 2D and 3D images showed centripetal bone growth and restricted margins of the bone defect. Histologically, the images confirmed the pattern of bone deposition at the margins of the remaining bone and without complete closure by bone tissue. In the morphometric analysis, the groups E24/37 and C24/25 (13.68 ± 1.44; 53.20 ± 4.47, respectively) showed statistically significant differences in relation to the CG (5.86 ± 2.87). It was concluded that the matrices used as scaffolds are biocompatible and increase the formation of new bone in a critical size defect, with greater formation in the polymer derived from the intestinal serous layer of porcine origin (C24/25).     

Hydroxyapatite For Poly(α-Hydroxy Esters) Biocomposites Applications

This article focuses on providing a systematic review on various fundamental properties of composite based on poly(α-hydroxy esters) and hydroxyapatite (HAp) for application in bone tissue engineering. Poly(α-hydroxy esters), a well-known synthetic biopolymer has attracted considerable interest to be employed for synthesis of bone graft substitute material with HAp mainly due to its bioresorbability, variable biodegradation rate and melt-processibility. Such features are simultaneously attractive for both biomedical application and industrial-scale productions. Besides the main function of hydroxyapatite as bioactive ceramic filler in composite to induce new bone formation upon polymer bioresorption, HAp can also serve as reinforcement for matrix polymer by providing sufficient mechanical support for cell attachment. Moreover, HAp plays a significant role in determining other composite properties, such as resistance to ingress of body fluid, body temperature ageing, relaxation movement of polymer segment, and in vivo biodegradation. These properties constitute as the fundamental requirements in field of bone tissue regeneration which is desirable to be achieved by unique composite system based on poly(α-hydroxyesters) and HAp particles.     

Polymer nanocomposites in medicine

A large number of recent studies deal with the application of nano materials to different medicine areas, application that led to a new discipline known as nanomedicine. It comprises the processes of diagnosing, treating, curing, preventing diseases and also dealing with traumatic injury, relieving pain and preserving/improving human health by using nano materials. Among nano materials, an important place belongs to the group of natural and synthetic polymer nanocomposites. These are made up of an organic polymer matrix and a mineral, organic or metallic nanofiller. The properties of polymer nanocomposites depend on the characteristics of the components and on the interaction polymer-nanofiller. Polymer nanocomposites offer to modern medicine new opportunities for generate products for antibacterial treatment, tissues engineering, cancer therapy, medical imaging, dental applications, drug delivery, etc.     

仿生矿化的机理和应用研究进展

碳酸钙、磷酸钙为代表的生物矿物广泛分布于自然界中,经过不同的矿化过程,在生物体内呈现出多样的结构、形貌和功能,构成生物体多种组织和器官.在人工材料合成领域,仿生矿化通过调控碳酸钙、磷酸钙等矿物的成核与生长,获得具有复杂高级结构和特殊生物功能的无机或无机/有机复合材料.本文重点介绍仿生矿化机理和应用的最近研究进展,包括仿...     

Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments

After tooth loss, bone resorption is irreversible, leaving the area without adequate bone volume for successful implant treatment. Bone grafting is the only solution to reverse dental bone loss and is a well-accepted procedure required in one in every four dental implants. Research and development in materials, design and fabrication technologies have expanded over the years to achieve successful and long-lasting dental implants for tooth substitution. This review will critically present the various dental bone graft and substitute materials that have been used to achieve a successful dental implant. The article also reviews the properties of dental bone grafts and various dental bone substitutes that have been studied or are currently available commercially. The various classifications of bone grafts and substitutes, including natural and synthetic materials, are critically presented, and available commercial products in each category are discussed. Different bone substitute materials, including metals, ceramics, polymers, or their combinations, and their chemical, physical, and biocompatibility properties are explored. Limitations of the available materials are presented, and areas which require further research and development are highlighted. Tissue engineering hybrid constructions with enhanced bone regeneration ability, such as cell-based or growth factor-based bone substitutes, are discussed as an emerging area of development.     

聚合物互通多孔材料的乳液模板法制备及其功能化研究*

本文对近年来利用乳液模板制备聚合物互通多孔材料的研究进行了综述,主要介绍以高内相乳液模板制备互通多孔聚合物整体柱和利用双重乳液 (或称多重乳液) 制备多孔或多空聚合物微球的进展;分析目前多孔聚合物材料研究中存在的问题及其研究动态;讨论合成多孔聚合物材料的性能缺陷及其表面功能化改性的相关研究;并对聚合物互通多孔材料潜在的应用和研究前景进行了展望。     

骨组织工程支架材料研究进展*

骨在组织工程中得到了非常广泛、深入的研究.支架材料与许多可降解材料一起也在进行探索性研究.用于骨组织工程的生物材料可以是三维多孔的刚硬材料,也可以是可注射材料.本文从聚合物角度综述了骨组织工程对支架材料的基本要求,用于骨组织工程的可降解生物材料、支架材料的设计和制备技术以及支架材料的表面修饰等方面的研究进展.     

Nano‐Star‐Shaped Polymers for Drug Delivery Applications

With the advancement of polymer engineering, complex star‐shaped polymer architectures can be synthesized with ease, bringing about a host of unique properties and applications. The polymer arms can be functionalized with different chemical groups to fine‐tune the response behavior or be endowed with targeting ligands or stimuli responsive moieties to control its physicochemical behavior and self‐organization in solution. Rheological properties of these solutions can be modulated, which also facilitates the control of the diffusion of the drug from these star‐based nanocarriers. However, these star‐shaped polymers designed for drug delivery are still in a very early stage of development. Due to the sheer diversity of macromolecules that can take on the star architectures and the various combinations of functional groups that can be cross‐linked together, there remain many structure–property relationships which have yet to be fully established. This review aims to provide an introductory perspective on the basic synthetic methods of star‐shaped polymers, the properties which can be controlled by the unique architecture, and also recent advances in drug delivery applications related to these star candidates.     

Improved survival of cardiac cells on surface modified electrospun nanofibers

Polycaprolactone (PCL) is a popular synthetic polymer used in the field of cardiac tissue engineering (CTE) due to its non-toxic degraded by products and low cost manufacturing method. However, hydrophobic nature of this material limits its wide spread application in different cell interaction processes. Therefore, current study aims to chemically modify PCL made random and aligned nanofibers with collagen coating mimicking the oriented matrix of the cardiac cells. Morphological and chemical properties of the electrospun PCL nanofibers were evaluated by SEM, FTIR, XRD and water contact angle measurement. Results indicated that the anisotropic characteristics of aligned nanofibers promoted cell attachment and alignment, which closely match the requirements of native cardiac cells. Thus, aligned nanofibers could be preferred for cardiac tissue regeneration and defects over random nanofibers.     

有机-无机杂化骨修复材料

寻找理想的骨修复材料一直是骨科领域的研究热点之一。骨修复材料已由最初单纯取代天然骨组织的惰性材料向具有诱导骨组织再生功能的生物活性材料发展,其中有机-无机杂化材料由于有机和无机组分在分子/纳米水平的复合使其能够最大程度地实现二者的优势互补和协同优化,近年来受到广泛关注。本文着重介绍了有机-无机杂化骨修复材料近些年来的研究进展,并对其发展趋势进行了展望。     

Designing Gelatin Based Blood Compatible Materials with Hydrophilic and Hydrophobic Macromolecular Chains

Polymer matrices based on poly 2-hydroxyethyl methacrylate (PHEMA) have emerged as promising materials for developing applications in biomedical and tissue engineering fields. The major criteria of a material to be used as a support matrix in tissue engineering application rests on its biocompatible, hydrophilic, and mechanically strong nature. Although a great deal of research efforts have been put into designing such materials, achieving these properties together for such a material still remains a challenge. Thus, by a judicious combination of natural and synthetic polymers, such as gelatin and copolymers of PHEMA and PAN, respectively, it has been attempted to synthesize a polymer material by redox polymerization method. The prepared polymer matrix was characterized by FTIR, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) techniques. The prepared polymeric biomaterials were assessed for their water sorption potential under varying experimental conditions such as chemical composition, pH, and temperature of the swelling bath. The diffusion mechanism of transport of water molecules arising due to solvent–polymer interaction was analyzed to predict the behavior of continuously relaxing macromolecular chains. The in vitro blood compatibility of the prepared polymeric materials was determined by methods such as blood clot formation, platelet adhesion, percent hemolysis assay, and protein–adsorption on the surface of the prepared biomaterials.     

Clinical Application of Resorbable Polymers in Guided Bone Regeneration

Summary : Guided bone regeneration was shown to be successful in vitro and in vivo using resorbable or nonresorbable materials. Resorbable material has the advantage of progressive substitution by bone. Resorbable polymers of ∝-hydroxy acids like polylactide or polyglycolide are commonly used for tissue engineering and in guided bone regeneration. In clinical studies, guided bone regeneration was successful in non-weight bearing bone, e.g. in dental surgery and craniofacial surgery. This paper reports the preliminary result of using resorbable poly(L/DL-lactide) 80/20% scaffolds in weight bearing bone with infected large segmental defects as well as in small bony defects of hand due to benign tumour, bone graft donor sites and as an adjunct for joint fusion. Resorbable polylactide implants were used in the form of membranes, large 3-D sponges, chips or as injectable paste. Implants were impregnated with marrow blood to add an osteoinductive component. Long-term follow up revealed that these implants are promising candidates for bone graft substitutes.     

Magnesium-containing silk fibroin/polycaprolactone electrospun nanofibrous scaffolds for accelerating bone regeneration

Bone tissue engineering has become one of the most effective methods for treating bone defects. In this study, an electrospun tissue engineering membrane containing magnesium was successfully fabricated by incorporating magnesium oxide (MgO) nanoparticles into silk fibroin and polycaprolactone (SF/PCL)-blend scaffolds. The release kinetics of Mg²⁺ and the effects of magnesium on scaffold morphology, and cellular behavior were investigated. The obtained Mg-functionalized nanofibrous scaffolds displayed controlled release of Mg²⁺, satisfactory biocompatibility and osteogenic capability. The in vivo implantation of magnesium-containing electrospun nanofibrous membrane in a rat calvarial defect resulted in the significant enhancement of bone regeneration twelve weeks post-surgery. This work represents a valuable strategy for fabricating functional magnesium-containing electrospun scaffolds that show potential in craniofacial and orthopedic applications.     

无机材料的仿生合成

生物矿化重要的特征之一是细胞分泌的有机基质调制无机矿物的成核和生长, 形成具有特殊组装方式和多级结构特点的生物矿化材料(如骨、牙和贝壳)。仿生合成就是将生物矿化的机理引入无机材料合成, 以有机物的组装体为模板, 去控制无机物的形成,制备具有独特显微结构特点的无机材料, 使材料具有优异的物理和化学性能。仿生合成已成为无机材料化学的研究前沿。本文综述了无机材料仿生合成的发展现状。