An overview of nano-polymers for orthopedic applications

This review paper presents many exciting nanotechnology and tissue engineering approaches involving polymers that have enormous potential impact on human health care, particularly for orthopedic applications. As scaffolds play a vital role in tissue engineering, the feasibility of designing polymeric nano-featured scaffolds is reviewed. Although bone is a very diverse tissue providing different functions within the body, recent work has resulted in new biomaterials with promise to solve orthopedic problems. Significant advancements in orthopedic care are required since recent data highlight a less than 15 year lifetime of current hip implants. Nanotechnology (or the use of nanomaterials) is providing a wide range of new materials to improve the current short lifetimes of orthopedic implants.     

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.     

Particle-collision and porogen-leaching technique to fabricate polymeric porous scaffolds with microscale roughness of interior surfaces

A facile technique is herein reported to fabricate three-dimensional(3D) polymeric porous scaffolds with interior surfaces of a topographic microstructure favorable for cell adhesion.As demonstration,a well-known biodegradable polymer poly(lactide-co-glycolide)(PLGA) was employed as matrix.Under the porogen-leaching strategy,the large and soft porogens of paraffin were modified by colliding with small and hard salt particles,which generated micropits on the surfaces of paraffin spheres.The eventual PLGA scaffolds after leaching the modified porogens had thus interior surfaces of microscale roughness imprinted by those micropits.The microrough scaffolds were confirmed to benefit adhesion of bone marrow stromal cells(BMSCs) of rats and meanwhile not to hamper the proliferation and osteogenic differentiation of the cells.The insight and technique might be helpful for biomaterial designing in tissue engineering and regenerative medicine.     

Synthesis and electrospinning of ε-polycaprolactone-bioactive glass hybrid biomaterials via a sol-gel process

Strategies of bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix (ECM) as templates onto which cells attach, multiply, migrate, and function. For this purpose, hybrid biomaterials based on smart combinations of biodegradable polymers and bioactive glasses (BGs) are of particular interest, since they exhibit tailored physical, biological, and mechanical properties, as well as predictable degradation behavior. In this study, hybrid biomaterials with different organic-inorganic ratios were successfully synthesized via a sol-gel process. Poly(ε-caprolactone) (PCL) and tertiary bioactive glass (BG) with a glass composition of 70 mol % SiO(2), 26 mol % CaO, and 4 mol % of P(2)O(5) were used as the polymer and inorganic phases, respectively. The polymer chains were successfully introduced into the inorganic sol while the networks were formed. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analyses (TGA), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) were used to investigate the presence of different chemical groups, structural crystallinity, thermal property, elemental composition, and homogeneity of the synthesized hybrid biomaterials. Identification of chemical groups and the presence of molecular interaction by hydrogen bonding between the organic and inorganic phases was confirmed by FTIR. The XRD patterns showed that all PCL/BG hybrids (up to 60% polymer content) were amorphous. The TGA study revealed that the PCL/BG hybrid biomaterials were thermally stable, and good agreement was observed between the experimental and theoretical organic-inorganic ratios. The SEM/EDX results also revealed a homogeneous elemental distribution and demonstrated the successful incorporation of all the elements in the hybrid system. Finally, these synthesized hybrid biomaterials were successfully electrospun into 3D scaffolds. The resultant fibers have potential use as scaffolds for bone regeneration.     

Alginate hydrogels as biomaterials

[Image: see text] Alginate hydrogels are proving to have a wide applicability as biomaterials. They have been used as scaffolds for tissue engineering, as delivery vehicles for drugs, and as model extracellular matrices for basic biological studies. These applications require tight control of a number of material properties including mechanical stiffness, swelling, degradation, cell attachment, and binding or release of bioactive molecules. Control over these properties can be achieved by chemical or physical modifications of the polysaccharide itself or the gels formed from alginate. The utility of these modified alginate gels as biomaterials has been demonstrated in a number of in vitro and in vivo studies.Micro-CT images of bone-like constructs that result from transplantation of osteoblasts on gels that degrade over a time frame of several months leading to improved bone formation.     

Fabrication and Properties of Polycaprolactone Composites Containing Calcium Phosphate-Based Ceramics and Bioactive Glasses in Bone Tissue Engineering: A Review

Polycaprolactone (PCL) is a bioresorbable and biocompatible polymer that has been widely used in long-term implants and controlled drug release applications. However, when it comes to tissue engineering, PCL suffers from some shortcomings such as slow degradation rate, poor mechanical properties, and low cell adhesion. The incorporation of calcium phosphate-based ceramics and bioactive glasses into PCL has yielded a class of hybrid biomaterials with remarkably improved mechanical properties, controllable degradation rates, and enhanced bioactivity that are suitable for bone tissue engineering. This review presents a comprehensive study on recent advances in the fabrication and properties of PCL-based composite scaffolds containing calcium phosphate-based ceramics and bioglasses in terms of porosity, degradation rate, mechanical properties, in vitro and in vivo biocompatibility and bioactivity for bone regeneration applications. The fabrication routes range from traditional methods such as solvent casting and particulate leaching to novel approaches including solid free-form techniques.     

生物材料表面性能调控骨髓间充质干细胞分化

结合细胞和生物可降解支架的组织工程和再生医学技术为组织、器官的修复和再生提供了一种新途径。骨髓间充质干细胞(BMSCs)具有多向分化潜能,因其取材简单、来源广泛、增殖能力强,无伦理争议,免疫排斥反应小而备受关注。BMSCs在特定区域定向分化成为靶细胞是干细胞治疗的一个重要前提,尤其受到生物材料表面正负电荷、亲疏水和不同的拓扑结构的影响。材料表面涂层蛋白或接枝多肽能够促进BMSCs的分化能力,而生物材料不同的机械性能、几何形状也会影响BMSCs的分化方向。本文综述了近期生物材料调控BMSCs分化的研究结果,为基于BMSCs的组织工程和再生医学材料的设计提供借鉴和指导。     

Tofu as excellent scaffolds for potential bone regeneration

Biomimetic scaffolds present the promising potential for bone regeneration. As a natural gel-like traditional food, tofu with porous architecture and proved biological safety indicated a good potential to be a natural scaffold and easy to be improved by surface modification. Hereon, we fabricated the tofubased scaffolds and systematically explored the potential for bone tissue engineering. In addition, the collagen has been introduced by simple coating to further enhance the surface compatibility of the tofubased scaffold in bone regeneration. The results showed that the tofu-based scaffolds possessed good porous structure and cytocompatibility. Notably, the tofu-based scaffolds could improve the expression of osteogenesis-related genes and proteins, leading to better bone regeneration after 2 months of implantation. All the results indicated that tofu would become an outstanding sustainable natural porous scaffold for bone regeneration with excellent bioactivities.     

Tofu as excellent scaffolds for potential bone regeneration

Biomimetic scaffolds present the promising potential for bone regeneration. As a natural gel-like traditional food, tofu with porous architecture and proved biological safety indicated a good potential to be a natural scaffold and easy to be improved by surface modification. Hereon, we fabricated the tofu-based scaffolds and systematically explored the potential for bone tissue engineering. In addition, the collagen has been introduced by simple coating to further enhance the surface compatibility of the tofu-based scaffold in bone regeneration. The results showed that the tofu-based scaffolds possessed good porous structure and cytocompatibility. Notably, the tofu-based scaffolds could improve the expression of osteogenesis-related genes and proteins, leading to better bone regeneration after 2 months of implantation. All the results indicated that tofu would become an outstanding sustainable natural porous scaffold for bone regeneration with excellent bioactivities.     

Osteogenesis of Osteoblast Seeded Polyurethane-Hydroxyapatite Scaffolds in Nude Mice

Summary: Biodegradable porous polyurethane (PU) scaffolds were used in a tissue engineering approach to create new bone. Two groups of elastomeric bioresorbable PU disks were seeded with osteoblasts and implanted into nude mice. One group had disks of pure PU while the other group had disks of PU- hydroxyapatite composite (PU-HA). After 5 weeks both groups showed radiographic and histologic evidence of significant bone formation. As the new bone formed it replaced the PU scaffolds. Although not statistically significant, there was a trend toward more bone formation in the PU-HA group. Bioresorbable PU shows promise for use in bone tissue engineering.     

Design Parameters of Tissue‐Engineering Scaffolds at the Atomic Scale

Stem‐cell behavior is regulated by the material properties of the surrounding extracellular matrix, which has important implications for the design of tissue‐engineering scaffolds. However, our understanding of the material properties of stem‐cell scaffolds is limited to nanoscopic‐to‐macroscopic length scales. Herein, a solid‐state NMR approach is presented that provides atomic‐scale information on complex stem‐cell substrates at near physiological conditions and at natural isotope abundance. Using self‐assembled peptidic scaffolds designed for nervous‐tissue regeneration, we show at atomic scale how scaffold‐assembly degree, mechanics, and homogeneity correlate with favorable stem cell behavior. Integration of solid‐state NMR data with molecular dynamics simulations reveals a highly ordered fibrillar structure as the most favorable stem‐cell scaffold. This could improve the design of tissue‐engineering scaffolds and other self‐assembled biomaterials.     

Viscoelastic properties of poly(ε‐caprolactone) – hydroxyapatite micro‐ and nano‐composites

Various composites have been proposed in the literature for the fabrication of bioscaffolds for bone tissue engineering. These materials include poly(ε‐caprolactone) (PCL) with hydroxyapatite (HA). Since the biomaterial acts as the medium that transfers mechanical signals from the body to the cells, the fundamental properties of the biomaterials should be characterized. Furthermore, in order to control the processing of these materials into scaffolds, the characterization of the fundamental properties is also necessary. In this study, the physical, thermal, mechanical, and viscoelastic properties of the PCL‐HA micro‐ and nano‐composites were characterized. Although the addition of filler particles increased the compressive modulus by up to 450%, the thermal and viscoelastic properties were unaffected. Furthermore, although the presence of water plasticized the polymer, the viscoelastic behavior was only minimally affected. Testing the composites under various conditions showed that the addition of HA can strengthen PCL without changing its viscoelastic response. The results found in this study can be used to further understand and approximate the time‐dependent behavior of scaffolds for bone tissue engineering. Copyright © 2012 John Wiley & Sons, Ltd.     

In vitro and in vivo evaluation of silk fibroin-hardystonite-gentamicin nanofibrous scaffold for tissue engineering applications

Designing advanced biomaterials with regenerative and drug delivering functionalities remains a challenge in the field of tissue engineering. In this paper we present the design, development, and a use case of an electrospun nano-biocomposite scaffold composed of silk fibroin (SF), hardystonite (HT), and gentamicin (GEN). The fabricated SF nanofiber scaffolds provide mechanical support while HT acts as a bioactive and drug carrier, on which GEN is loaded as an antibacterial agent. Antibacterial zone of inhibition (ZOI) results indicate that the inclusion of 3–6 wt% GEN significantly improves the antibacterial performance of the scaffolds against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria, with an initial burst release of 10–20% and 72–85% total release over 7 days. The release rate of stimulatory silicon ions from SF-HT scaffolds reached 94.53±5 ppm after 7 days. Cell studies using osteoblasts show that the addition of HT significantly improved the cytocompatibility of the scaffolds. Angiogenesis, in vivo biocompatibility, tissue vascularization, and translatability of the scaffolds were studied via subcutaneous implantation in a rodent model over 4-weeks. When implanted subcutaneously, the GEN-loaded scaffold promoted angiogenesis and collagen formation, which suggests that the scaffold may be highly beneficial for further bone tissue engineering applications.     

Synthesising injectable molecular self-curing polymer from monomer derived from lignocellulosic oil palm empty fruit bunch biomass: A review on treating Osteoarthritis

Osteoarthritis (OA) is a chronic and irreversible degenerative joint disease that most commonly affects individuals in their forties and fifties worldwide due to the continuously increasing life expectancy. Although joint replacement is an effective remedy for severe end-stage OA, the functional outcomes could be unsatisfactory, while the implants might have a limited lifespan. Due to the drawbacks and limitations of the joint replacement approach, bone Tissue Engineering (TE) is one of the promising bone tissue regeneration technologies that aid in cartilage repair and regeneration and has attracted the attention of experts. The advanced development of biopolymers, in particular biopolymer derived from Oil Palm Empty Fruit Bunch (OPEFB), has been utilised in the fabrication of scaffolds that serve as a crucial component in bone TE. The abundant supply of OPEFB biomass and the increasing trend of converting waste into wealth for environmental sustainability have also provided the opportunity and interest to fully apply biopolymer-derived materials for bone scaffolding and other applications. Therefore, this paper aimed to provide a review of the biopolymers derived from OPEFB for the treatment of OA and other related applications. A brief overview of the biomass sources in Malaysia was presented, followed by a discussion on the chemical compositions and pre-treatment methods of OPEFB by using organosolv pre-treatment and enzymatic hydrolysis for maximum glucose recovery, monomer derived from cellulose OPEFB and synthesizing self-curing polymer scaffold. Additionally, a detailed review of the polymeric biomaterials in bone TE for the fabrication of scaffolds were included in this review. Most importantly, the paper described the potential use of injectable polymeric biomaterials that provide a significant benefit in orthopaedic applications. Overall, this paper provides a perspective on the potential of OPEFB-derived injectable scaffolds as an alternative OA treatment and future bone TE applications.     

Advances in Polymeric Systems for Tissue Engineering and Biomedical Applications

The characteristics of tissue engineered scaffolds are major concerns in the quest to fabricate ideal scaffolds for tissue engineering applications. The polymer scaffolds employed for tissue engineering applications should possess multifunctional properties such as biocompatibility, biodegradability and favorable mechanical properties as it comes in direct contact with the body fluids in vivo. Additionally, the polymer system should also possess biomimetic architecture and should support stem cell adhesion, proliferation and differentiation. As the progress in polymer technology continues, polymeric biomaterials have taken characteristics more closely related to that desired for tissue engineering and clinical needs. Stimuli responsive polymers also termed as smart biomaterials respond to stimuli such as pH, temperature, enzyme, antigen, glucose and electrical stimuli that are inherently present in living systems. This review highlights the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers have also been discussed. The ultimate objective is to emphasize on these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications.

     

Natural lotus root-based scaffolds for bone regeneration

A high incidence of bone defects and the limitation of autologous bone grafting require 3 D scaffolds for bone repair. Compared with synthetic materials, natural edible materials possess outstanding advantages in terms of biocompatibility, bioactivities and low manufacturing cost for bone tissue engineering. In this work, attracted by the natural porous/fabric structure, good biocompatibility and bioactivities of the lotus root, the lotus root-based scaffolds were fabricated and investigated the...     

Novel physically crosslinked polyurethane-block-poly(vinyl pyrrolidone) hydrogel biomaterials

Successful tissue repair and regeneration relies on the design of new biomaterials that can mediate cell interaction without inflicting undesirable responses. Novel physically crosslinked polyurethane-block-poly(vinyl pyrrolidone) hydrogel biomaterials were synthesized by the macroiniferter controlled radical polymerization method. The structures of the hydrogels were studied by FT-IR and (1)H NMR. Hydrogels with EWC up to 37 wt.-% were prepared. The presence of the PVP block significantly increased the hard-segment glass transition temperature. Vascular smooth muscle cell attachment and spreading on the hydrogels indicated that these materials have a potential for use as scaffolds in tissue engineering.     

Porous scaffolds based on cross-linking of poly(L-glutamic acid)

Porous scaffolds based on water-soluble PLGA and CS were prepared. The pores were verified to be alveolate, uniform and continuous. The effects of freezing temperature, freeze-drying time, solid content and molecular weight of reactants on the pore structure of the scaffolds were studied. The scaffold morphology could be adjusted by changing the freezing temperature and solid content of reacting polymer. Their degradation rate can be adjusted by changing the proportion of PLGA and CS. The porosity of scaffolds was higher than 90% and the high swelling ratio showed that these scaffolds had excellent hydrophilic performance. The in vitro culture of chondrocytes indicates that the obtained PLGA/CS porous scaffolds are very promising biomaterials for tissue engineering applications.     

Evaluation of 3D Printed Gelatin‐Based Scaffolds with Varying Pore Size for MSC‐Based Adipose Tissue Engineering

Adipose tissue engineering aims to provide solutions to patients who require tissue reconstruction following mastectomies or other soft tissue trauma. Mesenchymal stromal cells (MSCs) robustly differentiate into the adipogenic lineage and are attractive candidates for adipose tissue engineering. This work investigates whether pore size modulates adipogenic differentiation of MSCs toward identifying optimal scaffold pore size and whether pore size modulates spatial infiltration of adipogenically differentiated cells. To assess this, extrusion‐based 3D printing is used to fabricate photo‐crosslinkable gelatin‐based scaffolds with pore sizes in the range of 200–600 µm. The adipogenic differentiation of MSCs seeded onto these scaffolds is evaluated and robust lipid droplet formation is observed across all scaffold groups as early as after day 6 of culture. Expression of adipogenic genes on scaffolds increases significantly over time, compared to TCP controls. Furthermore, it is found that the spatial distribution of cells is dependent on the scaffold pore size, with larger pores leading to a more uniform spatial distribution of adipogenically differentiated cells. Overall, these data provide first insights into the role of scaffold pore size on MSC‐based adipogenic differentiation and contribute toward the rational design of biomaterials for adipose tissue engineering in 3D volumetric spaces.     

Electrospinning nanofibers of microbial polyhydroxyalkanoates for applications in medical tissue engineering

Differently to most chemically synthesized medical materials, polyhydroxyalkanoates (PHAs) are intracellular carbon and energy storage granules, which is a family of natural bio-polymers synthesized by microorganism's materials. Due to excellent biocompatibility reasonable biodegradability and versatile material difference, PHAs are well medical biomaterials candidates for applications in tissue engineering and drug delivery, including commercial PHB, PHBV, PHBHHx, PHBVHHx, P34HB and few uncommercial PHAs. Electrospinning nanofibers with the size of 10–10,000 nm can improve the mechanical properties and decrease the crystallinity of PHA, meanwhile simulate the structure and function of native extracellular matrix of cells. Hence, PHAs electrospinning nanofibers as engineered scaffolds have been widely used for tissue engineering scaffolds in cardiovascular, vascular, nerve, bone, cartilage and skin; also, as carriers for application in drug delivery system. In this review, we highlight the extraction and properties of medical PHAs from natural or engineered microorganism, and microstructure, current manufacturing techniques and medical applications of electrospinning nanofibers of PHAs. Moreover, the current challenges and prospects of PHAs electrospinning nanofibers are discussed rationally, providing an insight into developing vibrant fields of PHAs electrospinning nanofibers-based biomedicine.