Current advances concerning the most cited metal ions doped bioceramics and silicate-based bioactive glasses for bone tissue engineering

Studies related to biomaterials that stimulate the repair of living tissue have increased considerably, improving the quality of many people's lives that require surgery due to traumatic accidents, bone diseases, bone defects, and reconstructions. Among these biomaterials, bioceramics and bioactive glasses (BGs) have proved to be suitable for coating materials, cement, scaffolds, and nanoparticles, once they present good biocompatibility and degradability, able to generate osteoconduction on the surrounding tissue. However, the role of biomaterials in hard tissue engineering is not restricted to a structural replacement or for guiding tissue regeneration. Nowadays, it is expected that biomaterials develop a multifunctional role when implanted, orchestrating the process of tissue regeneration and providing to the body the capacity to heal itself. In this way, the incorporation of specific metal ions in bioceramics and BGs structure, including magnesium, silver, strontium, lithium, copper, iron, zinc, cobalt, and manganese are currently receiving enhanced interest as biomaterials for biomedical applications. When an ion is incorporated into the bioceramic structure, a new category of material is created, which has several unique properties that overcome the disadvantages of primitive material and favors its use in different biomedical applications. The doping can enhance handling properties, angiogenic and osteogenic performance, and antimicrobial activity. Therefore, this review aims to summarize the effect of selected metal ion dopants into bioceramics and silicate-based BGs in bone tissue engineering. Furthermore, new applications for doped bioceramics and BGs are highlighted, including cancer treatment and drug delivery.     

Fabrication and evaluation of nanofibrous polyhydroxybutyrate valerate scaffolds containing hydroxyapatite particles for bone tissue engineering

Tissue engineering is a new approach for regeneration of damaged tissues. The current clinical methods such as autograft and allograft transplantation are not effective for repairing bone damages, mainly due to the limited available sources and the donor-site side effects. In this research, the nanocomposite poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/nano hydroxyapatite (nHA) scaffolds with different nHA ratios for bone regeneration were utilized. The diameter and porosity of scaffolds were approximately 200?nm and 74%, respectively. The degradability test of the scaffolds suggests a low degradation rate with total degradation of 30% after 3 months. Cytotoxicity result showed that cultured osteoblast cells (MC3T3) on nanocomposite scaffolds had superiority in terms of higher proliferation and attachment in comparison with PHBV scaffold. The protein expression of alkaline phosphatase illustrated that nanofibrous scaffold containing hydroxyapatite had the highest alkaline phosphatase activities as a result of better proliferation. These results recommend that PHBV/nHA scaffolds are suitable candidates for bone tissue engineering.     

A comprehensive review on the preparation and application of calcium hydroxyapatite: A special focus on atomic doping methods for bone tissue engineering

Hydroxyapatite (HAP) has been considered to be one of the most preferred scaffold materials among many in the last decade for the bone tissue engineering. Be it prosthetic implants, scaffolds or artificial bone cement, hydroxyapatite has received highest attraction among all due to its chemical and physical properties similar to that of human bone. Although it can be used in the bone tissue engineering as the original composition; for enhancing its different properties relevant to in vivo applications, the calcium in HAP may also be replaced by other atomic dopants depending on usage. Here, we review various HAP coating agents and methods, their merits and demerits. We also review various HAP doping materials, including both cationic as well as anionic materials. We discuss the effects and usage of substitution of hydroxyapatite and their subsequent usage in both bone tissue engineering and maxillofacial surgeries. We consider various research articles published in recent times to accomplish detailed discussion on the subject.     

Design and characterization of biphasic ferric hydroxyapatite-zincite nanoassembly for bone tissue engineering

Hydroxyapatite (HAp) is one of the most studied biomaterials for orthopaedic applications, yet its commercialization holds in a few of the lags, such as non-antibacterial activity and target deficiency. In this context, we aimed to design a biphasic nanoassembly of Ferric-HAp-Zincite (ZFHAp) via a one-step co-precipitation method. Ferric-HAp obtained Ca_9·333Fe_1·167(PO₄)₇ phase in all the samples, and the secondary phases such as Ca₉Fe(PO₄)₇ and Ca_28·8Fe_3·2(PO₄)₂₁O_0.5 were governed by the Fe dopant concentration. Along with ferric-HAp, zincite phases were present in all the samples depending on the concentration of Zn precursor. The synthesized ZFHAp samples were hexagonal in structure with size <100 nm, and a dual morphology, i.e., rod-shaped (77.8 ± 10 nm; major corresponding to HAp) and particulate shaped (30.9 ± 5 nm; minor due to Zincite). Doping of iron imparted paramagnetism resulting in the magnetic target efficiency. ZFHAp samples showed excellent self-antibacterial activity against clinically significant two Gram-positive (E. hirae, S. aureus) and two Gram-negative (E. coli, S. paratyphi) bacteria with lower MIC values (60–80 μg/ml). The antibacterial mechanism was found to be ROS independent and due to the linear release of Zn²⁺ and Fe³⁺ ions. The designed ZFHAp samples showed no cytotoxicity up to 5 mg/mL and exhibited 3 times higher bone cell proliferation along with the significant Alkaline Phosphatase (ALP) activity. The prepared nanomaterials also did not show any inflammatory response to bone cells. These findings entitle ZFHAp as a potential candidate for orthopaedic as well as other biomedical applications subject to further clinical trials.     

The effects of BaTiO3 on the handleability and mechanical strength of the prepared piezoelectric calcium phosphate silicate for bone tissue engineering

Natural bone is a piezoelectric material that can generate electrical signals when subjected to an external force. Although many studies have attempted to develop piezoelectric biomaterials for bone regeneration, post-treatment steps, such as sintering, are always needed. In this study, we prepared an injectable and piezoelectric bone substitute based on nanosized BaTiO₃ (nBT)-added calcium phosphate silicate (CPS). The impacts of nBT on the CPS handleability and mechanical strength were characterized, and show that adding nBT could improve the CPS handleability but affect the CPS mechanical strength in a concentration-dependent manner (from 25.3 ± 1.0 MPa for 10BC to 13.5 ± 1.0 MPa for 40BC). In addition, our approach could fabricate a piezoelectric bone substitute with comparable piezoelectricity to the native bone without any post-treatment. The in vitro analyses demonstrated that nBT/CPS was biocompatible and could promote osteoblast differentiation. In conclusion, our results strongly indicate that the injectable formulation based on nBT/CPS can be a promising candidate in bone tissue engineering, and further research is needed to investigate the biomaterial's performance in bone defect animal models.     

Stimulations of strontium-doped calcium polyphosphate for bone tissue engineering to protein secretion and mRNA expression of the angiogenic growth factors from endothelial cells in vitro

The vascularization of tissue-engineered bone is the key problem needed solving before application of tissue-engineered bone in clinical practice. Meanwhile, endothelial cells are the major and important source of seed cells in bone tissue engineering, and significant on promoting vascularization in tissue-engineered bone. Vascularization (namely angiogenesis) is a process mainly controlled by several angiogenic growth factors (VEGF, bFGF and MMP-2) which can be secreted by endothelial cells. Therefore, the research on the stimulations of SCPP to the secretion of the angiogenic growth factors from endothelial cells is very important. This study was performed to determine the ability of strontium-doped calcium polyphosphate (SCPP) to induce angiogenesis by detecting the protein secretion levels and mRNA expression of VEGF, bFGF and MMP-2 from cultured endothelial cells. As a control, we also researched the effect of HA on the mRNA expressions and protein secretion of angiogenic growth factors from cultured endothelial cells. We cultured endothelial cells with SCPP scaffolds containing various concentration of strontium and HA. The results obtained in the MTT and SEM tests indicated that endothelial cells on SCPP scaffold exhibited higher proliferation rate and were easy to get a good spread than them on CPP, the best state of growth and proliferation of cells could be observed on 8%SCPP. The results of ELISA demonstrated that the protein levels of VEGF, bFGF and MMP-2 from cultured endothelial cells increased with the increasing Sr doped in calcium polyphosphate in SCPP groups, the peaks appeared on 8%SCPP. All SCPP groups showed a better ability to stimulate the protein secretion of VEGF, bFGF and MMP-2 from endothelial cells relative to CPP group and HA group. The results of RT-PCR suggested that the 8%SCPP group exhibited a significantly higher mRNA expression of VEGF, bFGF and MMP-2 relative to CPP group and HA group. In conclusion, the results of this study demonstrated that 8%SCPP had obvious promotion for secretion and mRNA expression of angiogenic growth factors from cultured endothelial cells.     

Recent trends in bone defect repair and bone tissue regeneration of the two-dimensional material MXene

Bone defects have attracted much attention for a long time and seriously affect the function of the motor system. At present, the application of biological materials and biological scaffolds implanted in the defect site to promote the healing of bone defects is the main treatment method for bone defect repair. In recent years, the emergence of two-dimensional materials has brought new opportunities for biological materials. As a two-dimensional nanomaterial based on ceramics, MXene has unique physical and chemical properties, such as electrical conductivity, hydrophilicity, and antibacterial and photothermal effects, which make it a very broad application prospect in bone defect biomaterials. This review will start from the pathophysiological changes of bone defects and intervention factors of bone defect repair, introduce in detail the preparation and modification methods, physical and chemical properties and biological characteristics of the two-dimensional material MXene, and review the application status and research progress of MXene in bone defect repair and bone tissue regeneration. This provides a reference for the further application of MXene in bone defect repair.     

Creep-resistant dextran-based polyurethane foam as a candidate scaffold for bone tissue engineering: Synthesis,chemico-physical characterization,and in vitro and in vivo biocompatibility

A highly crosslinked composite dextran-based scaffold (named DexFoam) was tailored to overcome specific deficiencies of polymeric and ceramic bone scaffolds and to guarantee a bone-mimicking microenvironment for the proliferation of human mesenchymal stem cells in vitro. The creep resistance for up to 90% compressive stain, the capability to regain the original shape after deformation, and the good thermal stability in both physiological and “body limit” conditions make DexFoam a valid alternative to the currently available bone scaffolds. Histopathological evaluation for host reaction and tissue colonization of DexFoam scaffold, implanted subcutaneously in mice, demonstrated its in vivo biocompatibility and biodegradability.     

Preparation,properties and in vitro cellular response of multi-walled carbon nanotubes/bioactive glass/poly(etheretherketone) biocomposite for bone tissue engineering

Desired bone repair biomaterial must have good biocompatibility and suitable mechanical properties that are equivalent to those of human bones. In this study, multi-walled carbon nanotubes (MWCNTS) was designed to incorporate into bioactive glass/poly(etheretherketone) to fabricate a composite of multi-walled carbon nanotubes/bioactive glass/poly(etheretherketone) (MWCNTS/BG/PEEK) through a compounding and injection-molding process. The microstructures, mechanical properties, thermal stability and bioactivity of the ternary biocomposite, as well as preliminary cell responses of MC3T3-E1 osteoblast cells to this biomaterial, were investigated. The mechanical performance of ternary MWCNTS/BG/PEEK composite was vastly superior to binary BG/PEEK composite. More importantly, cell culture tests showed that cell adhesion, viability and differentiation of MC3T3-E1 cells were significantly promoted on the MWCNTS/BG/PEEK composite. Moreover, it was found that MWCNTS in composite further promoted cell metabolic vitality and osteogenic differentiation of osteoblast cells. Hence, this MWCNTS/BG/PEEK biomaterial may be used as a promising bone graft scaffold in dental and orthopedic applications.     

Nano-hydroxyapatite formation via co-precipitation with chitosan-g-poly(N-isopropylacrylamide) in coil and globule states for tissue engineering application

With the excellent biocompatibility and osteoconductivity, nano-hydroxyapatite (nHA) has shown significant prospect in the biomedical applications. Controlling the size, crystallinity and surface properties of nHA crystals is a critical challenge in the design of HA based biomaterials. With the graft copolymer of chitosan and poly(N-isopropylacrylamide) in coil and globule states as a template respectively, a novel composite from chitosan-g-poly(N-isopropylacrylamide) and nano-hydroxyapatite (CS-g-PNIPAM/nHA) was prepared via co-precipitation. Zeta potential analysis, thermogravimetric analysis and X-ray diffraction were used to identify the formation mechanism of the CS-g-PNIPAM/nHA composite and its morphology was observed by transmission electron microscopy. The results suggested that the physical aggregation states of the template polymer could induce or control the size, crystallinity and morphology of HA crystals in the CS-g-PNIPAM/nHA composite. The CS-g-PNIPAM/nHA composite was then introduced to chitosan-gelatin (CS-Gel) polyelectronic complex and the cytocompatibility of the resulting CS-Gel/composite hybrid film was evaluated. This hybrid film was proved to be favorable for the proliferation of MC 3T3-E1 cells. Therefore, the CS-g-PNIPAM/nHA composite is a potential biomaterial in bone tissue engineering.     

Incorporation of graphene oxide and calcium phosphate in the PCL/PHBV core-shell nanofibers as bone tissue scaffold

Bone tissue scaffolds should have both desired mechanical stability and cell activities including biocompatibility, cell differentiation, and maturation. Also, suitable mineralization is another key factor for these materials. Hence, in current work, in order to achieve a scaffold with desired mechanical and bioactivity properties, core-shell nanofibers based on the polycaprolactone and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) with different concentration of graphene oxide (GO) (0.5, 1, and 1.5 wt%) and calcium phosphate (CP) (1 and 3 wt%) were prepared to utilize as bone scaffold. Microstructure of nanofibers observed by field emission scanning electron microscope (FE-SEM) and results exhibited that the most of nanofibers had 270–500 nm diameter. Attenuated total reflectance Fourier transform infrared spectroscopy and energy dispersive X-ray evaluations verified appearance of GO and CP into the electrospun scaffolds (ES). Transmission electron microscopy analysis endorsed core-shell structure of nanofibers. X-ray diffraction study moreover determination of semicrystalline structure, verified presence of GO and CaPO₄ into the nanofibers. Water contact angle demonstrates that, ES2 and ES3 situated in suitable domain of hydrophilicity. Tensile analysis determined that, ES2, ES3, and ES4 had the highest mechanical properties for use as bone scaffold. Cell viability assessment confirmed biocompatibility of scaffold during 7 days. Alkaline phosphatase and alizarin red staining exhibited maturating and differentiating of osteocytes after 21 days seeding on the scaffolds.     

Fabrication and characterization of electrospun poly‐DL‐lactide (PDLLA) fibrous coatings on 45S5 Bioglass® substrates for bone tissue engineering applications

BACKGROUND: This work focuses on combining electrospun biodegradable poly‐DL‐lactide (PDLLA) fibres and 45S5 Bioglass^® for tissue engineering applications. RESULTS: A variety of fibrous structures were produced upon application of an electric field to a flowing solution of PDLLA (5 wt/v%) in di‐methyl carbonate (DMC). Electrospinning was achieved at an applied voltage of 8.5 kV for a fixed flow rate of 5 µL min^?1. Scanning electron microscopy images of PDLLA fibres deposited on 45S5 Bioglass^® sintered pellets revealed that the fibres had diameters in the range 100–200 nm, leading to increased surface roughness, as assessed by white light interferometry. Bioactivity studies on PDLLA fibre coated Bioglass^® substrates were carried out in simulated body fluid (SBF) for 7, 14 and 28 days. It was found that mineralization of PDLLA fibres on 45S5 Bioglass^® substrate (formation of hydroxyapatite) occurred after 7 days of immersion in SBF and full coverage of PDLLA fibres with HA nanocrystals was achieved after 14 days in SBF. CONCLUSION: The approach investigated represents a convenient method to develop a controlled mineralized fibrous topography on bioactive glass substrates for improved cell attachment, which can be exploited in bone tissue engineering applications. Copyright © 2009 Society of Chemical Industry     

Preparation and characterization of poly(L‐lactide)/ poly(ϵ‐caprolactone) fibrous scaffolds for cartilage tissue engineering

Polyblend fibrous scaffolds in mass ratios of 100/0, 90/10, 80/20, and 70/30 from poly(L ‐lactide) (PLLA) and poly(?‐caprolactone) (PCL) for cartilage tissue engineering were prepared in three steps: gelation, solvent exchanging, and freeze‐drying. Effects of the blend ratio, the exchange medium, and the operating temperature on the morphology of scaffolds were investigated by SEM. PLLA/PCL scaffolds presented an ultrafine fibrous network with the addition of a “small block” structure. Smooth and regular fibrous networks were formed when ethanol was used as the exchange medium. Properties of the scaffolds, such as thermal and mechanical properties, were also studied. The results suggested that the compressive modulus declined as PCL amount increased. The incorporation of PCL effectively contributed to reduce the rigidity of PLLA. Bovine chondrocytes were seeded onto PLLA/PCL scaffold. Cells attached onto the fibrous network and their morphology was satisfactory. This polyblend fibrous scaffold will be a potential scaffold for cartilage tissue engineering. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1676–1684, 2004     

Cell-biomaterial mechanical interaction in the framework of tissue engineering: insights, computational modeling and perspectives

Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields.     

Determination of cytocompatibility and osteogenesis properties of in situ forming collagen-based scaffolds loaded with bone synthesizing drug for bone tissue engineering

Bone tissue engineering using in situ forming 3D scaffolds can be an alternative to surgically treated scaffolds. This work aimed to develop in situ forming scaffolds using poly (lactic-co-glycolic acid) and a bone synthesizing drug (risedronate) with or without the porogenic agent (collagen). Hybrid scaffolds were formed through solvent-induced phase inversion technique and were morphologically evaluated using scanning electron microscopy (SEM). The effect of scaffolds on Saos-2 cell line viability using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test besides their effect on cell growth using fluorescence microscope was assessed. Furthermore, alkaline phosphatase (ALP) activity as well as Ca²⁺ deposition on the scaffolds was evaluated. SEM images revealed the porous structure for collagen-based scaffolds. Saos-2 cell proliferation was significantly enhanced with risedronate-loaded scaffolds compared to those lacking the drug. Porous collagen-based scaffolds were more favorable for both the cell growth and the promotion of ALP activity. Furthermore, collagen-based scaffolds promoted the Ca²⁺ deposition compared to their counterparts without collagen. Such results suggest that collagen-based scaffolds offer excellent biocompatibility for bone regeneration, where this biocompatible nature of scaffold leads to the proliferation of cells that lead to the deposition of mineral on the scaffold. Such in situ forming 3D scaffolds provide a promising noninvasive approach for bone tissue engineering.     

Fabrication of tissue engineering scaffold from poly(vinylalcohol-co-ethylene)/poly(D,L-lactic-co-glycolic acid) blend: Miscibility,thermomechanical properties,and morphology

A series of poly(DL-lactide-co-glycolic acid) (PLGA) with poly(vinylalcohol-co-ethylene) (PEVAL) blends were prepared by solution casting method. The miscibility, thermal and mechanical properties have been investigated using FTIR, DSC, and DMA techniques. The miscibility of this pair of polymers throughout compositions was proved by these methods through the single T_g and the presence of interactions between the constituents. The TGA analysis revealed three degradation zones and no sensible enhancement in the thermal stability of PLGA was noted with addition of PEVAL content. The SEM analysis revealed that the draying method dramatically influence the surface morphology of copolymers and blend. The cross section micrograph of blend scaffold containing 50 wt% of PEVAL presents microcavities of diameter pores ranged between 70 and 170 µm interconnected and uniformly distributed in the polymer matrix.     

Functionalized tricalcium phosphate and poly(3-hydroxyoctanoate) derived composite scaffolds as platforms for the controlled release of diclofenac

Novel bone substitutes such as highly porous ceramic scaffolds can serve as platforms for delivering active molecules. A common problem is to control the release of the drug, therefore, it is beneficial to use a drug-functionalized polymer coating. In this study, β-tricalcium phosphate-based porous scaffolds were obtained and coated with diclofenac-functionalized biopolymer – poly(3-hydroxyoctanoate) – P(3HO). To the best of our knowledge, studies using P(3HO) as a component in ceramic-polymer based drug delivery system for bone tissue regeneration have not yet been reported. Presented materials were comprehensively investigated by various techniques such as powder X-ray diffraction, scanning electron microscopy with energy dispersive spectroscopy, hydrostatic weighing and compression tests, pH and ionic conductivity measurements, high-performance liquid chromatography and in vitro cytotoxicity studies. The obtained diclofenac-loaded composite was not only characterised by controlled and sustained drug release, but also possessed improved mechanical properties. Moreover, the precipitation of apatite-like forms on its surface was observed after incubation in simulated body fluid, which indicates its bioactive potential. After 24 hours no cytotoxic effect on MC3T3-E1 mouse preosteoblastic cells was confirmed using indirect cytotoxicity studies. Thus, this promising multifunctional composite scaffold can be a promising candidate as an anti-inflammatory drug-delivery system in bone tissue engineering.     

A new approach for the preparation of hydrophilic poly(L‐lactide) porous scaffold for tissue engineering by using lamellar single crystals

The aim of the present work was to study the possibility of building a porous scaffold for tissue engineering with a new bottom‐up approach, obtained by assembling two‐dimensional‐micro, one‐dimensional‐nano sized poly(L ‐lactide) lamellar single crystals. This choice was dictated by the fact that polymer single crystals have structural and morphological features which can be exploited for chemical surface modifications to give a system characterized by a high specific active surface area. Indeed, the outermost amorphous regions can undergo functionalization reactions easily, whereas the inner, relatively inaccessible and inert crystalline core ensures morphological and mechanical stability. The assembling method employed to give the porous structures is based on a mould pressing, salt leaching technique and was found to be facile and versatile. In the first part of this paper we report the experimental results obtained to find the best conditions to achieve a suitable frame in terms of morphology, porosity and mechanical properties. In the second part of the paper, we describe the biological tests performed by using mouse fibroblasts seeded onto scaffolds prepared from pristine and surface hydrolysed lamellae. The results show that the samples obtained are suitable for sustaining cells which can proliferate and reach the inner pores of the scaffold containing hydrolysed single crystals much better than those prepared from pristine lamellae. Copyright © 2012 Society of Chemical Industry     

Synthesis of silicate glass/poly(l-lactide) composite scaffolds by freeze-extraction technique: Characterization and in vitro bioactivity evaluation

The main objectives of the present study were to fabricate the silicate glass/poly(l-lactide) composite scaffolds for bone engineering applications, by using the freeze-extraction technique, and to evaluate the possibility for optimizing their degradation rate by changing their glass content. The scaffolds characterized by SEM-EDXA, FT-IR, TGA and XRD. Examination of the SEM microphotographs revealed that the pore size of the scaffolds decreased as the glass content increased. The neat polymer scaffold (PLA) had a highly interconnected porous structure with a maximum pore size of 200 μm. For the composite scaffold containing glass content up to 25 wt% (SP25) and up to 50 wt% (SP50), the maximum pore size was 40 μm and 20 μm respectively. The apparent porosity was 56.56%, 52.49% and 48.74% for PLA, SP25 and SP50, respectively. The results of the degradation study showed that the water absorption of the scaffolds decreased by increasing their glass content, It reached finally to 48.71%and 30.93% for SP25 and SP50, respectively. It revealed that also the weight loss of the scaffolds increased by increasing the glass content. The final weight loss was around 5.44%, 9.31% and 26.17% for the PLA, SP25 and SP50, respectively, indicating that it was possible to modulate the degradation rate of the scaffolds by varying their glass content. In addition, the pH measurement of incubation medium indicated that the glass could compensate the acidic degradation products of the polymer. In vitro bioactivity evaluation showed that the composite scaffolds were able to induce the formation of hydroxyapaptite layer on their surfaces, demonstrating their potential application in bone engineering.     

Composite scaffolds for cartilage tissue engineering based on natural polymers of bacterial origin,thermoplastic poly(3‐hydroxybutyrate) and micro‐fibrillated bacterial cellulose

Cartilage tissue engineering is an emerging therapeutic strategy that aims to regenerate damaged cartilage caused by disease, trauma, ageing or developmental disorder. Since cartilage lacks regenerative capabilities, it is essential to develop approaches that deliver the appropriate cells, biomaterials and signalling factors to the defect site. Materials and fabrication technologies are therefore critically important for cartilage tissue engineering in designing temporary, artificial extracellular matrices (scaffolds), which support 3D cartilage formation. Hence, this work aimed to investigate the use of poly(3‐hydroxybutyrate)/microfibrillated bacterial cellulose (P(3HB)/MFC) composites as 3D‐scaffolds for potential application in cartilage tissue engineering. The compression moulding/particulate leaching technique employed in the study resulted in good dispersion and a strong adhesion between the MFC and the P(3HB) matrix. Furthermore, the composite scaffold produced displayed better mechanical properties than the neat P(3HB) scaffold. On addition of 10, 20, 30 and 40 wt% MFC to the P(3HB) matrix, the compressive modulus was found to have increased by 35%, 37%, 64% and 124%, while the compression yield strength increased by 95%, 97%, 98% and 102% respectively with respect to neat P(3HB). Both cell attachment and proliferation were found to be optimal on the polymer‐based 3D composite scaffolds produced, indicating a non‐toxic and highly compatible surface for the adhesion and proliferation of mouse chondrogenic ATDC5 cells. The large pores sizes (60 ‐ 83 µm) in the 3D scaffold allowed infiltration and migration of ATDC5 cells deep into the porous network of the scaffold material. Overall this work confirmed the potential of P(3HB)/MFC composites as novel materials in cartilage tissue engineering. © 2016 Society of Chemical Industry