Hydroxyapatite (HA) used for bone replacement is one of the most active areas of ceramic biomaterials research currently. It has been used clinically for the last 20 years due to its excellent biocompatibility, osseoconduction and osseointegration. Many modifications have been done to develop a stronger, tougher and biocompatible ceramic biomaterial because pure HA is brittle. Researchers in Universiti Sains Malaysia had developed this value added HA that is stronger and less brittle compared to pure HA. The objective of this in vitro study was to evaluate the genotoxic characteristic of the value added HA based material by using Bacterial Reverse Mutation Assay (Ames test). The Bacterial Reverse Mutation Assay of HA was performed on Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli strain WP2 uvrA using the preincubation method in the presence and absence of an exogenous metabolic activation system. All the bacterial tester strains treated with and without S9 Mix showed no increase of revertant colonies with increase in concentration of test substance for both the dose finding test and the main test. The number of revertant colonies was less than twice that of the solvent control for all the five bacterial strains and this was reproducible for both the dose finding test and the main test. The numbers of revertant colonies in the negative and positive controls were within the background data of our laboratory. In conclusion the results of the tests showed that the value added HA was considered to have no reverse mutagenic potential under the present test conditions.
This work is aimed to develop a biocompatible, bactericidal and mechanically stable biomaterial to overcome the challenges associated with calcium phosphate bioceramics. The influence of chemical composition on synthesis temperature, bioactivity, antibacterial activity and mechanical stability of least explored calcium silicate bioceramics was studied. The current study also investigates the biomedical applications of rankinite (Ca3Si2O7) for the first time. Sol-gel combustion method was employed for their preparation using citric acid as a fuel. Differential thermal analysis indicated that the crystallization of larnite and rankinite occurred at 795 °C and 1000 °C respectively. The transformation of secondary phases into the desired product was confirmed by XRD and FT-IR. TEM micrographs showed the particle size of larnite in the range of 100-200 nm. The surface of the samples was entirely covered by the dominant apatite phase within one week of immersion. Moreover, the compressive strength of larnite and rankinite was found to be 143 MPa and 233 MPa even after 28 days of soaking in SBF. Both samples prevented the growth of clinical pathogens at a concentration of 2 mg/mL. Larnite and rankinite supported the adhesion, proliferation and osteogenic differentiation of hBMSCs. The variation in chemical composition was found to influence the properties of larnite and rankinite. The results observed in this work signify that these materials not only exhibit faster biomineralization ability, excellent cytocompatibility but also enhanced mechanical stability and antibacterial properties.
In the current practice, the clinical use of conventional skin substitutes such as autogenous skin grafts have shown several problems, mainly with respect to limited sources and donor site morbidity. In order to overcome these limitations, the use of smart synthetic biomaterials is tremendously diffusing as skin substitutes. Indeed, engineered skin grafts or analogues frequently play an important role in the treatment of chronic skin wounds, by supporting the regeneration of newly formed tissue, and at the same time preventing infections during the long-term treatment. In this context, natural proteins such as collagen-natively present in the skin tissue-embedded in synthetic polymers (i.e., PCL) allow the development of micro-structured matrices able to mimic the functions and to structure of the surrounding extracellular matrix. Moreover, the encapsulation of drugs, such as gentamicin sulfate, also improves the bioactivity of nanofibers, due to the efficient loading and a controlled drug release towards the site of interest. Herein, we have done a preliminary investigation on the capability of gentamicin sulfate, loaded into collagen-added nanofibers, for the controlled release in local infection treatments. Experimental studies have demonstrated that collagen added fibers can be efficaciously used to administrate gentamicin for 72 h without any toxic in vitro response, thus emerging as a valid candidate for the therapeutic treatment of infected wounds.
Chitosan, collagen, gelatin, polylactic acid and polyhydroxyalkanoates are notable examples of biopolymers, which are essentially bio-derived polymers produced by living cells. With the right techniques, these biological macromolecules can be exploited for nanotechnological advents, including for the fabrication of nanocarriers. In the world of nanotechnology, it is highly essential (and optimal) for nanocarriers to be biocompatible, biodegradable and non-toxic for safe in vivo applications, including for drug delivery, cancer immunotherapy, tissue engineering, gene delivery, photodynamic therapy and many more. The recent advancements in understanding nanotechnology and the physicochemical properties of biopolymers allows us to modify biological macromolecules and use them in a multitude of fields, most notably for clinical and therapeutic applications. By utilizing chitosan, collagen, gelatin, polylactic acid, polyhydroxyalkanoates and various other biopolymers as synthesis ingredients, the 'optimal' properties of a nanocarrier can easily be attained. With emphasis on the aforementioned biological macromolecules, this review presents the various biopolymers utilized for nanocarrier synthesis along with their specific synthetization methods. We further discussed on the characterization techniques and related applications for the synthesized nanocarriers.
Blood compatibility of metallocene polyethylene (mPE) was investigated after modifying the surface using hydrochloric acid. Contact angle of the mPE exposed to HCl poses a decrease in its value which indicates increasing wettability and better blood compatibility. Surface of mPE analyzed by using FTIR revealed no significant changes in its functional groups after treatment. Furthermore, scanning electron microscope images supported the increasing wettability through the modifications like pit formations and etching on the acid rendered surface. To evaluate the effect of acid treatment on the coagulation cascade, prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. Both PT and APTT were delayed significantly (P < 0.05) after 60 min exposure implying improved blood compatibility of the surfaces. Hemolysis assay of the treated surface showed a remarkable decrease in the percentage of lysis of red blood cells when compared with untreated surface. Moreover, platelet adhesion assay demonstrated that HCl exposed surfaces deter the attachment of platelets and thereby reduce the chances of activation of blood coagulation cascade. These results confirmed the enhanced blood compatibility of mPE after HCl exposure which can be utilized for cardiovascular implants like artificial vascular prostheses, implants, and various blood contacting devices.
Biocompatible metals have been revolutionizing the biomedical field, predominantly in human implant applications, where these metals widely used as a substitute to or as function restoration of degenerated tissues or organs. Powder metallurgy techniques, in specific the metal injection moulding (MIM) process, have been employed for the fabrication of controlled porous structures used for dental and orthopaedic surgical implants. The porous metal implant allows bony tissue ingrowth on the implant surface, thereby enhancing fixation and recovery. This paper elaborates a systematic classification of various biocompatible metals from the aspect of MIM process as used in medical industries. In this study, three biocompatible metals are reviewed-stainless steels, cobalt alloys, and titanium alloys. The applications of MIM technology in biomedicine focusing primarily on the MIM process setting parameters discussed thoroughly. This paper should be of value to investigators who are interested in state of the art of metal powder metallurgy, particularly the MIM technology for biocompatible metal implant design and development.
Intranasal administration is poised as a competent method in delivering drugs to the brain, because the nasal route has a direct link with the central nervous system bypassing the formidable blood-brain barrier. C17-monoglycerol ester (MGE) and glyceryl monooleate (GMO) as liquid crystal (LC)-forming lipids possess desirable formulation characteristics as drug carriers for intranasally administered drugs. This study investigated the effect of LC formulations on the pharmacokinetics of tranilast (TL), a lipophilic model drug, and its distribution in the therapeutic target regions of the brain in rats. The anatomical biodistribution of LC formulations was monitored using micro-computed tomography tandem in vivo imaging systems. MGE and GMO effectively formed LC with suitable particle size, zeta potential, and viscosity supporting the delivery of TL to the brain. MGE and GMO LC formulations enhanced brain uptake by 10- to 12-fold and 2- to 2.4- fold, respectively, compared with TL solution. The olfactory bulb had the highest TL concentration and fluorescent signals among all the brain regions, indicating a direct nose-to-brain delivery pathway of LC formulations. LC-forming lipids, MGE and GMO, are potential biomaterials in formulations intended for intranasal administration.
Among the various biomaterials available for tissue engineering and therapeutic applications, microbial polyhydroxyalkanoates (PHAs) offer the most diverse range of thermal and mechanical properties. Of particular interest are the PHAs that contain 4-hydroxybutyrate such as poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB) and poly(4-hydroxybutyrate) [P(4HB)]. These polyesters can only be synthesized by a few types of bacteria, among which Comamonas acidovorans has the most efficient metabolic pathways to channel 4HB monomers. The resulting polyesters are bioabsorbable and are being developed as a new biomaterial for medical applications. By controlling the molar ratio of the monomers, it is possible to produce materials that are as tough and elastic as rubber.
Polyhydroxyalkanoates (PHAs) are biodegradable polyesters produced by microorganisms, under unbalanced growth conditions, as a carbon storage compound. PHAs are composed of various monomers such as 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate (3HHx). Silk fibroin (SF) derived from Bombyx mori cocoons, is a widely studied protein polymer commonly used for biomaterial applications. In this study, non-woven electrospun films comprising a copolymer of 3HB and 3HHx [P(3HB-co-3HHx)], SF and their blends were prepared by electrospinning technique. The growth and osteogenic differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were studied using different types of fabricated electrospun films. The differentiation study revealed that electrospun P(3HB-co-3HHx)/SF film supports the differentiation of hUC-MSCs into the osteogenic lineage, confirmed by histological analysis using Alizarin Red staining, energy dispersive X-ray (EDX) and quantitative real-time PCR analysis (qPCR). Electrospun P(3HB-co-3HHx)/SF film up-regulated the expression of osteogenic marker genes, alkaline phosphatase (ALP) and osteocalcin (OCN), by 1.6-fold and 2.8-fold respectively, after 21 days of osteogenic induction. In conclusion, proliferation and osteogenic differentiation of hUC-MSCs were enhanced through the blending of P(3HB-co-3HHx) and SF. The results from this study suggest that electrospun P(3HB-co-3HHx)/SF film is a promising biomaterial for bone tissue engineering.
Aloe vera (AV) and tetracycline hydrochloride (TCH) exhibit significant properties such as anti-inflammatory, antioxidant and anti-bacterial activities to facilitate skin tissue engineering. The present study aims to develop poly-ε-caprolactone (PCL)/ AV containing curcumin (CUR), and TCH loaded hybrid nanofibrous scaffolds to validate the synergistic effect on the fibroblast proliferation and antimicrobial activity against Gram-positive and Gram-negative bacteria for wound healing. PCL/AV, PCL/CUR, PCL/AV/CUR and PCL/AV/TCH hybrid nanofibrous mats were fabricated using an electrospinning technique and were characterized for surface morphology, the successful incorporation of active compounds, hydrophilicity and the mechanical property of nanofibers. SEM revealed that there was a decrease in the fiber diameter (ranging from 360 to 770 nm) upon the addition of AV, CUR and TCH in PCL nanofibers, which were randomly oriented with bead free morphology. FTIR spectra of various electrospun samples confirmed the successful incorporation of AV, CUR and TCH into the PCL nanofibers. The fabricated nanofibrous scaffolds possessed mechanical properties within the range of human skin. The biocompatibility of electrospun nanofibrous scaffolds were evaluated on primary human dermal fibroblasts (hDF) by MTS assay, CMFDA, Sirius red and F-actin stainings. The results showed that the fabricated PCL/AV/CUR and PCL/AV/TCH nanofibrous scaffolds were non-toxic and had the potential for wound healing applications. The disc diffusion assay confirmed that the electrospun nanofibrous scaffolds possessed antibacterial activity and provided an effective wound dressing for skin tissue engineering.
Many wounds are unresponsive to currently available treatment techniques and therefore there is an immense need to explore suitable materials, including biomaterials, which could be considered as the crucial factor to accelerate the healing cascade. In this study, we fabricated polyhydroxyalkanoate-based antibacterial mats via an electrospinning technique. One-pot green synthesized graphene-decorated silver nanoparticles (GAg) were incorporated into the fibres of poly-3 hydroxybutarate-co-12 mol.% hydroxyhexanoate (P3HB-co-12 mol.% HHx), a co-polymer of the polyhydroxyalkanoate (PHA) family which is highly biocompatible, biodegradable, and flexible in nature. The synthesized PHA/GAg biomaterial has been characterized by field emission scanning electron microscopy (FESEM), elemental mapping, thermogravimetric analysis (TGA), UV-visible spectroscopy (UV-vis), and Fourier transform infrared spectroscopy (FTIR). An in vitro antibacterial analysis was performed to investigate the efficacy of PHA/GAg against gram-positive Staphylococcus aureus (S. aureus) strain 12,600 ATCC and gram-negative Escherichia coli (E. coli) strain 8739 ATCC. The results indicated that the PHA/GAg demonstrated significant reduction of S. aureus and E. coli as compared to bare PHA or PHA- reduced graphene oxide (rGO) in 2 h of time. The p value (p < 0.05) was obtained by using a two-sample t-test distribution.
Selections of collagen available commercially were tested for their biocompatibility as scaffold to promote cell growth in vitro via simple collagen fast test and cultivation of mammalian cells on the selected type of collagen. It was found that collagen type C9791 promotes the highest degree of aggregation as well as cells growth. This preliminary study also indicated potential use of collagen as scaffold in engineered tissue.
Since ancient Egypt, orthosis was generally made from wood and then later replaced with metal and leather which are either heavy, bulky, or thick decreasing comfort among the wearers. After the age of revolution, the manufacturing of products using plastics and carbon composites started to spread due to its low cost and form-fitting feature whereas carbon composite were due to its high strength/stiffness to weight ratio. Both plastic and carbon composite has been widely applied into medical devices such as the orthosis and prosthesis. However, carbon composite is also quite expensive, making it the less likely material to be used as an Ankle-Foot Orthosis (AFO) material whereas plastics has low strength. Kenaf composite has a high potential in replacing all the current materials due to its flexibility in controlling the strength to weight ratio properties, cost-effectiveness, abundance of raw materials, and biocompatibility. The aim of this review paper is to discuss on the possibility of using kenaf composite as an alternative material to fabricate orthotics and prosthetics. The discussion will be on the development of orthosis since ancient Egypt until current era, the existing AFO materials, the problems caused by these materials, and the possibility of using a Kenaf fiber composite as a replacement of the current materials. The results show that Kenaf composite has the potential to be used for fabricating an AFO due to its tensile strength which is almost similar to polypropylene's (PP) tensile strength, and the cheap raw material compared to other type of materials.
Global issues such as environmental problems and food security are currently of concern to all of us. Circular bioeconomy is a promising approach towards resolving these global issues. The production of bioenergy and biomaterials can sustain the energy-environment nexus as well as substitute the devoid of petroleum as the production feedstock, thereby contributing to a cleaner and low carbon environment. In addition, assimilation of waste into bioprocesses for the production of useful products and metabolites lead towards a sustainable circular bioeconomy. This review aims to highlight the waste biorefinery as a sustainable bio-based circular economy, and, therefore, promoting a greener environment. Several case studies on the bioprocesses utilising waste for biopolymers and bio-lipids production as well as bioprocesses incorporated with wastewater treatment are well discussed. The strategy of waste biorefinery integrated with circular bioeconomy in the perspectives of unravelling the global issues can help to tackle carbon management and greenhouse gas emissions. A waste biorefinery-circular bioeconomy strategy represents a low carbon economy by reducing greenhouse gases footprint, and holds great prospects for a sustainable and greener world.
Use of synthetic hydroxyapatite (HA) in biomedical applications is well warranted. It has shown to have an excellent biocompatibility in human tooth and bones. Additionally it has been documented to possess antibacterial potentials. The present study was conducted to assess the presence of any such potential in locally produced (HA) using Streptococcus mutans, a common pathogen in the oral cavity. The study was carried out using 50, 100, 150, 200, 300, 400 and 800 mg/ml concentration of HA. The antibacterial property of HA was assessed using Miles and Misra method. Our studies showed that bacterial growth inhibitions of S. mutans occurred from 50 mg/ml, and complete inhibition was perceived at concentrations at 200mg/ml of HA. The antibacterial property HA should be used to good advantage as a bioactive biomaterial in dental and maxillofacial applications.
The paper presents a method of producing synthetic Hydroxyapatite (HA) Ca10(PO4)6(OH)2 and other apatites for biological use by solid-state reaction. The solid-state reaction involves mix-grinding dry powders of beta-tricalcium phosphate powder (TCP) and either calcium hydroxide (Ca(OH)2) or calcium carbonate (CaCO3) or combination thereof, from pure commercial chemicals or derived from natural limestone or from seashells, of total calcium/phosphorus molar ratio between 1.5 to 2.0, to particle size of less than 10 microns, and firing the resultant powder to temperature between 600 degrees C - 1250 degrees C in atmosphere or in controlled atmospheric condition. The resultant apatites formed were characterised using XRD, SEM-EDX and FTIR. The presented reaction process was found to be much simpler compared to conventional methods of producing synthetic apatites since it involves only dry mix-grinding of the reactants before firing at high temperatures based on the required levels of purity. It can also produce synthetic apatites with good reproducibility in a shorter time. Thus the presented method has a great industrial value.
Titanium and its alloy are known as important load-bearing biomaterials. The major drawbacks of these metals are fibrous formation and low corrosion rate after implantation. The surface modification of biomedical implants through various methods such as plasma spray improves their osseointegration and clinical lifetime. Different materials have been already used as coatings on biomedical implant, including calcium phosphates and bioglass. However, these materials have been reported to have limited clinical success. The excellent bioactivity of calcium silicate (Ca-Si) has been also regarded as coating material. However, their high degradation rate and low mechanical strength limit their further coating application. Trace element modification of (Ca-Si) bioceramics is a promising method, which improves their mechanical strength and chemical stability. In this review, the potential of trace element-modified silicate coatings on better bone formation of titanium implant is investigated.
Recent progress on highly tough and stretchable polymer networks has highlighted the potential of wearable electronic devices and structural biomaterials such as cartilage. For some given applications, a combination of desirable mechanical properties including stiffness, strength, toughness, damping, fatigue resistance, and self-healing ability is required. However, integrating such a rigorous set of requirements imposes substantial complexity and difficulty in the design and fabrication of these polymer networks, and has rarely been realized. Here, we describe the construction of supramolecular polymer networks through an in situ copolymerization of acrylamide and functional monomers, which are dynamically complexed with the host molecule cucurbituril (CB). High molecular weight, thus sufficient chain entanglement, combined with a small-amount dynamic CB-mediated non-covalent crosslinking (2.5 mol%), yields extremely stretchable and tough supramolecular polymer networks, exhibiting remarkable self-healing capability at room temperature. These supramolecular polymer networks can be stretched more than 100× their original length and are able to lift objects 2000× their weight. The reversible association/dissociation of the host-guest complexes bestows the networks with remarkable energy dissipation capability, but also facile complete self-healing at room temperature. In addition to their outstanding mechanical properties, the networks are ionically conductive and transparent. The CB-based supramolecular networks are synthetically accessible in large scale and exhibit outstanding mechanical properties. They could readily lead to the promising use as wearable and self-healable electronic devices, sensors and structural biomaterials.
Dentistry has searched for an ideal material to place in osseous defects for many years. Endogenous bone replacement has been the golden standard but involves additional surgery and may be available in limited quantities. Also, the exogenous bone replacement poses a risk of viral or bacterial transmission and the human body may even reject them. Therefore, before new biomaterials are approved for medical use, mutagenesis systems to exclude cytotoxic, mutagenic or carcinogenic properties are applied worldwide. The present preliminary study was carried out in five male New Zealand white rabbits (Oryctolagus cuniculus). Porous form of synthetic hydroxyapatite granules (500 mg), manufactured by School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, Penang, was implanted in the femur of the rabbits. Blood samples were collected prior to implantation and one week after implantation. The blood was cultured in vitro and the cell division was arrested at metaphase using colcemid. This was followed by the hypotonic treatment and fixation. Then, the chromosomes were prepared and stained for analysis. The modal chromosome number of rabbit (Oryctolagus cuniculus) was found to be 2n=44. The mean mitotic index values prior to and after implantation were 3.30 ± 0.66 and 3.24 ± 0.27 per cent respectively. No gross chromosome aberrations, both numerical and structural were noticed either prior to or after implantation of the biomaterial. These findings indicate that the test substance, synthetic hydroxyapatite granules does not produce gross chromosome aberrations under the present test conditions in rabbits.