Journal of Biomedical Materials Research - Part B Applied Biomaterials

Titanium and titanium alloys are key biomedical materials because of their good biocompatibility and mechanical properties. Nevertheless, infection on and around titanium implants still remains a problem which is usually difficult to treat and may lead to eventual implant removal. As a result, preventive measures are necessary to mitigate implant‐frelated infection. One important strategy is to render the implant surface antibacterial by impeding the formation of a biofilm. A number of approaches have been proposed for this purpose and they are reviewed in this article. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009

This article reports a new process chain for custom‐made three‐dimensional (3D) porous ceramic scaffolds for bone replacement with fully interconnected channel network for the repair of osseous defects from trauma or disease. Rapid prototyping and especially 3D printing is well suited to generate complex‐shaped porous ceramic matrices directly from powder materials. Anatomical information obtained from a patient can be used to design the implant for a target defect. In the 3D printing technique, a box filled with ceramic powder is printed with a polymer‐based binder solution layer by layer. Powder is bonded in wetted regions. Unglued powder can be removed and a ceramic green body remains. We use a modified hydroxyapatite (HA) powder for the fabrication of 3D printed scaffolds due to the safety of HA as biocompatible implantable material and efficacy for bone regeneration. The printed ceramic green bodies are consolidated at a temperature of 1250°C in a high temperature furnace in ambient air. The polymeric binder is pyrolysed during sintering. The resulting scaffolds can be used in tissue engineering of bone implants using patient‐derived cells that are seeded onto the scaffolds.This article describes the process chain, beginning from data preparation to 3D printing tests and finally sintering of the scaffold. Prototypes were successfully manufactured and characterized. It was demonstrated that it is possible to manufacture parts with inner channels with a dimension down to 450 μm and wall structures with a thickness down to 330 μm. The mechanical strength of dense test parts is up to 22 MPa. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005

Wound healing is a complex process that often requires treatment with antibiotics. This article reports the initial development of a biodegradable polymeric nanofiber‐based antibiotic delivery system. The functions of such a system would be (a) to serve as a biodegradable gauze, and (b) to serve as an antibiotic delivery system. The polymer used in this study was poly(lactide‐co‐glycolide) (PLAGA), and nanofibers of PLAGA were fabricated with the use of the electrospinning process. The objective of this study was to determine the effect of fabrication parameters: orifice diameter (needle gauge), polymer solution concentration, and voltage per unit length, on the morphology and diameter of electrospun nanofibers. The needle gauges studied were 16 (1.19 mm), 18 (0.84 mm), and 20 (0.58 mm), and the range of polymer solution concentration studied was from 0.10 g/mL to 0.30 g/mL. The effect of voltage was determined by varying the voltage per unit electrospinning distance, and the range studied was from 0.375 kV/cm to 1.5 kV/cm. In addition, the mass per unit area of the electrospun nanofibers as a function of time was determined and the feasibility of antibiotic (cefazolin) loading into the nanofibers was also studied. The results indicate that the diameter of nanofibers decreased with an increase in needle gauge (decrease in orifice diameter), and increased with an increase in the concentration of the polymer solution. The voltage study demonstrated that the average diameter of the nanofibers decreased with an increase in voltage. However, the effect of voltage on fiber diameter was less pronounced as compared to polymer solution concentration. The results of the areal density study indicated that the mass per unit area of the electrospun nanofibers increased linearly with time. Feasibility of drug incorporation into the nanofibers was demonstrated with the use of cefazolin, a broad‐spectrum antibiotic. Overall, these studies demonstrated that PLAGA nanofibers can be tailored to desired diameters through modifications in processing parameters, and that antibiotics such as cefazolin can be incorporated into these nanofibers. Therefore, PLAGA nanofibers show potential as antibiotic delivery systems for the treatment of wounds. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 286–296, 2004

A bone scaffold material (nano‐HA/ collagen/PLA composite) was developed by biomimetic synthesis. It shows some features of natural bone both in main composition and hierarchical microstructure. Nano‐hydroxyapatite and collagen assembled into mineralized fibril. The three‐dimensional porous scaffold materials mimic the microstructure of cancellous bone. Cell culture and animal model tests showed that the composite material is bioactive. The osteoblasts were separated from the neonatal rat calvaria. Osteoblasts adhered, spread, and proliferated throughout the pores of the scaffold material within a week. A 15‐mm segmental defect model in the radius of the rabbit was used to evaluate the bone‐remodeling ability of the composite. Combined with 0.5 mg rhBMP‐2, the material block was implanted into the defect. The segmental defect was integrated 12 weeks after surgery, and the implanted composite was partially substituted by new bone tissue. This scaffold composite has promise for the clinical repair of large bony defects according to the principles of bone tissue engineering. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 69B: 158–165, 2004

Nanofibers and nanomaterials are potentially recent additions to materials in relation to tissue engineering (TE). TE is the regeneration of biological tissues through the use of cells, with the aid of supporting structures and biomolecules. Mimicking architecture of extracellular matrix is one of the challenges for TE. Biodegradable biopolymer nanofibers with controlled surface and internal molecular structures can be electrospun into mats with specific fiber arrangement and structural integrity for drug delivery and TE applications. The polymeric materials are widely accepted because of their ease of processability and amenability to provide a large variety of cost‐effective materials, which help to enhance the comfort and quality of life in modern biomedical and industrial society. Today, nanotechnology and nanoscience approaches to scaffold design and functionalization are beginning to expand the market for drug delivery and TE is forming the basis for highly profitable niche within the industry. This review describes recent advances for fabrication of nanofiber scaffolds and interaction of cells in TE. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2008

Hydrogels are studied extensively for many tissue engineering applications, and their mechanical properties influence both cellular and tissue compatibility. However, it is difficult to compare the mechanical properties of hydrogels between studies due to a lack of continuity between rheological protocols. This study outlines a straightforward protocol to accurately determine hydrogel equilibrium modulus and gelation time using a series of rheological tests. These protocols are applied to several hydrogel systems used within tissue engineering applications: agarose, collagen, fibrin, Matrigel™, and methylcellulose. The protocol is outlined in four steps: (1) Time sweep to determine the gelation time of the hydrogel. (2) Strain sweep to determine the linear‐viscoelastic region of the hydrogel with respect to strain. (3) Frequency sweep to determine the linear equilibrium modulus plateau of the hydrogel. (4) Time sweep with values obtained from strain and frequency sweeps to accurately report the equilibrium moduli and gelation time. Finally, the rheological characterization protocol was evaluated using a composite Matrigel™‐methylcellulose hydrogel blend whose mechanical properties were previously unknown. The protocol described herein provides a standardized approach for proper analysis of hydrogel rheological properties. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1063–1073, 2014.

Autologous Preparation Rich in Growth Factors (PRGF), a small volume of plasma enriched in platelets, is a novel therapeutic strategy for the acceleration of the wound healing of a wide range of tissues because of the continuous release of multiple growth factors, including PDGF‐AB, TGF‐β1, IGF‐I, HGF, VEGF‐A, and EGF. In this article, we have characterized the PRGF preparation and designed a randomized open‐label controlled pilot trial to evaluate the effectiveness of PRGF in the treatment of chronic cutaneous ulcers. Results showed that at 8 weeks, the mean percentage of surface healed in the PRGF group was 72.94% ± 22.25% whereas it was 21.48% ± 33.56% in the control group (p < 0.05). These results, with the limitations of a pilot study, suggest that topical application of PRGF is more effective than standard therapy in helping a chronic ulcer to heal. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2008

The stabilization of dentin collagen with biocompatible crosslinking agents may be of clinical importance to improve dentin bond strength. The present study aimed to evaluate the effect of three collagen crosslinking agents on the ultimate tensile strength (UTS) of undemineralized and demineralized dentin. Ten freshly extracted sound molars were sectioned into 0.5 × 0.5 mm² thick beams. The beams were either demineralized or kept undemineralized. Then, specimens were subdivided into four groups according to treatments—PBS solution (control), 5% glutaraldehyde (GD), 0.5% proanthocyanidin PBS solution (PA), and 0.625% genipin PBS solution (GE). Specimens were kept in their respective solutions for either 4 or 40 h. To assess UTS, specimens were subjected to tensile forces at a crosshead speed of 1 mm/min. Statistical analysis was performed using two‐way ANOVA and Fisher's PLSD test (p < 0.05). Statistically significant increases in UTS were observed for demineralized dentin after PA and GE dentin treatment, when compared with those of the control group. Dentin treated with GD showed no statistically significant differences in UTS when compared with that the control. Undemineralized dentin revealed no significant differences as compared to that of the control, regardless of the collagen crosslinkers. The application of two naturally occurring crosslinkers, i.e., PA and GE, to dentin collagen significantly improves UTS, indicating its potential value in restorative dentistry. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007

Calcium silicate ceramics have been proposed as new bone repair biomaterials, since they have proved to be bioactive, degradable, and biocompatible. β‐tricalcium phosphate ceramic is a well‐known degradable material for bone repair. This study compared the effects of CaSiO₃ (α‐, and β‐CaSiO₃) and β‐Ca₃(PO₄)₂ (β‐TCP) ceramics on the early stages of rat osteoblast‐like cell attachment, proliferation, and differentiation. Osteoblast‐like cells were cultured directly on CaSiO₃ (α‐, and β‐CaSiO₃) and β‐TCP ceramics. Attachment of a greater number of cells was observed on CaSiO₃ (α‐, and β‐CaSiO₃) ceramics compared with β‐TCP ceramics after incubation for 6 h. SEM observations showed an intimate contact between cells and the substrates, significant cells adhesion, and that the cells spread and grew on the surfaces of all the materials. In addition, the proliferation rate and alkaline phosphatase (ALP) activity of the cells on the CaSiO₃ (α‐, and β‐CaSiO₃) ceramics were improved when compared with the β‐TCP ceramics. In the presence of CaSiO₃, elevated levels of calcium and silicon in the culture medium were observed throughout the 7‐day culture period. In conclusion, the results of the present study revealed that CaSiO₃ ceramics showed greater ability to support cell attachment, proliferation, and differentiation than β‐TCP ceramic. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007