Novel Strategy for Surface Modification of Titanium Implants towards the Improvement of Osseointegration Property and Antibiotic Local Delivery.

The topography and chemical composition modification of titanium (Ti) implants play a decisive role in improving biocompatibility and bioactivity, accelerating osseointegration, and, thus, determining clinical success. In spite of the development of surface modification strategies, bacterial contamination is a common cause of failure. The use of systemic antibiotic therapy does not guarantee action at the contaminated site. In this work, we proposed a surface treatment for Ti implants that aim to improve their osseointegration and reduce bacterial colonization in surgery sites due to the local release of antibiotic. The Ti discs were hydrothermally treated with 3M NaOH solution to form a nanostructured layer of titanate on the Ti surface. Metronidazole was impregnated on these nanostructured surfaces to enable its local release. The samples were coated with poly(vinyl alcohol)-PVA films with different thickness to evaluate a possible control of drug release. Gamma irradiation was used to crosslink the polymer chains to achieve hydrogel layer formation and to sterilize the samples. The samples were characterized by XRD, SEM, FTIR, contact angle measurements, "in vitro" bioactivity, and drug release analysis. The alkaline hydrothermal treatment successfully produced intertwined, web-like nanostructures on the Ti surface, providing wettability and bioactivity to the Ti samples (Ti + TTNT samples). Metronidazole was successfully loaded and released from the Ti + TTNT samples coated or not with PVA. Although the polymeric film acted as a physical barrier to drug delivery, all groups reached the minimum inhibitory concentration for anaerobic bacteria. Thus, the surface modification method presented is a potential approach to improve the osseointegration of Ti implants and to associate local drug delivery with dental implants, preventing early infections and bone failure.

Effectiveness of Epidermal Growth Factor Loaded Carboxymethylcellulose (EGF-CMC) Hydrogel in Biofilm Formation in Wounds of Diabetic Patients: A Randomized Clinical Trial.

Diabetic patients frequently develop wounds, which can be colonized by bacteria, mainly Staphylococcus aureus and Pseudomonas aeruginosa, with the ability to form biofilms. This study aimed to evaluate the colonization and biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa in chronic wounds of diabetic patients treated with a bioactive dressing (EGF-CMC), which consisted of a 2% carboxymethylcellulose (CMC) hydrogel loaded with epidermal growth factor (EGF). This randomized clinical trial was conducted with 25 participants: 14 treated with EGF-CMC hydrogel and 11 treated with CMC hydrogel for 12 weeks. Participants with type 2 diabetes mellitus were selected. All had diabetic foot ulcers or chronic venous ulcers. Swab collections were performed on weeks 1, 6, and 12. The laboratory analyses included the identification of strains, microbial quantification, virulence gene investigation, and the evaluation of biofilm formation. In total, 13 S. aureus strains and 15 P. aeruginosa strains were isolated. There were no statistically significant differences regarding bacterial loads and virulence genes. However, EGF-CMC-hydrogel-treated wounds were colonized by strains with lower biofilm formation abilities. The probability of isolating biofilm-producing strains from CMC-hydrogel-treated wounds was 83% greater than the probability of isolating biofilm-producing strains from EGF-CMC-treated wounds.

Nanostructured Electrospun Polycaprolactone-Propolis Mats Composed of Different Morphologies for Potential Use in Wound Healing.

This study aimed to investigate different types of morphologies obtained using the electrospinning process to produce a material that enables wound healing while performing a controlled release. Using benign solvents, the authors prepared and characterised electrospun polycaprolactone mats loaded with propolis, a popular extract in traditional medicine with potential for skin repair. Different morphologies were obtained from distinct storage periods of the solution before electrospinning to investigate the effect of PCL hydrolysis (average diameters of fibres and beads: 159.2-280.5 nm and 1.9-5.6 µm, respectively). Phytochemical and FTIR analyses of the extract confirmed propolis composition. GPC and viscosity analyses showed a decrease in polymer molecular weight over the storage period (about a 70% reduction over 14 days) and confirmed that it was responsible for the nanostructure diversity. Moreover, propolis acted as a lubricant agent, affecting the spun solutions' viscosity and the thermal properties and hydrophilicity of the mats. All samples were within the value range of the water vapour transpiration rate of the commercial products (1263.08 to 2179.84 g/m2·day). Even though the presence of beads did not affect the propolis release pattern, an in vitro wound-healing assay showed that propolis-loaded mats composed of beaded fibres increased the cell migration process. Thus, these films could present the potential for use in wound dressing applications.

rhEGF-Loaded Hydrogel in the Treatment of Chronic Wounds in Patients with Diabetes: Clinical Cases.

The aim of the study was to evaluate the healing process of chronic wounds treated with carboxymethylcellulose loaded with recombinant human epidermal growth factor in patients with diabetes. The case series consisted of 10 patients treated at the university hospital for 12 weeks. Data were analyzed using SPSS version 22.0. according to the intention to treat the principle, without the loss or exclusion of the participants. The sample consisted of 70% (7/10) males with a mean age of 61.9 years (±9.4); all (100%) had diabetes mellitus and 70% (7/10) had systolic hypertension associated with diabetes mellitus. Sixty percent (6/10) presented lesions of diabetic etiology and 40% (4/10) presented lesions of venous etiology; 70% (7/10) had had lesions for less than 5 years. The mean glycated hemoglobin was 7.8% (±2.7%), while the mean ankle-arm index (AAI) was 0.94 (±0.21). The mean initial area of all wounds was 13.4 cm², and the mean final area was 7.8 cm2, with a reduction rate of 28.9% over the 12 weeks of treatment. The reduction rate of diabetic ulcers was higher (33.4%) than that of venous ulcers (22.1%). Regarding the type of tissue, there was an increase in granulation and epithelialization, and a decrease in slough and the amount of exudate that were statistically significant (p = 0.021). No participant had severe or local adverse events during the study period. Epidermal growth factor was effective in the treatment of chronic wounds, especially diabetic ulcers, resulting in the reduction of the wound area and the improvement of tissue and exudate quality.

Evaluation of bone marrow stem cell response to PLA scaffolds manufactured by 3D printing and coated with polydopamine and type I collagen.

The majority of synthetic polymers used in 3 D printing are not designed to promote specific cellular interactions and hence possess limited bioactivity. Most of the strategies proposed to overcome this limitation demand multiple and expensive processing steps. This study aimed to evaluate the surface modification of 3D-printed poly(lactic acid) (PLA) scaffolds with polydopamine (PDA) coating as an alternative strategy to enhance their bioactivity and to facilitate the immobilization of type I collagen (COL I) onto the implant surface. Physical and chemical properties of PLA scaffolds coated with PDA, COL I or both were evaluated. The response of porcine bone marrow stem cells (MSCs) to the coatings was also investigated. The PDA layer improved COL immobilization onto the surface of the PLA scaffolds by 92%. The combination of PDA and COL functionalizations provided the best conditions for early-stage (<7 days) cell response. In addition, the PDA plus COL surface facilitated the robust deposition of extracellular matrix in the first 14 days of cell culture. Although the behavior of the MSCs appeared to be similar for both uncoated PLA and PDA plus COL-coated scaffolds by day 21, cells seeded onto PDA plus COL scaffolds produced substantially higher amounts of alkaline phosphatase. These results indicate that the osteoinductivity of 3D-printed PLA scaffolds can be enhanced by PDA and type I collagen coatings. This surface modification of polymeric scaffolds represents a promising strategy for bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 37-49, 2019.