Mokhamad Fakhrul Ulum

Evidences of in vivo bioactivity of Fe-bioceramic composites for temporary bone implants.

Iron-bioceramic composites have been developed as biodegradable implant materials with tailored degradation behavior and bioactive features. In the current work, in vivo bioactivity of the composites was comprehensively studied by using sheep animal model. Five groups of specimens (Fe-HA, Fe-TCP, Fe-BCP composites, and pure-Fe and SS316L as controls) were surgically implanted into medio proximal region of the radial bones. Real-time ultrasound analysis showed a decreased echo pattern at the peri-implant biodegradation site of the composites indicating minimal tissue response during the wound healing process. Peripheral whole blood biomarkers monitoring showed a normal dynamic change of blood cellular responses and no stress effect was observed. Meanwhile, the released Fe ion concentration was increasing along the implantation period. Histological analysis showed that the composites corresponded with a lower inflammatory giant cell count than that of SS316L. Analysis of the retrieved implants showed a thicker degradation layer on the composites compared with pure-Fe. It can be concluded that the iron-bioceramic composites are bioactive and induce a preferable wound healing process.

Animal Study and Pre-clinical Trials of Biomaterials

An in vivo study is one of the most important steps in the process of translating biomaterials to clinical applications. It is mostly conducted to confirm in vitro results before going further to clinical trials. Appropriate use of animal models in the in vivo studies of biomaterials and medical devices is mandatory and should meet the approved regulations and ethics as defined by both local and international regulatory bodies. These studies involve the use of various approaches and protocols in order to know the body responses both local and systemic and to find out the short- and long-term responses of the body toward the implanted biomaterials or devices. This chapter describes complete procedures and practices of in vivo studies starting from selection of appropriate animal model, pre-implantation, surgical procedure and post-implantation, and monitoring of material-host responses. Some experiences of in vivo studies done by Indonesian researchers and the development of new implants are also presented.

In vivo study of hydroxyapatite-chitosan and hydroxyapatite-tricalcium phosphate bone graft in sheep's bone as animal model

This study describes the in vivo evaluation study of bones implanted with graft of hydoxyapatite-chitosan (HA-C) and hydroxyapatite-tricalcium phosphate (HA-TCP) composite in sheeps bone as the animal model for human. This study was done in two parts, non-invasive clinical imaging study, i.e. brightness mode ultrasound (B-mode US) and conventional radiography (CR) technique, and morphological study of the bone healing process. Six sheep were used in this study and separated in two groups, three sheep for each group. The implantation surgery was done aseptically by creating a 4 mm diameter and 7 mm depth hole on each left and right hind limb of proximal medial tibial bone. First group implanted of HA-TCP at the left tibial and the second group by the HA-C composite. The right tibial of both groups served as control, which was drilled but not implanted. The CR and US were performed one day before and 7, 21, 30 days after implantation. Bones were harvested after 30, 60, and 90 days post-surgery and observed for morphological study. The B-mode US showed that inflammation and early bone remodeling occurred of both implants at subcutaneus area seven days after implantation and decreased 30 days after. Furthermore, the CR technique showed that both implant were still intact on site 90 days after, therefore, indicated minimal absorption or even not absorbed at all. The morphological evaluation showed that HA-TCP had been degradable 30 days after and continued, indicated signs for biocompatibility, biodegradability, bioresorbable, bioactivity and osteo conductivity properties. On the other hand, HA-C graft showed only biocompatibility characteristics 90 days after implantation. The result showed that the healing process of HA-TCP faster than HA-C but nevertheless, both composite still slower healing process than control bone.

Mechanical and corrosion properties of partially degradable bone screws made of pure iron and stainless steel 316L by friction welding

This paper reports a series of in vitro, ex vivo and in vivo mechanical and corrosion studies of pin and screw prototype made of friction welded pure iron and 316L type stainless steel aiming to evaluate the applicability of the partially removable bone screws. Results showed that the pin possesses bending, tensile and torsional strengths of 1706±147, 666±7 and 0.34±0.03 MPa, respectively. The pin degraded at an average weight loss rate of 17.15×10−5 g cm−2 day−1 and released Fe ions at an average concentration of 2.38 ppm. Plastic deformation induced by torsion increased the corrosion rate of the pin from 0.0014 to 0.0137 mm year−1. The maximum pull-out load of the screw prototypes was 3800 N with a calculated failure strength by shear load equal to 22.2 kN which is higher than the strength of the cortical bone. Detailed analysis of the rat’s blood cells during 60 days of the pin implantation indicated a normal response with low neutrophils/ lymphocytes ratio of 0.3‒0.5. Iron ion concentration in the rat’s blood slightly increased from 55 to 61 ppm without affecting the tissue recovering and healing phase. Histological evaluation confirmed the presence of macrophage cells as a normal response to the released iron particles around the iron section of the pin.

Assessment of prolonged tissue response to porousiron implant by radiodensity approach

Porous iron has been recently introduced as new biomaterials for bone scaffolds. As a metal that degrades in the in vivo setting (biodegradable metal), little has been known for its cell-material interaction within the living tissue especially in the view of its applications for bone implant materials. Therefore, the aim of this study is to assess tissue response to the implantation of porous iron in the in vivo setting using rats as animal model and radiographic examination. Ten adult Sprague Dawley rats received the implantation of porous iron implants having different porosity into their femoral bone followed by radiographic examination up to 5 months post-implantation. Results shows differences in the opacity of radiographic images where the implants looked more radiopaque than bone and muscle. Radiodensity values of the implants decreases overtime indicating they experienced progressive degradation. This values dynamically change over time up to 5 months in relation to the event of chronic inflammation, degradation and bone healing process.

Peripheral white blood cells profile of biodegradable metal implant in mice animal model

Biocompatibility or safety of the medical device is considered important. It can be determined by blood profile examination. The aim of this study was to assess the biocompatibility of biodegradable metal implant through peripheral white blood cells (WBCs) profile approach. Forty eight male ddy mice were divided into four groups according to the materials implanted: iron wire (Fe), magnesium rod (Mg), stainless steel surgical wire (SS316L) and control with sham (K). Implants were inserted and attached onto the right femoral bone on latero-medial region. In this study, peripheral white blood cells and leukocyte differentiation were the parameters examined. The result showed that the WBCs value of all groups were decreased at the first day after implantation, increased at the 10th day and continued increasing at the 30th day of observation, except Mg group which has decreased. Neutrophil, as an inflammatory cells, was increased at the early weeks and decreased at the day-30 after surgery in all groups. Despite, these values during the observation were still within the normal range. As a conclus ion, biodegradable metal implants lead to an inflammatory reaction, with no adverse effect on WBC value found.