A biomimetic multi-layered collagen-based scaffold for osteochondral repair.

Cartilage and osteochondral defects pose a significant challenge in orthopedics. Tissue engineering has shown promise as a potential method for the treatment of such defects; however, a long-lasting repair strategy has yet to be realized. This study focuses on the development of a layered construct for osteochondral repair, fabricated through a novel \u22iterative layering\u22 freeze-drying technique. The process involved repeated steps of layer addition followed by freeze-drying, enabling control over material composition, pore size and substrate stiffness in each region of the construct, while also achieving a seamlessly integrated layer structure. The novel construct developed mimics the inherent gradient structure of healthy osteochondral tissue: a bone layer composed of type I collagen and hydroxyapatite (HA), an intermediate layer composed of type I collagen, type II collagen and HA and a cartilaginous region composed of type I collagen, type II collagen and hyaluronic acid. The material properties were designed to provide the biological cues required to encourage infiltration of host cells from the bone marrow while the biomechanical properties were designed to provide an environment optimized to promote differentiation of these cells towards the required lineage in each region. This novel osteochondral graft was shown to have a seamlessly integrated layer structure, high levels of porosity (\u3e97%), a homogeneous pore structure and a high degree of pore interconnectivity. Moreover, homogeneous cellular distribution throughout the entire construct was evident following in vitro culture, demonstrating the potential of this multi-layered scaffold as an advanced strategy for osteochondral defect repair

Contraceptive use in women enrolled into preventive HIV vaccine trials: experience from a phase I/II trial in East Africa.

HIV vaccine trials generally require that pregnant women are excluded from participation, and contraceptive methods must be used to prevent pregnancy during the trial. However, access to quality services and misconceptions associated with contraceptive methods may impact on their effective use in developing countries. We describe the pattern of contraceptive use in a multi-site phase I/IIa HIV Vaccine trial in East Africa (Uganda, Kenya and Tanzania) and factors that may have influenced their use during the trial.Pregnancy prevention counseling was provided to female participants during informed consent process and at each study visit. Participants' methods of contraception used were documented. Methods of contraceptives were provided on site. Pregnancy testing was done at designated visits during the trial. Obstacles to contraceptive use were identified and addressed at each visit.Overall, 103 (31.8%) of a total of 324 enrolled volunteers were females. Female participants were generally young with a mean age of 29(+/-7.2), married (49.5%) and had less than high school education (62.1%). Hormonal contraceptives were the most common method of contraception (58.3%) followed by condom use (22.3%). The distribution of methods of contraception among the three sites was similar except for more condom use and less abstinence in Uganda. The majority of women (85.4%) reported to contraceptive use prior to screening. The reasons for not using contraception included access to quality services, insufficient knowledge of certain methods, and misconceptions.Although hormonal contraceptives were frequently used by females participating in the vaccine trial, misconceptions and their incorrect use might have led to inconsistent use resulting in undesired pregnancies. The study underscores the need for an integrated approach to pregnancy prevention counseling during HIV vaccine trials.ClinicalTrials.gov NCT00123968

Duration of Contraceptive use prior to Screening, Contraceptive Methods Used at enrollment and Pregnancies Reported

<p>Duration of Contraceptive use prior to Screening, Contraceptive Methods Used at enrollment and Pregnancies Reported</p

Demographic Characteristics of Female Study Participants by Site

<p>Demographic Characteristics of Female Study Participants by Site</p

Use of Hormonal Contraceptives by Participant Characteristics^*

*<p>Response variable coded as: 0 = Did not use hormonal contraceptives, 1 = Used hormonal contraceptives.</p>**<p>Significant observation.</p

Pattern of Contraceptive Use at Enrolment by Selected Demographic Factors (All Sites)

<p>Pattern of Contraceptive Use at Enrolment by Selected Demographic Factors (All Sites)</p

Previous Condom Use as Contraception by Participant Characteristics^*

*<p>Response variable coded as: 0 = Did not use condom for contraception, 1 = Used condoms as contraception.</p>**<p>Significant observation.</p