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Biomedical subjects

Colleen L Flanagan

Publications and source records attributed to Colleen L Flanagan.

5 recordsLinked to original sources

Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering.

Polycaprolactone (PCL) is a bioresorbable polymer with potential applications for bone and cartilage repair. In this work, porous PCL scaffolds were computationally designed and then fabricated via selective laser sintering (SLS), a rapid prototyping technique. The microstructure and mechanical properties of the fabricated scaffolds were assessed and compared to the designed porous architectures and computationally predicted properties. Scaffolds were then seeded with bone morphogenetic protein-7 (BMP-7) transduced fibroblasts and implanted subcutaneously to evaluate biological properties and to demonstrate tissue in-growth. The work done illustrates the ability to design and fabricate PCL scaffolds with porous architecture that have sufficient mechanical properties for bone tissue engineering applications using SLS. Compressive modulus and yield strength values ranged from 52 to 67 MPa and 2.0 to 3.2 Mpa, respectively, lying within the lower range of properties reported for human trabecular bone. Finite element analysis (FEA) results showed that mechanical properties of scaffold designs and of fabricated scaffolds can be computationally predicted. Histological evaluation and micro-computed tomography (microCT) analysis of implanted scaffolds showed that bone can be generated in vivo. Finally, to demonstrate the clinical application of this technology, we designed and fabricated a prototype mandibular condyle scaffold based on an actual pig condyle. The integration of scaffold computational design and free-form fabrication techniques presented here could prove highly useful for the construction of scaffolds that have anatomy specific exterior architecture derived from patient CT or MRI data and an interior porous architecture derived from computational design optimization.

Animals↗

Regenerative versus reparative healing in tendon: a study of biomechanical and histological properties in fetal sheep.

Previous studies have shown fetal tissues heal in a regenerative fashion without scar formation. The objective of this study is to compare the healing properties of adult and fetal tendons. Time-mated pregnant ewes at 80-85 days of gestation were utilized. A partial, midsubstance tenotomy was performed in the lateral extensor fetal tendons, and analogous tenotomies were created in the maternal limbs. One week after injury, the fetal and adult animals were sacrificed, and tendons were histologically and mechanically evaluated. Immunohistochemical staining for transforming growth factor beta isoform 1 (TGF-beta1) was performed. Histologically, a gap with granulation tissue and inflammatory cells was visible in the site of wounding in the adult tendons. In the fetal tendons, no abnormalities were noted in the wound, with reconstitution of collagen architecture. TGF-beta1 expression was low in fetal but upregulated in the adult wounds. No significant differences were found in the biomechanical properties between groups. We identified regenerative healing properties in injured fetal tendon, while adult tendon tissue healed reparatively with scar formation. Fetal tendons demonstrated a limited recovery of mechanical properties after injury that was no better than that of the adult tendons at seven days. A better understanding of the mechanisms of fetal healing may lead to novel therapeutic strategies in the clinical setting.

Aging↗

Rotator cuff tendinosis in an animal model: role of extrinsic and overuse factors.

The rat shoulder animal model has been used previously to study the role of intrinsic injury (modeled as an acute insult to the tendon), extrinsic injury (modeled as external subacromial impingement), and overuse factors on rotator cuff tendinosis. These studies demonstrated that it is possible to produce rotator cuff tendinosis with any one of these factors in isolation. The current study uses the rat shoulder model to study the roles of extrinsic compression, overuse, and overuse in combination with extrinsic compression, on the development of rotator cuff tendinosis. The results of this study demonstrate that the injury created by overuse plus extrinsic compression is greater than the injuries created by overuse or extrinsic compression alone, particularly when important biomechanical variables are considered. While ineffective in causing a change in supraspinatus tendon properties in animals with normal cage activity, extrinsic compression had a significant and dramatic effect when it was combined with overuse activity. Without an additional factor, such as overhead activity, the extrinsic compression alone may be insufficient to cause tendinosis. The results of the present study support the role of multiple factors in the etiology of some rotator cuff injuries.

Animals↗

The effect of fibrin clot on healing rat supraspinatus tendon defects.

The possibility that fibrin clot, with its chemotactic and mitogenic factors, might improve the healing of a defect in the rat supraspinatus tendon was evaluated. Bilateral defects were surgically created in the rat supraspinatus tendon near the humeral insertion. One defect in each rat was filled with fibrin clot from a donor animal while the other side acted as a control. The tendons were evaluated at 3, 6, and 12 weeks. On histologic evaluation persistent defects were seen at all time points, whereas the healing tissue became less cellular with better collagen organization over time. Fibrin clot remained in the healing defects of treated shoulders at early time points. Biomechanically, there was improvement of properties over time, but they did not approach those of normal tendon by 12 weeks. There was no effect from addition of the fibrin clot except at 3 weeks, where it led to a decrease in material properties.

Animals↗