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Influence of Scaffold Architecture on the Induction of Organized Tissue Ingrowth, 01-9379

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Principal Investigators
(Joe McDonough)
Neal K. Vail
David Carnes (UTHSC-SA)

Inclusive Dates: 03/01/03 - 06/30/03

Background - Each year in the United States, approximately 600,000 patients undergo bone-grafting procedures to affect defect repair as a result of trauma, disease, congential disorders, and aging. Bone grafts can be autologous, allograft, or artificial. Autologous bone grafts are harvested directly from the patient and are the "gold standard," since they are inherently biocompatible, osteoconductive, osteoinductive, and ostegenic. Allografts, derived from donor tissues, are osteoconductive, but their osteoinductive properties are questionable due to required sterilization. Artificial grafts are either synthetic or derived from other natural sources (e.g. bovine and coral). These artificial grafts are osteoconductive, but osteoinductive and osteogenic properties must be achieved using specific growth factors. Current graft research is primarily directed toward the development of synthetic scaffolds because of serious drawbacks with auto- and allo-grafts, such as second site morbidity in the case of autologous grafts and the risk of disease tranmission associated with allografts.

Literature supports the hypothesis that neovascularization and angiogensis, as well as a suitable matrix scaffold are essential factors for bone formation. The essential relationship between bone formation and angiogenesis has been shown both for endochondral bone formation and fracture repair. Thus, development of a scaffold architecture that supports vascular cell ingrowth is an essential component of bioengineering efforts to provide synthetic materials that promote bone wound healing.

In spite of the considerable research, the appropriate relationship of scaffold architecture to neovascularization and osteogenesis remains ambiguous. This is particularly true with respect to optimum pore size and interconnectivity because there are no studies in the literature that systematically investigate these characteristics under controlled conditions. Literature suggests there is a certain size of pore geometry that supports osteoblastic activities related to vascularization, and that pore dimension and inteconectivity are key factors in structural design that ensure tissue attachment and osteoid formation.

Approach - The goal is to develop new scaffold technology for augmentation and repair of skeletal defects. The hypothesis is that scaffolds having an engineered porous structure are required to promote neovascularization and subsequent complete infiltration of new bone growth. The scope of this quick-look is to establish preliminary data in support of the hypothesis necessary to seek external funding mechanisms. Specifically, we will study the influence of specific macroporous geometries on vascular cell ingrowth in vitro under controlled conditions. The project was divided into two tasks. The first task focused on the preparation of scaffolds with controlled pore structures. The second task focused on the in vitro testing of the scaffolds to examine microvessel ingrowth.

Accomplishments - Scaffolds were prepared using a casting method followed by high temperature sintering. Nanosized HAp powders were formulated into slurries for casting operations. A mold was designed to prepare constructs approximately 10x10x2 mm3 in dimension. The mold was designed so polymer fibers could be oriented in the mid-plane of the constructs (i.e., at 1 mm) to introduce controlled pore structures (Figure 1). Polypropylene fibers of various diameters were used to generate the pore structures. These fibers were analyzed for melt point (Tm = 168°C) and thermal decomposition (decomposition onset at ~400°C and complete by 525°C) by differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA), respectively. Castings were prepared, and all samples were fired by heating the samples at 5°C/min to 500°C and holding for 1 hour, then heating at 2°C/min to 1300°C and holding for 2 hours, followed by cooling to ambient temperature at 5C/min.

Experiments are in progress to examine microvessel ingrowth into the macropores of the various scaffolds. Microvessel ingrowth is being evaluated using histological analysis.

Figure 1. Scaffold macropore geometry located at the mid-plane. The macropores have lengths that are multiples of the scaffold dimension and each pore has equivalent diameters. The minimum spacing between pores is about 500 m.
Figure 2. A cast scaffold containing 255 m diameter fibers for pore generation.
Figure 3. A fired scaffold with resulting pores approximately 200 (m in diameter.)

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