Biomedical subjects

Marc Hedrick

Publications and source records attributed to Marc Hedrick.

3 recordsLinked to original sources

PubMed2004

Bacteriostatic properties of biomatrices against common orthopaedic pathogens.

Tissue-engineered grafts for tissue regeneration include either mature or progenitor cells seeded onto biomatrices that provide shape and support for developing tissue. Popular biomaterials used in orthopaedic surgery include collagen type I, hyaluronic acid, hydroxyapatite, and polylactic polyglycolic acid (PLGA). Biomatrices with bacteriostatic properties may be beneficial in promoting tissue-engineered graft survival in patients susceptible to infection. We evaluated the bacteriostatic effects of these biomaterials on the growth of the four most common orthopaedic bacterial pathogens: Staphylococcus aureus, Staphylococcus epidermidis, beta-hemolytic Streptococcus, and Pseudomonas aeruginosa. Hyaluronic acid demonstrated the largest bacteriostatic effect on these pathogens by inhibiting bacterial growth by an average of 76.8% (p = 0.0005). Hydroxyapatite and collagen inhibited growth on average by 49.7% (p = 0.011) and 37.5% (p = 0.102), respectively. PLGA exhibited the least bacteriostasis with an average inhibition of 9.8% (NS) and actually accelerated the growth of beta-hemolytic Streptococcus and P. aeruginosa.

Anti-Bacterial Agents↗

PubMed2003

Precursor tissue analogs as a tissue-engineering strategy.

Natural tissues are composed of functionally diverse cell types that are organized in spatially complex arrangements. Organogenesis of complex tissues requires a coordinated sequential transformation process, with individual stages involving time-dependent expression of cell-cell, cell-matrix, and cell-signal interactions in three dimensions. The common theme of temporal-spatial patterning of these cellular interactions is also observed in other physiological processes, such as growth and development, wound healing, and tumor migration. The "precursor tissue analog" (PTA) applies the temporal-spatial patterning theme to tissue engineering. The goal of PTA in tissue engineering is not to fabricate the final transplantable tissue but rather to guide the dynamic organization, maturation, and remodeling leading to the formation of normal and functional tissues. We describe the critical design principles of PTA. First, structural, mechanical, and physiological requirements of the PTA as a temporary scaffold must be met by a fabrication method with flexibility. The fabrication potential incorporating biological materials such as living cells and plasmid DNA has been addressed. Second, the PTA concept is considered suitable for future tissue engineering in light of the use of undifferentiated stem cells, and may possess a capability to guide stem cells toward diverse differentiation characteristics in situ. To this end, the behavior of the engineered cell and tissue must be monitored in detail. The development of a practical phenotype monitoring system such as a DNA microarray may be integral to the fabrication strategies of PTA. Third, the microtopographical and microenvironmental control on the liquid-solid interaction may lead to a critical design for PTA to provide soluble factors, nutrients, and gases to the cells embedded within the scaffold. We suggest that the level set numerical simulation method may be utilized to engineer the consistent circulation of bioactive liquid throughout the PTA microenvironment.

Animals↗

PubMedDate not supplied

Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue.

The FDA has approved the clinical use of recombinant bone morphogenetic proteins (BMPs). However, the use of recombinant BMPs in humans has required large doses of the proteins to be effective, which suggests that the delivery method of bone morphogenetic proteins needs to be optimized. Gene therapy is an alternative method to deliver such recombinant proteins, and gene transfer techniques have been tested on a variety of cell types including bone marrow cells, skin fibroblasts, peripheral blood monocytes, and muscle-derived cells. In this study, we sought to determine the ability of BMP-2-producing human adipose-derived mesenchymal stem cells to heal a critically sized femoral defect in a nude rat model. After approval by the human subjects protection committee, human adipose tissue was obtained from healthy donors. The lipoaspirate was processed as previously described (De Ugarte, D.A., et al. Cells Tissues Organs 174, 101, 2003). Cells were grown in culture and infected with a BMP-2-carrying adenovirus. Five million cells were applied to a collagen- ceramic carrier and implanted into femoral defects as previously described (Zuk, P.A., et al. Mol. Biol. 13, 4279, 2002). All animals were killed at 8 weeks. Femora were dissected out and underwent radiographic, histologic, and biomechanical analysis. Eleven of the 12 femora in the group treated with human processed lipoaspirate (HPLA) cells genetically modified to overexpress BMP-2 had healed at 8 weeks. This was assessed by radiographs, by mechanical testing, and by histology. The one femur that did not heal had a subacute infection. All eight of the femora treated with the rhBMP-2-impregnated collagen-ceramic carrier healed. No statistically significant difference was detected between these two groups. Evaluation of the control groups: group II (collagen- ceramic carrier with HPLA cells) and group III (collagen-ceramic carrier alone) showed that none of the femora had healed by 8 weeks. Our results indicate that HPLA cells genetically modified by adenoviral gene transfer to overexpress BMP-2 can induce bone formation in vivo and heal a critically sized femoral defect in an athymic rat. The HPLA cells alone did not induce significant bone formation. However, when combined with an osteoinductive factor these cells may be an effective method for enhancing bone healing and the tissue engineering of bone.

Adenoviridae↗