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Biomedical subjects

Jeffrey O Hollinger

Publications and source records attributed to Jeffrey O Hollinger.

5 recordsLinked to original sources

Porous polymer scaffolds surface-modified with arginine-glycine-aspartic acid enhance bone cell attachment and differentiation in vitro.

This study was designed to determine if the surface modification of porous poly(lactic acid) (PLA) scaffolds would enhance osteogenic precursor cell (OPC) attachment, growth, and differentiation. A covalently grafted amino group (-NH(2)), poly(L-lysine) (PLL), and the peptide arginine-glycine-aspartic acid (RGD) were selected for the evaluation. The hypothesis was that surface modification would have a positive impact on cell-substratum interactions. The experiment was performed by OPC cells being placed on PLA films and scaffolds modified with NH(2), PLL, or RGD in tissue culture media. OPC attachment to PLA films was assessed after 24 h of incubation. The growth and differentiation of the adherent OPCs on porous PLA scaffolds were assessed after 14 and 28 days for alkaline phosphatase (APase) activity and calcium levels, both of which increase as OPCs differentiate into mature bone cells. All assays were accomplished in triplicate, and data were tested with post hoc orthogonal contrasts (i.e., Fisher's least significant difference) at p < or = 0.05. The PLA film surface-modified with RGD showed better OPC cell attachment than the other films. The cells on the PLA scaffolds surface-modified with RGD also exhibited an increase in APase activity and calcium levels in comparison with those on other scaffolds. This difference was apparent at both time intervals and was especially evident in the tissue culture media containing an osteogenic supplement. The results of this study indicate that modifying the surface of PLA polymer scaffolds with RGD enhances bone cell attachment and differentiation and may improve their ability to regenerate bone tissue more efficiently in wound models.

Absorbable Implants↗

Fabrication of poly(alpha-hydroxy acid) foam scaffolds using multiple solvent systems.

The present studies describe the fabrication and characterization of highly porous and interconnected poly(alpha-hydroxy acid) foam scaffolds produced using a phase separation multisolvent system, followed by a sublimation process. Fabrication parameters, including solvent composition, polymer concentration, freezing temperature, polymer type, and polymer molecular weight, were optimized to produce the desired foam microstructure. Analyses of selected samples with scanning electron microscopic images and mercury intrusion porosimetry indicated polymer foams with pore size ranges of 100-350 microm, a porosity >90%, and an interconnecting open-pore foam structure. Scaffold degradation profiles varied according to the type and molecular weight of the polymers. Cytocompatibility assays demonstrated that the preferred foam structures were nontoxic and osteoprecursor cells seeded into the scaffolds exhibited the ability to attach, propagate, and differentiate into a calcified structure.

Absorbable Implants↗

Transverse process fusion with bovine anorganic bone.

A biodegradable collagen membrane and bovine anorganic bone were studied in a rabbit spine fusion model. The bovine, anorganic bone is a nonantigenic, acellular clinical product used as a bone substitute for dento-alveolar applications. We reasoned this product with a collagen membrane could be useful for spine fusions. Our hypothesis was that bovine, anorganic bone, and a collagen membrane would promote spine fusion equivalent to an autogenous bone graft. To test the hypothesis, the transverse processes of the fourth and fifth lumbar vertebrae were decorticated in 30 rabbits divided equally among five groups. In one group, following decortication, no treatment was administered, whereas in the remaining four groups, treatments consisted of either autograft, collagen membrane, anorganic bone, or anorganic bone plus collagen membrane. Rabbits were euthanized 6 weeks after surgery, and the lumbar vertebrae were removed, radiographed, and processed for histology. The radiographs and histological sections were subjected to quantitative morphometric analyses and post hoc statistical testing (p < or = 0.05). We determined anorganic bone without a collagen membrane migrated into the soft tissues contiguous to the transverse processes. However, with a collagen membrane, the anorganic bone remained at the implant site, causing an osseous fusion of the transverse processes. Although the autograft promoted the greatest amount of new bone formation, significant transverse process fusion was accomplished with the anorganic bone and collagen membrane. Additional longer term studies are contemplated to validate feasibility of this clinical option, including a biomechanical component.

Animals↗

Synthesis, biodegradability, and biocompatibility of lysine diisocyanate-glucose polymers.

The success of a tissue-engineering application depends on the use of suitable biomaterials that degrade in a timely manner and induce the least immunogenicity in the host. With this purpose in mind, we have attempted to synthesize a novel nontoxic biodegradable lysine diisocyanate (LDI)- and glucose-based polymer via polymerization of highly purified LDI with glucose and its subsequent hydration to form a spongy matrix. The LDI-glucose polymer was degradable in aqueous solutions at 37, 22, and 4 degrees C, and yielded lysine and glucose as breakdown products. The degradation products of the LDI-glucose polymer did not significantly affect the pH of the solution. The physical properties of the polymer were found to be adequate for supporting cell growth in vitro, as evidenced by the fact that rabbit bone marrow stromal cells (BMSCs) attached to the polymer matrix, remained viable on its surface, and formed multilayered confluent cultures with retention of their phenotype over a period of 2 to 4 weeks. These observations suggest that the LDI-glucose polymer and its degradation products were nontoxic in vitro. Further examination in vivo over 8 weeks revealed that subcutaneous implantation of hydrated matrix degraded in vivo three times faster than in vitro. The implanted polymer was not immunogenic and did not induce antibody responses in the host. Histological analysis of the implanted polymer showed that LDI-glucose polymer induced a minimal foreign body reaction, with formation of a capsule around the degrading polymer. The results suggest that biodegradable peptide-based polymers can be synthesized, and may potentially find their way into biomedical applications because of their biodegradability and biocompatibility.

Biocompatible Materials↗

Composition options for tissue-engineered bone.

The logical assembly of tissue-engineered bone is ultimately directed by the clinical status of the patient. The basic elements for tissue-engineered bone should include signaling molecules, cells, and extracellular matrix. The assembly of these basic elements may need to be modified by tissue engineers to account for patient variables of age, gender, health, systemic conditions, habits, and anatomical implant. Moreover, different regions of the body will have different functional loads and vascularity. This review discusses several basic options that may be necessary to engineer bone, including spatial and temporal assembly of signaling factors, cells, and biomimetic extracellular matrices. Moreover, the importance of the health care status of the patient who may be receiving the tissue-engineered composition is emphasized.

Bone Marrow Cells↗