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Biomedical subjects

Daniel A Grande

Publications and source records attributed to Daniel A Grande.

7 recordsLinked to original sources
PubMed2006

Clinical applications of bioactive factors in sports medicine: current concepts and future trends.

The ability to biologically manipulate musculoskeletal healing and augment bone and soft tissue repair and regeneration holds great promise. Advances in the basic science study and clinical application of bioactive proteins and growth factors continues to evolve. Improvement in the surgical resurfacing of articular cartilage defects and tendon and ligament repair through the addition of bioactive polypeptides is currently underway. The purpose of this article is to review the present array of biologically active materials that may be clinically applicable in sports medicine and arthroscopy. Mechanisms for biologic augmentation of tissue repair and regeneration will be discussed. Current limitations and future considerations will be reviewed particularly as they relate to practical clinical approaches.

Arthroscopy↗
PubMed2006

Mesenchymal stem cells in tissue engineering.

The repair of diseased or damaged cartilage remains one of the most challenging problems of musculoskeletal medicine. Tissue engineering advances in cartilage repair have utilized autologous and allogenic chondrocyte and cartilage grafts, biomaterial scaffolds, growth factors, stem cells, and genetic engineering. The mesenchymal stem cell has specifically attracted much attention because of its accessibility, potential for differentiation, and manipulability to modern molecular, tissue and genetic engineering techniques. Mesenchymal stem cells provide invaluable tools for the study of tissue repair when combined with a carrier vehicle/matrix scaffold, and/or bioactive growth factors. However, an underappreciated source of knowledge lies in the relationship between fetal development and adult tissue repair. The multitude of events that take place during fetal development which lead from stem cell to functional tissue are poorly understood. A more thorough understanding of the events of development as they pertain to cartilage organogenesis may help elucidate some of the unknowns of adult tissue repair.

Animals↗
PubMed2003

Gene therapy and tissue engineering in repair of the musculoskeletal system.

Historically, surgeons have sought and used different procedures in order to augment the repair of various skeletal tissues. Now, with the completion of the Human Genome Project, many researchers have turned to gene therapy as a means to aid various ailments. In the orthopedic field, many strides have been made toward using gene therapy and tissue engineering in a clinical setting. In this review, several studies are outlined in different areas that gene therapy has or will influence orthopedic surgery. Gene therapy and tissue engineering can aid in fracture healing and spinal fusions by inducing bone formation, ligamentous repairs by increasing the production of connective tissue fibers, intervertebral disc disease by creating potential replacements, and articular cartilage repairs by providing means to improve cartilage. As we continue to see great contributions, such as the few mentioned here, this field will continue to mature and develop.

Animals↗
PubMed2003

Accelerated diabetic wound healing using cultured dermal fibroblasts retrovirally transduced with the platelet-derived growth factor B gene.

The treatment of diabetic wounds is a considerable clinical challenge. In this study, mouse dermal fibroblasts retrovirally transduced with the human platelet-derived growth factor B (PDGF-B) gene were used to treat diabetic mouse wounds. The PDGF-B gene was obtained from human umbilical vein endothelial cells, cloned into retroviral vectors, and introduced into diabetic mouse C57B1/ks-db/db dermal fibroblasts. In vitro results demonstrated production of PDGF-B protein by these transduced cells at steady-state levels of 1000 ng PDGF-B/10(6) cells/24 hours, and expression of PDGF-B mRNA. These cells were seeded onto polyglycolic acid scaffold matrices and used to treat diabetic mouse 20-mm x 20-mm full-thickness excisional dorsal skin wounds. Measurement of the residual epithelial gap at 21 days showed significantly accelerated healing (P < 0.05) of wounds treated with PDGF-transduced cells (epithelial gap 10.46 +/- 1.20 mm) compared with untreated wounds (14.66 +/- 0.591 mm), wounds treated with polyglycolic acid alone (14.80 +/- 0.575 mm), or wounds treated with negative control LNCX-transduced cells (13.76 +/- 0.831 mm). Immunohistochemical staining showed intense staining for PDGF in wounds treated with PDGF-B-transduced cells. This study demonstrates the promising potential for gene therapy in diabetic wound healing.

Animals↗
PubMed2003

Stem cells as platforms for delivery of genes to enhance cartilage repair.

BACKGROUND: The long-held axiom put forth by Hunter in 1743, that cartilage once injured is incapable of healing, has been challenged by the technique of autologous chondrocyte transplantation. This conceptual change in the way in which orthopaedists are approaching the problem of cartilage repair has spawned a myriad of new and innovative treatment modalities. This review will focus on the new techniques and directions that our facility and other investigators are exploring to restore functional articular cartilage. METHODS: To show the usefulness and effectiveness of local tissue-engineered gene therapy, we transduced periosteal stem cells known to have osteochondral potential with either bone morphogenetic protein-7 (BMP-7) or sonic hedgehog (Shh) gene. These cells were cultured to increase the number of cells and then were seeded onto bioresorbable polymer scaffolds. Full-thickness osteochondral defects were created in the mid-trochlear region of eighty New Zealand White rabbits, and the implants containing the transduced cells were placed in the defects. Animals were killed at six, eight, twelve, and twenty-six weeks postoperatively and were examined macroscopically and histologically. RESULTS: Periosteal-derived cambium-layer cells proliferated rapidly and were easily used for transfection of both the bone morphogenic protein-7 (BMP-7) and sonic hedgehog (Shh) genes. The control defects became filled with a mixture of fibrous and fibrocartilaginous tissue. The addition of either the BMP-7 or the Shh gene significantly enhanced the quality of the repair tissue, resulting in a much smoother surface and more hyaline-appearing cartilage. There was, however, a noticeable difference in the persistence of the cartilage phase between the group that received the Shh gene and the group that received the BMP-7 gene, with the subchondral compartment in the latter group seeming to remodel with bone much faster. CONCLUSION AND CLINICAL RELEVANCE: The results of these experiments clearly demonstrate the utility of tissue-engineering strategies in which gene therapy is used to locally influence the repair environment. It is interesting to note the relative differences in the two different gene responses with regard to skeletal development and the repair process. These differences could be related to the genes' temporal patterns in skeletal development.

Animals↗
PubMed2002

In vitro characteristics of cultured posterior longitudinal ligament tissue.

STUDY DESIGN: To determine the osteogenicity of posterior longitudinal ligament ossification, the posterior longitudinal ligament obtained during anterior cervical surgery from patients with the disorder was analyzed with in vitro cultures. OBJECTIVES: To determine the osteogenicity of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: The osteogenicity of posterior longitudinal ligament ossification in North America requires better documentation. METHODS: The posterior longitudinal ligament obtained during anterior cervical corpectomy with fusion from seven patients, three with ossification of the posterior longitudinal ligament documented by magnetic resonance imaging and computed tomography and four with spondylosis, was blindly submitted for in vitro culture. Explants of the posterior longitudinal ligament were placed in Dulbecco modified Eagle medium with 10% fetal calf serum, antibiotics, 4 mmol/L x L-proline, and 50 mg/L ascorbic acid. After reaching confluency, cells were trypsinized, and first-passage cells were used for all osteocalcin measurements to establish their osteoblastic phenotype. Periosteal cells, previously shown to synthesize osteocalcin, were used as a positive control. The cells were incubated with 1,25(OH)2 vitamin D3 at 10E-8 M for 72 hours in serum-free medium. The supernatants were collected and frozen, after which the quantity of osteocalcin induced by exposure to 1,25(OH)2 vitamin D3 was determined using enzyme-linked immunoassay. Control replicate cultures were measured without incubation using vitamin D3. RESULTS: Ossification of the posterior longitudinal ligament cell lines responded positively with osteocalcin synthesis in the 0.1 to 0.4 ng/M range. The cell line of the patient with spondylosis alone did not respond to vitamin D3 priming. CONCLUSIONS: Posterior longitudinal ligament cells from the three North American white patients with ossification of the posterior longitudinal ligament, when cultured in vitro, synthesized osteocalcin on vitamin D3 priming, confirming their osteoblastic phenotype, whereas posterior longitudinal ligament cells from four white patients with isolated spondylosis did not.

Calcitriol↗