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Biomedical subjects

D A Grande

Publications and source records attributed to D A Grande.

At least 19 recordsLinked to original sources
PubMed2005

Sonic hedgehog gene-enhanced tissue engineering for bone regeneration.

Improved methods of bone regeneration are needed in the craniofacial rehabilitation of patients with significant bone deficits secondary to tumor resection, congenital deformities, and prior to prosthetic dental reconstruction. In this study, a gene-enhanced tissue-engineering approach was used to assess bone regenerative capacity of Sonic hedgehog (Shh)-transduced gingival fibroblasts, mesenchymal stem cells, and fat-derived cells delivered to rabbit cranial bone defects in an alginate/collagen matrix. Human Shh cDNA isolated from fetal lung tissue was cloned into the replication-incompetent retroviral expression vector LNCX, in which the murine leukemia virus retroviral LTR drives expression of the neomycin-resistance gene. The rat beta-actin enhancer/promoter complex was engineered to drive expression of Shh. Reverse transcriptase-polymerase chain reaction analysis demonstrated that the transduced primary rabbit cell populations expressed Shh RNA. Shh protein secretion was confirmed by enzyme-linked immunosorbent assay (ELISA). Alginate/ type I collagen constructs containing 2 x 10(6) Shh-transduced cells were introduced into male New Zealand White rabbit calvarial defects (8 mm). A total of eight groups (N=6) were examined: unrestored empty defects, matrix alone, matrix plus the three cell populations transduced with both control and Shh expression vectors. The bone regenerative capacity of Shh gene enhanced cells was assessed grossly, radiographically and histologically at 6 and 12 weeks postimplantation. After 6 weeks, new full thickness bone was seen emanating directly from the alginate/collagen matrix in the Shh-transduced groups. Quantitative two-dimensional digital analysis of histological sections confirmed statistically significant (P<0.05) amounts of bone regeneration in all three Shh-enhanced groups compared to controls. Necropsy failed to demonstrate any evidence of treatment-related side effects. This is the first study to demonstrate that Shh delivery to bone defects, in this case through a novel gene-enhanced tissue-engineering approach, results in significant bone regeneration. This encourages further development of the Shh gene-enhanced tissue-engineering approach for bone regeneration.

Adipose Tissue↗
PubMed2001

Treatment of ischemic wounds using cultured dermal fibroblasts transduced retrovirally with PDGF-B and VEGF121 genes.

The healing of ischemic wounds is a particularly difficult clinical challenge. In this study, rabbit dermal fibroblasts transduced retrovirally with human platelet-derived growth factor B (PDGF-B) and human vascular endothelial growth factor 121 (VEGF121) genes were used to treat wounds in a rabbit ischemic ear model. The PDGF-B and VEGF121 genes were obtained from human umbilical vein endothelial cells (HUVECs) by reverse transcription-polymerase chain reaction, cloned into retroviral vectors under control of the beta-actin promoter, and introduced into primary rabbit dermal fibroblast cells. In vitro results demonstrated that rabbit dermal fibroblasts are transduced and selected readily using retroviral vectors, and are engineered to secrete PDGF-B and VEGF121 at steady-state levels of 150 ng per 10(6) cells per 24 hours and 230 ng per 10(6) cells per 24 hours respectively. These cells were then seeded onto polyglycolic acid (PGA) scaffold matrices and used to treat ischemic rabbit ear wounds. Immunohistochemistry showed intense staining for PDGF-B and VEGF121 in the wounds treated with these transduced cells compared with the control treatment groups. For the relatively more ischemic distal ear wounds, granulation tissue deposition was increased significantly in the wounds treated with PDGF-B- and VEGF121-transduced cells compared with wounds treated with PGA alone. These results demonstrate that gene augmentation of rabbit dermal fibroblasts with the PDGF-B and VEGF121 genes introduced into this ischemic wound model via PGA matrices modulates wound healing, and may have clinical potential in the treatment of ischemic wounds.

Animals↗
PubMed2000

Extracellular matrix protein gene expression of bovine chondrocytes cultured on resorbable scaffolds.

It has been demonstrated that using cultured chondrocytes that have been seeded onto various biomatrices can enhance the quality of the articular cartilage repair tissue. As tissue-engineering becomes increasingly more complex there is a need to understand how a specific biomaterial may influence gene expression. In this study several commonly used scaffold materials for cartilage tissue engineering were evaluated with respect to their influence on matrix gene expression. Primary cultures of bovine chondrocytes were established in monolayer then seeded onto polylactic acid (PLLA), polyglycolic acid (PGA), collagen matrices. The induction of collagen type I, collagen type II, and aggrecan was observed at various time points on these biomaterials using RT-PCR. The collagen type I gene was upregulated on collagen scaffolds throughout the culture period. PLLA and PGA showed initial induction followed by downregulation. Monolayer culture did not induce collagen I message. Collagen II genes were selectively upregulated after 72 and 96 h post seeding depending the scaffold material. Monolayer culture had strong induction of collagen II. The aggrecan protein was consistently expressed in all scaffold materials cultures and monolayer.

Animals↗
PubMed2000

Cartilage and bone regeneration using gene-enhanced tissue engineering.

Joint cartilage injury remains a major problem in orthopaedics with more than 500,000 cartilage repair procedures performed yearly in the United States at a cost of hundreds of millions of dollars. No consistently reliable means to regenerate joint cartilage currently exists. The technologies of gene therapy and tissue engineering were combined using a retroviral vector to stably introduce the human bone morphogenic protein-7 complementary deoxyribonucleic acid into periosteal-derived rabbit mesenchymal stem cells. Bone morphogenic protein-7 secreting gene modified cells subsequently were expanded in monolayer culture, seeded onto polyglycolic acid grafts, implanted into a rabbit knee osteochondral defect model, and evaluated for bone and cartilage repair after 4, 8, and 12 weeks. The grafts containing bone morphogenic protein-7 gene modified cells consistently showed complete or near complete bone and articular cartilage regeneration at 8 and 12 weeks whereas the grafts from the control groups had poor repair as judged by macroscopic, histologic, and immunohistologic criteria. This is the first report of articular cartilage regeneration using a combined gene therapy and tissue engineering approach.

Animals↗
PubMed1999

Mechanically induced calcium waves in articular chondrocytes are inhibited by gadolinium and amiloride.

Chondrocytes in articular cartilage utilize mechanical signals from their environment to regulate their metabolic activity. However, the sequence of events involved in the transduction of mechanical signals to a biochemical signal is not fully understood. It has been proposed that an increase in the concentration of intracellular calcium ion ([Ca2+]i) is one of the earliest events in the process of cellular mechanical signal transduction. With use of fluorescent confocal microscopy, [Ca2+]i was monitored in isolated articular chondrocytes subjected to controlled deformation with the edge of a glass micropipette. Mechanical stimulation resulted in an immediate and transient increase in [Ca2+]i. The initiation of Ca2+ waves was abolished by removing Ca2+ from the extracellular media and was significantly inhibited by the presence of gadolinium ion (10 microM) or amiloride (1 mM), which have previously been reported to block mechanosensitive ion channels. Inhibitors of intracellular Ca2+ release (dantrolene and 8-diethylaminooctyl 3,4,5-trimethoxybenzoate hydrochloride) or cytoskeletal disrupting agents (cytochalasin D and colchicine) had no significant effect on the characteristics of the Ca2+ waves. These findings suggest that a possible mechanism of Ca2+ mobilization in this case is a self-reinforcing influx of Ca2+ from the extracellular media, initiated by a Ca2+-permeable mechanosensitive ion channel. Our results indicate that a transient increase in intracellular Ca2+ concentration may be one of the earliest events involved in the response of chondrocytes to mechanical stress and support the hypothesis that deformation-induced Ca2+ waves are initiated through mechanosensitive ion channels.

Amiloride↗
PubMed1999

Cartilage tissue engineering: current limitations and solutions.

Articular cartilage repair remains one of the most intensely studied orthopaedic topics. To date the field of tissue engineering has ushered in new methodologies for the treatment of cartilage defects. The authors' 10-year experience using principles of tissue engineering applied to resurfacing of cartilage defects is reported. Which cell type to use, chondrocytes versus chondroprogenitor cells, and their inherent advantages and disadvantages are discussed. Chondrocytes initially were used as the preferred cell type but were shown to have long term disadvantages in models used by the authors. Mesenchymal stem cells can be used effectively to overcome the limitations experienced with the use of differentiated chondrocytes. The use of mesenchymal stem cells as platforms for retroviral transduction of genes useful in cartilage repair introduces the concept of gene modified tissue engineering. The fundamental conditions for promoting and conducting a viable cartilage repair tissue, regardless of which cell type is used, also were studied. Placement of a synthetic porous biodegradable polymer scaffold was found to be a requirement for achieving an organized repair capable of functionally resurfacing a cartilage defect. A new modular device for intraarticular fixation of various graft composites has been developed. This new cartilage repair device is composed of bioabsorbable polymers and is capable of being delivered by the arthroscope.

Animals↗
PubMed1999

Gene-enhanced tissue engineering: applications for bone healing using cultured periosteal cells transduced retrovirally with the BMP-7 gene.

Periosteum has cell populations, including osteoprogenitor and chondroprogenitor cells, that can be grown in cell culture and form both bone and cartilage under appropriate conditions. The authors have shown previously that cultured periosteal cells can be used in the tissue engineering of bone, and they demonstrated substantial bone formation in a rabbit cranial defect model. In the current study, principles of tissue engineering were combined with principles of gene therapy to produce cultured periosteal cells transduced retrovirally with the bone morphogenetic protein 7 (BMP-7) gene to be used in the treatment of bone defects. Human BMP-7 complementary deoxyribonucleic acid was generated from a cell line using reverse transcription polymerase chain reaction and cloned into a retroviral vector plasmid. Retroviral vector particles were then used to transduce New Zealand White rabbit periosteal cells. Transduced periosteal cells demonstrated substantial production of both BMP-7 messenger ribonucleic acid by Northern blot analysis and BMP-7 protein by enzyme-linked immunosorbent assay. These cells were then seeded into polyglycolic acid (PGA) matrices and used to repair critical-size rabbit cranial defects. At 12 weeks, defect sites repaired with BMP-7-transduced periosteal cells/PGA had significantly increased radiographic and histological evidence of bone repair compared with those defect sites repaired with negative control-transduced cells/PGA, nontransduced cells/PGA, PGA alone, or unrepaired defects. Thus, this study demonstrates successfully a tissue engineering approach to bone repair using genetically modified cells.

Animals↗
PubMed1999

Gene-enhanced tissue engineering: applications for wound healing using cultured dermal fibroblasts transduced retrovirally with the PDGF-B gene.

The treatment of difficult wounds remains a considerable clinical challenge. The goal of this study was to determine whether genetic augmentation of dermal cells on resorbable matrices can stimulate the healing process, leading to increased tissue repair in a rat full-thickness excisional wound repair model. The human platelet-derived growth factor B (PDGF-B) gene was the initial gene chosen to test this hypothesis. The human PDGF-B gene was obtained from human umbilical vein endothelial cells (HUVEC) by reverse transcriptase-polymerase chain reaction, cloned into retroviral vectors under control of either the cytomegalovirus promoter or the rat beta-actin promoter, and introduced into primary rat dermal cells. In vitro results demonstrate that rat dermal cells are transduced and selected readily using retroviral vectors, and engineered to secrete PDGF-B at a steady-state level of approximately 2 ng per milliliter culture per 1 million cells per 24 hours. Seeding of the gene-modified cells onto polyglycolic acid (PGA) scaffold matrices and introduction into the rat model resulted in substantially increased fibroblast hypercellularity over control wounds at both 7 and 14 days posttreatment. Our results demonstrate that gene augmentation of rat dermal fibroblasts with the PDGF-B gene introduced into this animal model via PGA matrices modulates wound healing and suggests that experimentation with additional genes for use separately or in combination with PDGF-B for additional, improved wound healing is warranted.

Animals↗
PubMed1998

Diffusive properties of immature articular cartilage.

The diffusive properties of immature bovine articular cartilage were determined using two different-sized, uncharged solutes (glucose 180 Da, and dextran 10k Da). Radioactively tagged glucose and dextran were diffused into the cartilage for transport times of 5, 15, and 60 min, and the diffusion and partition coefficients were calculated by fitting the experimental data to a one-dimensional diffusion model. The diffusion and partition coefficients for the two solutes averaged 6.08 +/- 2.19 and 5.09 +/- 2.51 (x 10(-6) cm2/s) and 0.712 +/- 0.149 and 0.615 +/- 0.120, respectively. Both coefficients were significantly greater for glucose compared to the larger dextran. While no statistical differences could be found in the diffusive properties of these solutes in immature cartilage compared to their diffusive properties in mature cartilage, there was some evidence that the larger dextran solute might diffuse faster in the earlier time periods. Finally, the bulk fluid contents between the two types of cartilage were not different even though the immature tissue was significantly thicker (1.6 times) than the mature tissue. Our results indicate that the solute diffusion properties of articular cartilage, at least with respect to uncharged solutes, do not change during skeletal maturation.

Animals↗
PubMed1998

Expression of human bone morphogenic protein 7 in primary rabbit periosteal cells: potential utility in gene therapy for osteochondral repair.

A commonly encountered problem in orthopedics is bone and cartilage tissue injury which heals incompletely or without full structural integrity. This necessitates development of improved methods for treatment of injuries which are not amenable to treatment using current therapies. An already large and growing number of growth factors which play significant roles in bone remodeling and repair have been identified in the past few years. It is well established that bone morphogenic proteins induce the production of new bone and cartilage. An efficient method of delivery of these growth factors by conventional pharmacological means has yet to be elucidated. We wished to evaluate the use of retroviral vector-mediated gene transfer to deliver genes of therapeutic relevance for bone and cartilage repair. To determine the feasibility of using amphotropically packaged retroviral vectors to transduce primary rabbit mesenchymal stem cells of periosteal origin, primary periosteal cells were isolated from New Zealand white rabbits, transduced in vitro with a retroviral vector bearing both the nuclear localized lacZ marker gene and the neo(r) gene, and selected in G418. We used a convenient model for analysis of in vivo stability of these cells which were seeded on to polymer scaffold grafts and implanted into rabbit femoral osteochondral defects. The nuclear localized beta-galactosidase protein was expressed in essentially 100% of selected cells in vitro and was observed in the experimental explants from animals after both 4 and 8 weeks in vivo, while cells transduced with a retroviral vector bearing only the neo(r) gene in negative control explants showed no blue staining. We extended our study by delivering a gene of therapeutic relevance, human bone morphogenic protein 7 (hBMP-7), to primary periosteal cells via retroviral vector. The hBMP-7 gene was cloned from human kidney 293 cell total RNA by RT-PCR into a retroviral vector under control of the CMV enhancer/promoter. Hydroxyapatite secretion, presumably caused by overexpression of hBMP-7, was observed on the surface of the transduced and selected periosteal cells, however, this level of expression was toxic to both PA317 producer and primary periosteal cells. Subsequently, the strong CMV enhancer/promoter driving the hBMP-7 gene was replaced in the retroviral vector by a weaker enhancer/promoter from the rat beta-actin gene. Nontoxic levels of expression of hBMP-7 were confirmed at both the RNA and protein levels in PA317 producer and primary periosteal cell lines and cell supernatants. This work demonstrates the feasibility of using a gene therapy approach in attempts to promote bone and cartilage tissue repair using gene-modified periosteal cells on grafts.

Animals↗
PubMed1998

Tissue engineered bone repair of calvarial defects using cultured periosteal cells.

Periosteum has been demonstrated to have cell populations, including chondroprogenitor and osteoprogenitor cells, that can form both cartilage and bone under appropriate conditions. In the present study, periosteum was harvested, expanded in cell culture, and used to repair critical size calvarial defects in a rabbit model. Periosteum was isolated from New Zealand White rabbits, grown in cell culture, labeled with the thymidine analog bromodeoxyuridine for later localization, and seeded into resorbable polyglycolic acid scaffold matrices. Thirty adult New Zealand White rabbits were divided into groups, and a single 15-mm diameter full-thickness calvarial defect was made in each animal. In group I, defects were repaired using resorbable polyglycolic acid implants seeded with periosteal cells. In group II, defects were repaired using untreated polyglycolic acid implants. In group III, the defects were left unrepaired. Rabbits were killed at 4 and 12 weeks postoperatively. Defect sites were then studied histologically, biochemically, and radiographically. In vitro analysis of the cultured periosteal cells indicated an osteoblastic phenotype, with production of osteocalcin upon 1,25(OH)2 vitamin D3 induction. In vivo results at 4 weeks showed islands of bone in the defects repaired with polyglycolic acid implants with periosteal cells (group I), whereas the defects repaired with untreated polyglycolic acid implants (group II) were filled with fibrous tissue. Collagen content was significantly increased in group I compared with group II (2.90 +/- 0.80 microg/mg dry weight versus 0.08 +/- 0.11 microg/mg dry weight, p < 0.006), as was the ash weight (0.58 +/- 0.11 mg/mg dry weight versus 0.35 +/- 0.06 mg/mg dry weight, p < 0.015). At 12 weeks there were large amounts of bone in group I, whereas there were scattered islands of bone in groups II and III. Radiodensitometry demonstrated significantly increased radiodensity of the defect sites in group I, compared with groups II and III (0.740 +/- 0.250 OD/mm2 versus 0.404 +/- 0.100 OD/mm2 and 0.266 +/- 0.150 OD/mm2, respectively, p < 0.05). Bromodeoxyuridine label, as detected by immunofluorescence, was identified in the newly formed bone in group I at both 4 and 12 weeks, confirming the contribution of the cultured periosteal cells to this bone formation. This study thus demonstrates a tissue-engineering approach to the repair of bone defects, which may have clinical applications in craniofacial and orthopedic surgery.

Absorptiometry, Photon↗
PubMed1997

Evaluation of matrix scaffolds for tissue engineering of articular cartilage grafts.

Injury to articular cartilage predisposes that joint to further degeneration and eventually osteoarthritis. Recent studies have demonstrated the feasibility of using chondrocytes together with different biomaterial carriers as grafts for the repair of cartilage defects. The following study was undertaken to determine the effect of a variety of these materials on chondrocyte growth and extracellular matrix synthesis. We cultured chondrocytes on several commonly used materials and compared their rates of synthesis of proteoglycan and collagen. Additionally, we evaluated them in a closed culture recirculating system on these materials and compared them with standard culture techniques. This was done to see whether such a bioreactor-type system can be used to enhance the quality of in vitro reconstructed tissues. Our results demonstrated marked variability with respect to how chondrocytes responded to culture on the various materials. Bioabsorbable polymers such as polyglycolic acid (PGA)--enhanced proteoglycan synthesis, whereas collagen matrices stimulated synthesis of collagen. The use of the closed culture system, in general, improved the rates of synthesis of collagen and proteoglycan on the different material scaffolds. Exceptions were collagen synthesis on collagen matrices: use of the closed culture system did not enhance the rate of synthesis. Rates of proteoglycan synthesis on PGA scaffold initially was higher in the closed culture system but did not sustain a difference over the entire course of the 3-week culture period. This study demonstrates the importance of carrier material for the purpose of cartilage tissue reconstruction in vitro.

Biocompatible Materials↗
PubMed1995

Chondrocytes isolated from mature articular cartilage retain the capacity to form functional gap junctions.

The distribution, expression, and functionality of gap junctions was examined in bovine chondrocytes (BCs) isolated from mature articular cartilage. BC cells displayed immunoreactivity for connexin 43 (Cx43), a specific gap junction protein. Cx43 protein expression was confirmed by Western blot analysis, and Cx43 mRNA was detected by nuclease protection assay. Additionally, BCs were shown to be functionally coupled, as revealed by dye transfer studies, and octanol, a gap junction uncoupler, greatly attenuated coupling. Furthermore, confocal microscopy of fluo-3 loaded BC cells revealed that deformation-induced cytosolic Ca2+ ion (Ca2+) signals propagated from cell-to-cell via gap junctions. To our knowledge, this is the first evidence suggesting that chondrocytes isolated from adult articular cartilage express functional gap junctions.

Animals↗
PubMed1994

Joint resurfacing using allograft chondrocytes and synthetic biodegradable polymer scaffolds.

Cartilage implants which could potentially be used to resurface damaged joints were created using rabbit articular chondrocytes and synthetic, biodegradable polymer scaffolds. Cells were serially passaged and then cultured in vitro on fibrous polyglycolic acid (PGA) scaffolds. Cell-PGA constructs were implanted in vivo as allografts to repair 3-mm diameter, full thickness defects in the knee joints of adult rabbits, and cartilage repair was assessed histologically over 6 months. In vitro, chondrocytes proliferated on PGA and regenerated cartilaginous matrix. Collagen and glycosaminoglycan (GAG) represented 20 to 8% of the implant dry weight (dw), respectively, at the time of in vivo implantation; the remainder was PGA and unspecified components. Implants based on passaged chondrocytes had 1.7-times as much GAG and 2.6-times as much collagen as those based on primary chondrocytes. In vivo, cartilaginous repair tissue was observed after implantation of PGA both with and without cultured chondrocytes. Six month repair was qualitatively better for cell-PGA allografts than for PGA alone, with respect to: 1) surface smoothness, 2) columnar alignment of chondrocytes, 3) spatially uniform GAG distribution, 4) reconstitution of the subchondral plate, and 5) bonding of the repair tissue to the underlying bone. These pilot studies demonstrate that it is feasible to use cell-polymer allografts for joint resurfacing in vivo.

Animals↗
PubMed1994

Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects.

Cartilage resurfacing by chondrocyte implantation, with fibrin used as a vehicle, was examined in large (12 mm) full-thickness articular cartilage defects in horses. Articular chondrocytes, isolated from a 9-day-old foal, were mixed with fibrinogen and injected with thrombin, in a 1:1 mixture, into 12 mm circular defects on the lateral trochlea of the distal femur of eight normal horses. The contralateral femoropatellar (knee) joint served as a control in which the defect was left empty. Synovial fluid from the femoropatellar joints was sampled on days 0, 4, 7, 30, 120, and 240 postoperatively. Groups of four horses were killed at 4 or 8 months postoperatively, and the repair tissue was evaluated by gross and histologic examination with use of hematoxylin and eosin and safranin O staining and by autoradiography. Biochemical analyses included quantitation of proteoglycan, total collagen, and type-II collagen in the repair tissue. Grossly, grafted defects had improved filling of the cartilage lesions; histologically, these areas consisted of differentiated chondrocytes in the deep and middle zones. The cellular arrangement in these zones resembled that of hyaline cartilage. The control defects contained poorly attached fibrous tissue throughout. Grafted tissue at 8 months had increased proteoglycan synthesis evident by both safranin O staining and autoradiography. Glycosaminoglycan quantitation by dye-binding assay confirmed a significantly elevated glycosaminoglycan content in grafted defects (58.8 micrograms/mg of dry weight) compared with control defects (27.4 micrograms/mg; p < 0.05). Similarly, the levels of chondroitin sulfate/dermatan sulfate was significantly elevated in the grafted defects, and this was the predominant glycosaminoglycan epitope present. There was a statistically significant (p < 0.05) increase in type-II collagen in the grafted tissue at 8 months (61.2% grafted; 25.1% control). This resurfacing attempt with use of allograft chondrocytes, secured in large full-thickness articular defects with polymerized fibrin, resulted in an improved cartilage surface in comparison with the control defects, a significantly greater aggrecan level, and a significantly higher proportion of type-II collagen.

Animals↗
PubMed1992

The effect of low-level Nd:YAG laser energy on adult articular cartilage in vitro.

Reports of laser energy applied to soft tissues in vitro and in vivo suggest both stimulation and inhibition of specific metabolic processes, depending on the type of laser, the energy density (ED) used, the mode of delivery, and type of tissue studied. An earlier in vitro study of Nd:YAG laser irradiation of articular cartilage indicated stimulation of both matrix and DNA synthesis for 6 days following laser exposure. In vivo reports on the ability of Nd:YAG laser energy to stimulate the healing of partial-thickness cartilage defects are conflicting. In the present study, a noncontact continuous-wave Nd:YAG laser beam of varying EDs was applied to full-thickness adult articular cartilage explants maintained in organ culture; the metabolic processes of chondrocyte DNA synthesis and matrix synthesis were followed over 2 weeks. For both canine and bovine cartilage, low-levels of laser energy (ED 51-127 J/cm2) stimulated matrix synthesis at 6-7 days following laser exposure, with a concomitant decrease in baseline DNA synthesis. By 12-14 days, however, these dose-dependent effects were no longer seen, with no significant differences from control noted for any of the laser energies studied. Histologic analysis of the cartilage explants following laser exposure showed no significant differences in cell number or morphology between sample and control groups; however, a decrease in matrix proteoglycan staining was seen in the highest laser energy group at all time points. These findings indicate that exposure to low-level noncontact Nd:YAG laser energy promotes a significant stimulation of cartilage matrix synthesis. However, a single exposure may not be sufficient to promote a sustained upregulation of cartilage metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗