Biomedical subjects

F H Fu

Publications and source records attributed to F H Fu.

At least 37 records · Page 2Linked to original sources

PubMed2001

Muscle-based gene therapy and tissue engineering.

The development of new biological approaches based on cell and gene therapies, in combination with tissue engineering, may create innovative ways to treat various tissues of the musculoskeletal system. It is vital for practicing orthopaedic surgeons to understand the terminology, fundamental concepts, and current research in this burgeoning field so that they may practice their discipline in its fullest form. Such techniques, coupled with advances in cell biology and polymer chemistry, are resulting in novel approaches to treating musculoskeletal disorders in which surgeons, who have traditionally used the tools of excision and reconstruction to treat patients, may now serve as surgical gardeners who create microenvironments that are conducive for tissue regeneration. Gene therapy and tissue engineering applications for bone healing, articular disorders, and skeletal muscle diseases and injuries are currently being explored. This review is intended to update readers on the principles and current advances in muscle-based gene therapy and tissue engineering for the musculoskeletal system.

Animals↗

PubMed2000

GAG-augmented polysaccharide hydrogel: a novel biocompatible and biodegradable material to support chondrogenesis.

The quality of articular cartilage engineered using a cell-polymer construct depends, in part, on the chemical composition of the biomaterial and whether that biomaterial can support the chondrocytic phenotype. Acknowledging the supportive influence of tissue-specific matrix molecules on the chondrocytic phenotype, we have combined chondroitin sulfate-A (CSA) and chitosan, a glycosaminoglycan (GAG) analog, to develop a novel biomaterial to support chondrogenesis. Chitosan is a polycationic repeating monosaccharide of beta-1,4-linked glucosamine monomers with randomly located N-acetyl glucosamine units. Chitosan may be combined with the polyanionic CSA such that ionic crosslinking results in hydrogel formation. Bovine primary articular chondrocytes, when seeded onto a thin layer of CSA-chitosan, form discrete, focal adhesions to the material and maintain many characteristics of the differentiated chondrocytic phenotype, including round morphology, limited mitosis, collagen type II, and proteoglycan production. Our findings suggest CSA-chitosan may be well suited as a carrier material for the transplant of autologous chondrocytes or as a scaffold for the tissue engineering of cartilage-like tissue.

Animals↗

PubMed2000

Importance of the medial meniscus in the anterior cruciate ligament-deficient knee.

The incidence of meniscal tears in the chronically anterior cruciate ligament-deficient knee is increased, particularly in the medial meniscus because it performs an important function in limiting knee motion. We evaluated the role of the medial meniscus in stabilizing the anterior cruciate ligament-deficient knee and hypothesized that the resultant force in the meniscus is significantly elevated in the anterior cruciate ligament-deficient knee. To test this hypothesis, we employed a robotic/universal force-moment sensor testing system to determine the increase in the resultant force in the human medial meniscus in response to an anterior tibial load following transection of the anterior cruciate ligament. We also measured changes in the kinematics of the knee in multiple degrees of freedom following medial meniscectomy in the anterior cruciate ligament-deficient knee. In response to a 134-N anterior tibial load, the resultant force in the medial meniscus of the anterior cruciate ligament-deficient knee increased significantly compared with that in the meniscus of the intact knee; it increased by a minimum of 10.1 N (52%) at full knee extension to a maximum of 50.2 N (197%) at 60 degrees of flexion. Medial meniscectomy in the anterior cruciate ligament-deficient knee also caused a significant increase in anterior tibial translation in response to the anterior tibial load, ranging from an increase of 2.2 mm at full knee extension to 5.8 mm at 60 degrees of flexion. Conversely, coupled internal tibial rotation in response to the load decreased significantly, ranging from a decrease of 2.5 degrees at 15 degrees of knee flexion to 4.7 degrees at 60 degrees of flexion. Our data confirm the hypothesis that the resultant force in the medial meniscus is significantly greater in the anterior cruciate ligament-deficient knee than in the intact knee when the knee is subjected to anterior tibial loads. This indicates that the demand on the medial meniscus in resisting anterior tibial loads is increased in the anterior cruciate ligament-deficient knee compared with in the intact knee, suggesting a mechanism for the increased incidence of medial meniscal tears observed in chronically anterior cruciate ligament-deficient patients. The large changes in kinematics due to medial meniscectomy in the anterior cruciate ligament-deficient knee confirm the important role of the medial meniscus in controlling knee stability. These findings suggest that the reduction of resultant force in the meniscus may be a further motive for reconstructing the anterior cruciate ligament, with the goal of preserving meniscal integrity.

Aged↗

PubMed2000

Mechanical behavior of two hamstring graft constructs for reconstruction of the anterior cruciate ligament.

We compared the mechanical behavior of two common hamstring graft constructs that are frequently used for reconstruction of the anterior cruciate ligament-Graft A: quadrupled semitendinosus tendon fixed with titanium button/polyester tape and suture/screw post, and Graft B: a double semitendinosus and double gracilis tendon fixed with a cross pin and two screws over washers. The experimental protocol used to evaluate each graft construct included stress relaxation (with and without preconditioning), cyclic loading, and a tensile load-to-failure test. The amount of stress relaxation without preconditioning was 60.6% for Graft A and 53.8% for Graft B. With preconditioning, it significantly decreased (p < 0.05) to 48.7 and 42.3%, respectively. Elongation of the graft construct in response to 100 cycles of loading (20-150 N) was 1.8 and 0.6% of the original length for Grafts A and B, respectively. However, after a series of five cyclic loading tests, the residual permanent elongation for each construct was 3.8 +/- 1.2 and 0.3 +/- 0.2 mm, a significant difference (p < 0.05) between the two graft constructs. Further analysis found more than 90% of the permanent elongation in the proximal and distal regions of Graft A, which consisted of polyester tape tied to a titanium button (proximal) and sutures tied around a screw post (distal). The tensile load-to-failure tests also revealed significant differences (p < 0.05) between the two graft constructs. Linear stiffness was 32 +/- 1 and 119 +/- 19 Nmm and ultimate load was 415 +/- 36 and 658 +/- 128 N for Grafts A and B, respectively. For Graft A, the polyester tape consistently failed; for Graft B, slippage or tearing from the washers was the mode of failure. We conclude that a quadruple-hamstring graft fixed over a cross pin proximally and with metal washers distally (Graft B) has less permanent elongation in response to cyclic loading and has structural properties superior to those of a graft construct that includes suture and tape material (Graft A). The large permanent elongation following repetitive loading of a graft construct with tape and suture material during the early postoperative period is of concern.

Aged↗

PubMed2000

[TGF-beta-1 gene transfer in joint cartilage cells. Stimulating effect in extracellular matrix synthesis].

TGF beta-1 has been shown to upregulate matrix synthesis in articular chondrocytes. TGF beta-gene transfer to chondrocytes has the potential to increase the local production of this key component within regenerating cartilage after trauma and could support the repair process in articular cartilage lesions. Primary rabbit articular chondrocytes were cultured and retrovirally transfected with the experimental TGF beta-1 and the lacZ marker gene for control purposes. After radioactive labeling of new synthesized matrix proteins results were compared with normal primary chondrocytes. After TGF beta-1 gene transfer the endogenous growth factor concentration was doubled compared to normal chondrocytes and decreased in the lacZ control group. The proteoglycan synthesis in TGF beta-1 transfected chondrocytes showed a 96% increase compared to the basal production of normal chondrocytes. The LacZ transfected group revealed the opposite effect by a 44% decrease. The collagen synthesis of TGF beta-1 transfected chondrocytes was 304% compared to normal chondrocytes, predominantly type II collagen. The lacZ group collagen production was reduced by 35%. We conclude that TGF beta-1 gene transfer overcomes the decreasing effect observed by transfection with the LacZ marker gene and increases matrix synthesis in articular chondrocytes. Genetically altered chondrocytes might improve the repair of cartilage lesions by stimulating matrix synthesis and supporting the expression of the hyaline phenotype.

Animals↗

PubMed2000

Technical innovation: creation of a peripheral vascularized trough to enhance healing in cryopreserved meniscal allograft reconstruction.

The important functions of the meniscus have been well described. Lack of a meniscus may lead to instability and early osteoarthrosis of the knee. Meniscal transplantation is an option following complete or subtotal meniscectomy in symptomatic patients with correct alignment, and mild to moderate chondrosis with the goal of preventing further degenerative sequelae to the knee. Since the first meniscus allograft implantation was performed 1984, there have been reported several open and arthroscopic techniques. We present our technique of arthroscopically assisted transplantation of a cryopreserved meniscal allograft with special consideration given to the technical details of this procedure. This technique employs creation of a circumferential osseocancellous trough in combination with transosseous tibial tunnel fixation and arthroscopic suture passage to both secure and enhance healing of the meniscal allograft.

Humans↗

PubMed2000

Peroneal nerve palsy following knee dislocation: pathoanatomy and implications for treatment.

Peroneal nerve palsy following knee dislocation is a serious problem, and neurolysis at the time of knee reconstruction does not always result in return of peroneal nerve function. We describe peroneal nerve pathoanatomy in three patients in whom late exploration of the peroneal nerve was performed because of ongoing absence of ankle dorsiflexion. We identified frank nerve rupture in two patients and a lengthy neuroma in continuity in one which extended far proximal to the fibular head and well above the previous surgical incision used for peroneal nerve neurolysis at the time of knee reconstruction. In light of the current state of microneural surgery and the potential to reconstruct nerve defects, we discuss how our findings impact on treatment, and provide recommendations which may improve recovery of peroneal nerve function in future cases.

Adult↗

PubMed2000

Gene therapy for meniscal injury: enhanced synthesis of proteoglycan and collagen by meniscal cells transduced with a TGFbeta(1)gene.

Objective To determine whether meniscal cells can express a TGFbeta(1)transgene delivered by a retroviral vector, and respond to the gene product by increasing matrix synthesis. Methods Monolayer cultures of human and canine meniscal cells were infected with retroviruses carrying either a human TGFbeta(1)cDNA or marker genes. Conditioned media were assayed for the presence of TGFbeta(1). Biosynthesis assays using radiolabeled precursors were employed to determine the effects of the transgenes on the synthesis of proteoglycan, collagen and noncollagenous proteins. Collagen phenotyping was performed by SDS-PAGE. Results Media conditioned by canine and human meniscal cells transduced with the TGFbeta(1)gene, accumulated several nanograms/10(6)cells of TGFbeta(1)during a 48 h incubation. Media conditioned by control cells contained very little TGFbeta(1). Transduction with the TGFbeta(1)gene, but not marker genes, increased the synthesis of collagen and proteoglycan by 8-15-fold. The synthesis of noncollagenous proteins was enhanced more modestly. Monolayers of meniscal cells synthesized types I, III, V and VI collagen. The TGFbeta(1)gene increased the synthesis of all types of collagen without altering the ratios between them. Conclusions Meniscal cells are readily transduced by retroviral vectors and respond to the transfer of a TGFbeta(1)cDNA by greatly increasing matrix synthesis. These findings encourage the further development of genetic approaches to the healing of meniscal lesions.

Animals↗

PubMed2000

Ulnar nerve elongation and excursion in the cubital tunnel after decompression and anterior transposition.

We studied the elongation and excursion of cadaveric ulnar nerves during elbow flexion in control conditions and after in situ decompression and anterior subcutaneous transposition. We found that the normal nerve had the greatest elongation (23%) and excursion (14 mm) in the epicondylar groove. Decompression did not alter the excursion, but significantly reduced the elongation in the groove (6%) and increased it proximally (19%). After anterior subcutaneous transposition, the nerve segment which was originally in the groove elongated with elbow extension to the same extent as occurred with the normal nerve during flexion.

Aged↗

PubMed2000

Process analysis in outpatient knee surgery: effects of regional and general anesthesia on anesthesia-controlled time.

BACKGROUND: The performance of anesthetic procedures before operating room entry (e.g., with either general or regional anesthesia [RA] induction rooms) should decrease anesthesia-controlled time in the operating room. The authors retrospectively studied the associations between anesthesia techniques and anesthesia-controlled time, evaluating one surgeon performing a single procedure over a 3-yr period. The authors hypothesized that, using the anesthesia care team model, RA would be associated with reduced anesthesia-controlled time compared with general anesthesia (GA) alone or combined general-regional anesthesia (GA-RA). METHODS: The authors queried an institutional database for 369 consecutive patients undergoing the same procedure (anterior cruciate ligament reconstruction) performed by one surgeon over a 3-yr period (July 1995 through June 1998). Throughout the period of study, anesthesia staffing consisted of an attending anesthesiologist medically directing two nurse anesthetists in two operating rooms. Anesthesia-controlled time values were compared based on anesthesia techniques (GA, RA, or GA-RA) using one-way analysis of variance, general linear modeling using time-series and seasonal adjustments, and chi-square tests when appropriate. P < 0. 05 was considered significant. RESULTS: RA was associated with the lowest anesthesia-controlled time (11.4 +/- 1.3 min, mean +/- 2 SEM). GA-RA (15.7 +/- 1.0 min) was associated with lower anesthesia-controlled time than GA used alone (20.3 +/- 1.2 min). CONCLUSIONS: When compared with GA without an induction room for outpatients undergoing anterior cruciate ligament reconstruction, RA with an induction room was associated with the lowest anesthesia- controlled time. Managers must weigh the costs and time required for anesthesiologists and additional personnel to place nerve blocks or induce GA preoperatively in such a staffing model.

Adult↗

PubMed2000

Use of growth factors to improve muscle healing after strain injury.

Muscle injuries represent a large number of professional and recreational sports injuries. Muscle strains habitually occur after an eccentric contraction, which often leads to an injury located in the myotendinous junction. Treatment varies widely, depending on the severity of the trauma, but has remained limited mostly to rest, ice, compression, elevation, antiinflammatory drugs, and mobilization. The authors' research group aims to develop new biologic approaches to improve muscle healing after injuries, including muscle strains. To achieve this goal, the authors investigated several parameters that will lead to the development of new strategies to enhance muscle healing. The authors first evaluated natural muscle healing after strain injuries and showed that muscle regeneration occurs in the early phase of healing but becomes impaired with time by the development of tissue fibrosis. Several growth factors capable of improving muscle regeneration were investigated; basic fibroblast growth factor, insulin-like growth factor, and nerve growth factors were identified as substances capable of enhancing muscle regeneration and improving muscle force in the strained injured muscle. The current study should aid in the development of strategies to promote efficient muscle healing and complete recovery after strain injury.

Animals↗

PubMed2000

Growth factors improve muscle healing in vivo.

Injury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury. Our findings showed that b-FGF, IGF and to a less extent NGF enhanced muscle regeneration in vivo compared with control muscle. At one month, muscles treated with IGF-1 and b-FGF showed improved healing and significantly increased fast-twitch and tetanus strengths. Our results suggest that b-FGF and IGF-1 stimulated muscle healing and may have a considerable effect on the treatment of muscle injuries.

Animals↗

PubMed1999

In situ force distribution in the glenohumeral joint capsule during anterior-posterior loading.

Our objective was to examine the function of the glenohumeral capsule and ligaments during application of an anterior-posterior load by directly measuring the in situ force distribution in these structures as well as the compliance of the joint. We hypothesized that interaction between different regions of the capsule due to its continuous nature results in a complex force distribution throughout the glenohumeral joint capsule. A robotic/universal force-moment sensor testing system was utilized to determine the force distribution in the glenohumeral capsule and ligaments of intact shoulder specimens and the joint kinematics resulting from the application of external loads at four abduction angles. Our results suggest that the glenohumeral capsule carries no force when the humeral head is centered in the glenoid with the humerus in anatomic rotation. However, once an anterior-posterior load is applied to the joint, the glenohumeral ligaments carry force (during anterior loading, the superior glenohumeral-coracohumeral ligaments carried 26+/-16 N at 0 degrees and the anterior band of the inferior glenohumeral ligament carried 30+/-21 N at 90 degrees). Therefore, the patient's ability to use the arm with the humerus in anatomic rotation should not be limited following repair procedures for shoulder instability because the repaired capsuloligamentous structures should not carry force during this motion. Separation of the capsule into its components revealed that forces are being transmitted between each region and that the glenohumeral ligaments do not act as traditional ligaments that carry a pure tensile force along their length. The interrelationship of the glenohumeral ligaments forms the biomechanical basis for the capsular shift procedure. The compliance of the joint under our loading conditions indicates that the passive properties of the capsule provide little resistance to motion of the humerus during 10 mm of anterior or posterior translation with anatomic humeral rotation. Finally, this knowledge also enhances the understanding of arm positioning relative to the portion of the glenohumeral capsule that limits translation during examination under anesthesia.

Aged↗

PubMed1999

Hamstring graft motion in the femoral bone tunnel when using titanium button/polyester tape fixation.

The objective of this study was to determine the relative motion of a quadruple hamstring graft within the femoral bone tunnel (graft-tunnel motion) under tensile loading. Six graft constructs were prepared from the semitendinosus and gracilis tendons of human cadavers and were fixed with a titanium button and polyester tape within a bone tunnel in a cadaveric femur. Three different lengths of polyester tape (15, 25, and 35 mm loops) were evaluated. The femur was held stationary and uniaxial tensile loads were applied to the distal end of the graft using a materials testing machine. Each construct was subjected to loading for ten cycles with upper limits of 50 N, 100 N, 200 N and 300 N. Graft-tunnel motion was then determined using the distances between reflective tape markers placed on the hamstring graft and at the entrance to the femoral bone tunnel, which were tracked with a high-resolution video system. Graft-tunnel motion was found to range from 0.7 +/- 0.2 mm to 3.3 +/- 0.2 mm, and significant increases in graft-tunnel motion were observed with increasing tensile loads (P < 0.05). Shorter tape length (15 mm) resulted in significantly less motion when compared to longer tape length (35 mm) (P < 0.05). We conclude that graft-tunnel motion is significant and should be considered when using this fixation technique. Early stress on the graft, as seen in postoperative rehabilitation exercises and athletic activities, may cause large graft-tunnel motion before graft incorporation is complete. A shorter distance between the tendon tissue and the titanium button is recommended to minimize the amount of graft-tunnel motion. Alternative fixation materials to polyester tape, or different fixation techniques, need to be developed such that graft-tunnel motion can be reduced. Further studies are needed to evaluate the effect of graft-tunnel motion on graft incorporation in the bone tunnel.

Biomechanical Phenomena↗

PubMed1999

Proprioception in the posterior cruciate ligament deficient knee.

This study was undertaken to evaluate knee proprioception in patients with isolated unilateral posterior cruciate ligament (PCL) injuries. Eighteen subjects with isolated PCL tears were studied 1-234 months after injury. The threshold to detect passive motion (TTDPM) was used to evaluate kinesthesia and the ability to passively reproduce passive positioning (RPP) to test joint position sense. Two starting positions were tested in all knees: 45 degrees (middle range) and 110 degrees (end range) to evaluate knee proprioception when the PCL is under different amounts of tension. TTDPM and RPP were tested as the knee moved into flexion and extension from both starting positions. A statistically significant reduction in TTDPM was identified in PCL-injured knees tested from the 45 degrees starting position, moving into flexion and extension. RPP was statistically better in the PCL-deficient knee as tested from 110 degrees moving into flexion and extension. No difference was identified in the TTDPM starting at 110 degrees or in RPP with the presented angle at 45 degrees moving into flexion or extension. These subtle but statistically significant findings suggest that proprioceptive mechanoreceptors may play a clinical role in PCL-intact and PCL-deficient patients. Further, it appears that kinesthesia and joint position sense may function through different mechanisms.

Adult↗

PubMed1999

Posterior peripheral sutures in meniscal allograft replacement.

In our experience, meniscal allograft transplantation does have a role after a total or a significant partial meniscectomy in young to middle-aged symptomatic patients. While the quality of the meniscal tissue is crucial to the success of the operation, it is equally important to duplicate the mechanical function of the original semilunar cartilage and assure a secure peripheral attachment of the meniscal implant. The technique for peripheral meniscal suture placement described in this article permits an easier and more secure attachment of the posterior third of the implant to the joint capsule.

Adult↗

PubMed1999

Use of muscle cells to mediate gene transfer to the bone defect.

Segmental bone defects and nonunions are relatively common problems facing all orthopaedic surgeons. Osteogenic proteins, i.e., BMP-2, can promote bone healing in segmental bone defects. However, a large quantity of the human recombinant protein is needed to enhance the bone healing potential. Cell mediated gene therapy in the bone defect can allow a sustained expression of the osteogenic proteins and further enhance bone healing. Muscle cells can be easily isolated and cultivated, and they are known to be an efficient gene delivery vehicle to muscle and nonmuscle tissues. Furthermore, they are capable of transforming into osteoblasts when stimulated by BMP-2. Thus, the utilization of muscle cells as the gene delivery vehicle to a bone defect would be an important step in establishing a less invasive treatment for non-unions and segmental bone defects. Muscle cells were transduced when the adenoviral-lacZ vector and injected into the bone defect and the muscles surrounding the defect. Expression of the marker gene was visualized 7 days after the injection, both macroscopically and microscopically, using lacZ histochemistry. The lacZ expressing cells in the defect tissue were also stained for desmin, a muscle specific marker, indicating the presence of muscle cells that have fused into myofibers in this nonmuscle bone defect area. With successful myoblast mediated gene delivery into the segmental bone defect, future experiments would focus on delivering viral vectors expressing osteogenic proteins to eventually improve bone healing postinjury.

Animals↗

PubMed1999

Direct-, fibroblast- and myoblast-mediated gene transfer to the anterior cruciate ligament.

The anterior cruciate ligament (ACL) has poor capabilities of healing. Maturation or "ligamentization" of the ACL following autograft or allograft reconstruction has been found slow and remains under investigation. In vitro and in vivo studies have shown that platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), and epidermal growth factor (EGF) have the potential to improve ligament healing. Gene therapy approaches may represent a new alternative in delivering these specific growth factors to the ACL. The aim of this study was to investigate the feasibility of three different gene therapy approaches (direct-, fibroblast-, and myoblast-mediated gene transfer) to the ACL. Rabbit myoblasts and ACL-fibroblasts were transduced with 5 x 10(7) recombinant adenoviral particles carrying the LacZ reporter gene (MOI = 50). Myoblasts and fibroblasts (1 x 10(6)) were each injected into the right ACL of 10 adult rabbits; direct injection of 5 x 10(7) adenoviral particles was performed in 10 other rabbits. The left side was used as sham. The beta-galactosidase production was revealed using the LacZ histochemical technique. The transduced fibroblasts and myoblasts were found in the ligament tissue and in the synovial tissue surrounding the ACL at 4, 7, 14, and 21 days postinjection. The myoblasts fused and formed myotubes in the ligament. The direct approach also allowed the transfer of the marker gene in the ligament at 4, 7, 21, and 42 days postinjection. X-gal staining revealed no expression of beta-galactosidase in the sham ligament. The presence of cells expressing the marker gene in the ACL opens up the possibility of delivering proteins (i.e., PDGF, TGF-beta, and EGF) capable of improving ACL healing and graft maturation. Furthermore, engineered myoblasts may mediate and accelerate the intraligament neovascularization. This new technology based on gene therapy and tissue engineering may allow a persistent expression of selected growth factors to enhance ACL healing following injury.

Adenoviridae↗