Biomedical subjects

Jamal A Nazzal

Publications and source records attributed to Jamal A Nazzal.

4 recordsLinked to original sources

PubMed2005

Producing a flexible tissue-engineered cartilage framework using expanded polytetrafluoroethylene membrane as a pseudoperichondrium.

BACKGROUND: Both native and engineered cartilage is brittle and fractures easily without perichondrium. The aim of this study was to understand the role of the perichondrium and try to enhance the flexible properties of tissue-engineered cartilage using expanded polytetrafluoroethylene (ePTFE) membrane as a pseudoperichondrium. METHODS: The study was conducted in two phases. In phase I, native swine auricular cartilage of different thicknesses was studied by histologic evaluation and failure testing. Next, isolated perichondrium was bonded to native cartilage slices using fibrin glue or Dermabond and tested to failure. In phase II, swine auricular chondrocytes were suspended in fibrin glue. The chondrocyte-fibrin glue composites were then bound to expanded polytetrafluoroethylene membrane in two trilaminar configurations: In group EC-1, the membrane was in the center, whereas it was on the surfaces in group EC-2. Specimens were implanted into nude mice for 4 weeks, 8 weeks, 12 weeks, and 8 months and subjected to histologic evaluation and failure testing. RESULTS: In phase I, the results demonstrated that perichondrium securely bonded to the cartilage plays an important role in maintaining the flexible nature of elastic cartilage. In phase II, failure testing revealed that specimens in group EC-1 (expanded polytetrafluoroethylene core) were fractured during bending and destroyed after torsion, whereas those in group EC-2 (cartilage core) returned to their original shape without fracturing even after rigorous torsion. Histologic analysis demonstrated that transplanted chondrocytes penetrated into the microporous structure of expanded polytetrafluoroethylene and created a bond to it. CONCLUSION: It is possible to engineer flexible cartilage using expanded polytetrafluoroethylene as a pseudoperichondrium.

Animals↗

PubMed2004

Heterotopic limb allotransplantation model to study skin rejection in the rat.

Current rodent models for investigation of limb allotransplantation typically utilize orthotopic whole-limb transplantation, a morbid and time-consuming procedure. Our objective was to design a less morbid rat model to explore the immunological obstacles of limb transplantation, and particularly skin. Twenty lower hindlimbs from 10 donors were transplanted into a heterotopic subcutaneous position into 20 animals (10 isogeneic and 10 allogeneic). Each group was further subdivided to include animals with (n = 5) and without (n = 5) a skin paddle for observation of cutaneous signs of rejection. All grafts in the isogeneic group survived for 100 days, i.e., the endpoint of the study. Allogeneic transplants rejected their allografts at a mean of 12.8 days (with skin) and 20.6 days (without). Our heterotopic limb transplantation model takes less time and is less stressful to the animals, while allowing for early observation of graft skin rejection, when compared to orthotopic whole-limb transplantation.

Anastomosis, Surgical↗

PubMed2004

Prolongation of skin allograft survival after neonatal injection of donor bone marrow and epidermal cells.

Composite-tissue (e.g., hand allograft) allotransplantation is currently limited by the need for immunosuppression to prevent graft rejection. Inducing a state of tolerance in the recipient could potentially eliminate the need for immunosuppression but requires reprogramming of the immunological repertoire of the recipient. Skin is the most antigenic tissue in the body and is consistently refractory to tolerance induction regimens using bone marrow transplantation alone. It was hypothesized that tolerance to skin allografts could be induced in rats by injecting epidermal cells with bone marrow cells during the first 24 hours of life of the recipients. Brown Norway rats (RT1n) served as donors for the epidermal cells, bone marrow cells, and skin grafts. Epidermal cells were injected intraperitoneally and bone marrow cells were injected intravenously into Lewis (RT1l) newborn recipient rats. In control groups, recipients received saline solution with no cells (group I, n = 12), bone marrow cells only (group II, n = 15), or epidermal cells only (group III, n = 15). In the experimental group (group IV, n = 18), recipients received epidermal and bone marrow cells simultaneously. Skin grafts were transplanted from Brown Norway (RT1n) rats to the Lewis (RT1l) rats 8 weeks after cell injections. Skin grafts survived an average of 8.5 days in group I (10 grafts), 9.2 days in group II (12 grafts), and 12 days in group III (14 grafts). Grafts survived 15.5 days (8 to 26 days) in group IV (15 grafts). The difference was statistically significant (p < 0.05). Hair growth was observed in some accepted grafts in group IV but never in the control groups. This is the first report of prolonged survival of skin allografts in a rat model after epidermal and bone marrow cell injections. Survival prolongation was achieved across a major immunological barrier, without irradiation, myeloablation, or immunosuppression. It is concluded that the presentation of skin-specific antigens generated a temporary state of tolerance to the skin in the recipients that could have delayed the rejection of skin allografts.

Animals↗

PubMed2003

Split tolerance to a composite tissue allograft in a swine model.

BACKGROUND: The antigenicity of skin is a major obstacle to expanding human composite tissue transplantation. For example, multiple rejection episodes of the skin have been noted in clinical hand transplant patients. We have previously demonstrated tolerance to vascularized musculoskeletal allografts in major histocompatibility complex (MHC)-matched miniature swine treated with 12 days of cyclosporine. This regimen did not reproducibly lead to tolerance to subsequent frozen donor skin grafts. However, such skin grafts did not have a primary vascular supply. The aim of this study was to determine if tolerance to limb allografts with a vascularized skin component could be achieved with MHC matching and a 12-day course of immunosuppression. METHODS: Hind limb grafts harvested with a 100 cm(2) cutaneous paddle were transplanted heterotopically into six MHC-matched, minor antigen-mismatched miniature swine. All animals received a 12-day course of cyclosporine. One control animal was not immunosuppressed. Grafts were evaluated with biweekly biopsies and tissue viability determined by histologic analysis. To test for sensitization, frozen donor skin grafts were applied to all animals that survived to postoperative day 100. RESULTS: All treated animals (n=6) were tolerant to their musculoskeletal allografts at the time of necropsy (>100 days) regardless of the status of the epidermis. One animal demonstrated tolerance to the skin for more than 180 days. The other five animals demonstrated prolonged survival of the epidermal portion of the graft. The control animal rejected the graft epidermis at 10 days postoperatively. Frozen donor skin grafts demonstrated accelerated rejection (<10 days) in three of the animals and led to simultaneous rejection of both the epidermis of the allograft and the skin graft in the long-term tolerant animal. The rejection of the skin grafts did not break tolerance to the musculoskeletal portion in any of the animals. CONCLUSIONS: All animals exhibited indefinite survival of the musculoskeletal portion of their allografts but only prolonged survival of the epidermis. The loss of the graft skin appears to be the result of an isolated immune reaction to the skin, and, in particular, the epidermis. This observation is further substantiated by the accelerated rejection of secondarily placed frozen donor skin grafts.

Animals↗