Intrinsic versus extrinsic vascularization in tissue engineering.
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Animals↗
Biomedical subjects
Alexander D Bach
Publications and source records attributed to Alexander D Bach.
Tissue engineering of injectable muscle: three-dimensional myoblast-fibrin injection in the syngeneic rat animal model.
BACKGROUND: Surgical treatment of skeletal muscle loss resulting from trauma, tumor ablation, or inborn tissue defects is hampered by the scarcity of functional substitute tissue. By using techniques of tissue engineering, reconstitution of skeletal muscle defects might become a more viable option. However, it is necessary to develop an adequate, practical method for delivering myoblasts within a three-dimensional scaffold in vivo. The aim of this study was to create and evaluate a novel method for the transfer of myoblasts with clinically approved components within a three-dimensional matrix. METHODS: The authors injected expanded primary male myoblasts into muscle defects in female syngeneic rats using a two-way syringe (Duploject) within a three-dimensional fibrin matrix. Detection and evaluation were performed using Y chromosome in situ hybridization, antidesmin immunostaining, and hematoxylin and eosin staining. To identify possible differences by means of integration, the injected myoblasts were compared with 7 days of precultivated constructs. RESULTS: Injected myoblasts showed increasing integration into host muscle fibers in a time-dependent manner, exclusively at the injection site. Antidesmin staining revealed a conserved myogenic phenotype of transplanted cells. The fibrin matrix resolved over a period of 12 weeks, with no indication of an inflammatory reaction. No significant difference in the number of detected Y chromosome-positive nuclei was found between the two transplantation groups. CONCLUSIONS: The presented technique of myoblast-fibrin injection indicates a clinical potential for reconstruction of skeletal muscle defects in vivo using a ready-to-use device in combination with tissue-engineering methods.
Animals↗
Vacuum application increases therapeutic safety and allows intensified local radiation treatment of malignant soft-tissue tumors.
PURPOSE: In order to simplify and improve outcome of radiation therapy and final defect coverage in patients suffering from invasive soft-tissue tumors, brachytherapy and application of V.A.C.uum-assisted closure (V.A.C.) were combined with delaying flap incision. PATIENTS AND METHODS: Two patients were excised as radically as possible and brachytherapy tubes were implanted directly on the tumor bed. At the same time, flaps for later defect coverage were preconditioned by circumcision. Brachytherapy and external- beam irradiation were performed directly on the vacuum sponge followed by subsequent defect coverage with the preconditioned flaps. RESULTS: Excision significantly reduced tumor masses in both patients; in one case sensible and motor function of the involved extremity was clearly improved. V.A.C. coverage allowed repeated brachytherapy and external-beam applications following exact placing of plastic tubes and FLABs on the tumor bed. Sequential irradiation had no effect on neighboring flap tissues, which healed without impairment following transposition. CONCLUSION: Combination of V.A.C. and brachytherapy can effectively replace circumstantial and laborious IORT (intraoperative radiotherapy) procedures. Exact placement of tubes on the tumor bed without subsequent tissue coverage is conserving preconditioned flap tissues, which are transposed for final defect coverage at the end of radiotherapy. However, by circumventing radiation exposure of these tissues, a possible later irradiation sequence can be performed without endangering defect-covering flaps.
Adult↗
Delayed reverse sural flap for staged reconstruction of the foot and lower leg.
BACKGROUND: Soft-tissue defects of the foot and lower leg caused by traumatic injury, tumor ablation, or infection associated with osteomyelitis often require coverage by flaps. One excellent option for reconstruction of these defects is the distally based neurofasciocutaneous sural flap. It allows rapid and reliable coverage of defects from the distal third of the lower leg to the forefoot without significant functional donor-site morbidity. However, the maximal size of the flap is limited by the delicate perfusion of the arterial network associated with the superficial sensory nerve. Delay procedures may increase the reliability of large sural flaps. METHODS: The authors successfully used delayed sural flaps based on a two-step procedure for the treatment of 11 patients (three women and eight men, age 50.1 +/- 20.0 years) with osteomyelitis (n = 3), melanoma (n = 3), sarcoma (n = 1), squamous cell carcinoma (n = 1), posttraumatic defects (n = 2), and recurrent gouty ulcer (n = 1). The delay period ranged from 7 to 15 days (9.7 +/- 3.1), the length of the flap was from 9 to 19 (14.8 +/- 3.0) cm, and the width of the flap from 7 to 12 (9.2 +/- 1.3) cm. Temporary wound coverage was achieved by vacuum-assisted closure during the delay period. RESULTS: All defects were covered successfully without major complications. CONCLUSIONS: The delay procedure positively affects the viability of large sural neurofasciocutaneous flaps. The authors recommend this modification for patients with large defects at the distal third of the lower leg or foot, requiring a two-step surgical approach due to the underlying disease.
Adult↗
The versatility of the free osteocutaneous fibula flap in the reconstruction of extremities after sarcoma resection.
BACKGROUND: An understanding of the biology of bone and soft-tissue sarcomas, knowledge of adjuvant therapies and refinement in techniques of reconstructive surgery have allowed limb-sparing and limb salvage surgery to become a reality in the management of malignant tumors of the extremities. Functional limb salvage following radical resection has become a possibility in many resectable tumors by the use of alloplastic prostheses, homograft or autogenous bone for skeletal reconstitution combined with vascularized soft tissue coverage. Although the free fibula flap has been well described for reconstructions of the mandible and oral cavity, it has not been widely presented as an ideal tool to preserve extremities and to circumvent amputation. PATIENTS AND METHODS: We describe the complex surgical reconstruction in four patients with primary sarcomas of the extremities. The sarcomas (Ewing's sarcoma, osteosarcoma and epitheloid sarcoma) were resected radically and the massive bone and soft tissue defect was replaced by vascularized free fibula transfer. RESULTS: We present our experience with versatility of this osteocutaneous flap to allow reconstruction and salvage of extremitity sarcomas. There were no operative or postoperative complication and all the four patients had good limb function. The flap was found to be versatile as it could be used for either upper limb or lower limb and for large defects. The results were better in upper limb than in lower limb. CONCLUSIONS: Free fibular graft was found to be effective for salvaging limb function where a massive bone defect resulted from wide tumor resection in the extremities.
Journal Article↗
Accelerated wound healing by in vivo application of keratinocytes overexpressing KGF.
Epidermal regeneration is a complex process, strongly influenced by growth factors, including keratinocyte growth factor (KGF). The objective of this study was to establish immortalized HaCaT keratinocytes and KMST-6-fibroblasts stably expressing KGF. Transfection efficiency, genomic integration, and functionality of the transgene were determined by ELISA and PCR, and KGF-expressing clones were selected using an air-liquid interface test system. HaCaT cells displayed stronger transgene expression compared to transfected fibroblasts, and the most effective HaCaT clone was incubated on a membrane carrier to form a "membrane cell graft." Twenty-one superficial second-degree burn wounds were created in each of three pigs, and wound healing capacity of the generated "polypeptide cell delivery system" after grafting was examined. Untransfected HaCaT keratinocytes and membrane-covered and untreated burn wounds served as controls. Histological and macroscopical follow-up revealed that grafting of transfected HaCaT cells resulted in complete reepithelialization within 5 days, while wounds covered with untransfected cells needed 2 days longer. At untreated sites, a thin epithelium was detectable after 10 days. The results indicate that wound healing processes can be stimulated distinctly by growth factors secreted from HaCaT cells, with a prominent role for transgenic KGF.
Animals↗
Applied tissue engineering in the closure of severe burns and chronic wounds using cultured human autologous keratinocytes in a natural fibrin matrix.
Whereas in severe burns cultured human epithelial cells may well serve as a life saving method, the true value of tissue-engineered skin products in chronic wound care has yet to be clearly defined. Among other well-known clinical problems, the engraftment rate of commercially available multilayered "sheet grafts" has been shown to vary extremely. Adherence of transplanted cells to the wound bed--especially in the presence of potential wound contamination-- is one of the crucial aspects of this technique. Keratinocyte suspensions in a natural fibrin sealant matrix can potentially treat a variety of skin defects. In acute burn wounds, as well as in chronic wounds the clinical application of this type of tissue-engineered skin substitute demonstrates the capacity of cultured human autologous keratinocytes in a fibrin sealant matrix to adhere to wound beds, attach and spread over the wound resulting in reepithelialization of both acute and chronic wounds. In full thickness burns the combination of this new tool with allogenic dermis is a promising option to achieve complete dermal-epidermal reconstitution by means of tissue engineering and guided tissue repair. When transferring this technique into the treatment of chronic wounds we found an optimal preparation of such recipient wound beds to be crucial to the success. The additional application of continuous negative pressure (vacuum therapy) and preliminary chip skin grafting to optimally prepare the recipient site may be helpful tools to achieve such well-prepared and graftable surfaces. Prospective controlled comparative studies should be designed to further assess the clinical efficacy of this technique.
Burns↗
Buried chip skin grafting in neuropathic diabetic foot ulcers following vacuum-assisted wound bed preparation: enhancing a classic surgical tool with novel technologies.
In patients with diabetes mellitus, complications such as polyneuropathy and peripheral angiopathy inevitably lead to diabetic foot complications including foot ulcers, gangrene, and osteoarthropathy. These conditions necessitate minor or major amputation as part of treatment. In patients with Charcot's arthropathy and predominant neuropathy, recurrent foot ulcers are common in areas of high pressure. Such high pressure is caused by the degrading of the architecture of the foot and inadequate footwear. These patients are a clinical challenge. A select group of such patients may benefit from free surgical tissue transfer, though free or local flap surgery is often difficult or even impossible owing to an impaired arterial circulation. In such wounds, surgical debridement followed by skin grafts often fail due to bacterial burden in the wounds. To circumvent these problems, the authors developed a therapeutic approach using buried chip skin grafting to close granulation wound beds in diabetic feet. Locally applied vacuum therapy (VAC) for wound bed preparation of chronic, nonresponsive foot ulcers and subsequent grafting using the burying technique with a minute fraction of skin was used. Firm closure was achieved. The closed wound was resistant to mechanical irritation.
Journal Article↗
Pectus excavatum breast and chest deformity: indications for aesthetic plastic surgery versus thoracic surgery in a multicenter experience.
BACKGROUND: Breast and chest wall disfiguration attributable to a funnel chest is an aesthetically and sometimes functionally debilitating deformity requiring surgical correction. Whereas extensive and combined deformities of the ventral chest wall are classically corrected using a so-called minimally invasive repair of the pectus excavatum, a modified Ravitch repair, or the minimized Erlangen repair, plastic surgeons are mostly challenged with alloplastic implant corrections of mild funnel chests. The authors have introduced an endoscopic method for placement of customized implants to restore the visible and nonfunctionally disturbing deformation of mild funnel chests when only the sternal plate is involved. This study compared these different plastic surgical and thoracic surgical approaches in a multicenter experience to develop a clinical algorithm and to identify those patients not requiring bony correction but rather alloplastic endoscopic implant correction alone. METHODS: Patients with deformed rib cages and sternal plates were treated with the Erlangen minimally invasive procedure or a modified Ravitch procedure. For deformities involving the sternal bones only, endoscopically assisted minimally invasive implantation of silastic implants was performed. RESULTS: Between 1987 and 2003, 599 patients with a pectus excavatum deformity were treated surgically by the authors' group. Between 1999 and 2003, 515 patients underwent surgery using the Erlangen minimally invasive repair technique at Friedrich-Alexander University-Erlangen. In addition, 84 patients underwent surgery at the Freiburg University Medical Center. In the current series, 79 patients underwent surgery using the modified Ravitch method. The mean patient age was 20.5 years (range, 3-54 years), and the rate of postoperative relapses was 5%. The findings showed that 73% of the patients judged the aesthetic result as excellent to good, and 20% were satisfied. In contrast, only five patients were suitable for soft tissue augmentation only. Two of these patients in the initial period received custom implants presternally via classical transverse skin incisions, whereas three patients were treated with endoscopic customized implant tissue augmentation. CONCLUSION: Whereas with combined deformity of the sternal plate and the rib cage, a modified Ravitch repair yields good results, the endoscopic soft tissue correction with customized implants helps to avoid unsightly scars, allows for safe hemostasis in the dissection pocket, and leads to enhanced patient satisfaction. In the case of major chest wall deformity with orthopedic and functional relevance, a combination of the minimally invasive procedures (e.g., endoscopic correction and Erlangen repair) seems to show both optimized cosmetic results and maximized functionality.
Adolescent↗
Tissue engineering of cultured skin substitutes.
Skin replacement has been a challenging task for surgeons ever since the introduction of skin grafts by Reverdin in 1871. Recently, skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements. This has been fostered by the dramatically improved survival rates of major burns where the availability of autologous normal skin for grafting has become one of the limiting factors. The ideal properties of a temporary and a permanent skin substitute have been well defined. Tissue-engineered skin replacements: cultured autologous keratinocyte grafts, cultured allogeneic keratinocyte grafts, autologous/allogeneic composites, acellular biological matrices, and cellular matrices including such biological substances as fibrin sealant and various types of collagen, hyaluronic acid etc. have opened new horizons to deal with such massive skin loss. In extensive burns it has been shown that skin substitution with cultured grafts can be a life-saving measure where few alternatives exist. Future research will aim to create skin substitutes with cultured epidermis that under appropriate circumstances may provide a wound cover that could be just as durable and esthetically acceptable as conventional split-thickness skin grafts. Genetic manipulation may in addition enhance the performance of such cultured skin substitutes. If cell science, molecular biology, genetic engineering, material science and clinical expertise join their efforts to develop optimized cell culture techniques and synthetic or biological matrices then further technical advances might well lead to the production of almost skin like new tissue-engineered human skin products resembling natural human skin.
Animals↗