Composite Tissue Grafts Research Articles

Ex Vivo Transfer of Adenovirus-Mediated CTLA4Ig Gene Combined with a Short Course of Rapamycin Therapy Prolongs Free Flap Allograft Survival

Adenovirus-mediated cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (AdCTLA4Ig) gene transfer has been reported to enhance both organ and composite tissue grafts survival in rodent transplantation models. The authors tested the efficacy of local expression of CTLA4Ig gene on the survival of rat free flap allografts. Brown Norway rat groin flaps were transplanted in Lewis rat recipients. The donor flaps were perfused ex vivo with AdCTLA4Ig via the afferent artery before transplantation. The distribution and duration of CTLA4Ig transgene expression in the flaps were assessed by immunohistochemical staining and semiquantitative reverse transcriptase polymerase chain reaction after transplantation. A mixed lymphocyte reaction was performed to test the antigen-specific immune response. Flow cytometry was used to detect the variations of CD4+25+Foxp3+ T cells in recipients' spleens. Immunohistochemical staining and reverse transcriptase polymerase chain reaction demonstrated expression of CTLA4Ig transgene in AdCTLA4Ig-perfused free flap allografts. AdCTLA4Ig-perfused free flap allografts survived significantly longer compared with survival of enhanced green fluorescent protein adenovirus-perfused free flap allografts. When combined with a short course of rapamycin, the survival time of AdCTLA4Ig-perfused free flap allografts was remarkably prolonged. The mixed lymphocyte reaction results indicate that ex vivo transfer of AdCTLA4Ig induces antigen-specific unresponsiveness. AdCTLA4Ig perfusion did not change the proportion of CD4+25+Foxp3+ T cells in recipients' spleens. The authors demonstrated that a singular ex vivo perfusion of AdCTLA4Ig gene induced efficient transduction of the flaps and, when combined with a short course of rapamycin, promoted the remarkably longer survival of flap allografts.

Application of autologous dermal-fat flap in repair of collapsed nasal dorsum

Objective To investigate the feasibility, rationality and efficacy of the autologous dermal-fat composite tissue used as filling materials in the repair of nasal dorsum collapse.Methods The dermal fat composite tissue block (7.0 cm× 1.0 cm × 1.0 cm) was removed from the buttocks or abdoman as filling materials. 13 cases of nasal dorsum and nasal-shaped misfits were treated by using an umbrella graft of the auricular cartilage plus dermal-fat composite tissue graft to reconstruct natual shape of nasal dorsum and tip. Results The nasal dorsum and tip were repaired in 13 patients with collapsed nasal dorsum. The dermal-fat composite tissue survived well, and the incisions were healed in stage Ⅰ and the incision trace was not obvious. After follow-up for one year, the shape of nose was much satisfactory. Conclusion It is a well-accepted and easy-going procedure to repair collapsed nasal dorsum with autologous dermal-fat or a combination of composite ear cartilage tissue graft, with satisfactory effect and no rejection reactions. Key words: Dorsum collapse; Repair; Dermal-fat composite tissue; Auricular cartilage

Neck mass secondary to pedicle ossification after oromandibular reconstruction

Conclusions: Development of a firm neck mass after treatment of head and neck cancer often indicates recurrent tumor. Heterotopic ossification has not been previously reported as a potential etiology of neck masses after fibula free flap oromandibular reconstruction in the head and neck surgery literature. The radiographic incidence of this phenomenon is high, while the clinical incidence of neck masses secondary to heterotopic ossification is low. Heterotopic ossification can be distinguished from recurrent tumor on the basis of physical examination, radiographic assessment, and/or fine needle aspiration biopsy. Awareness of heterotopic ossification should be included in the differential diagnosis of patients with a neck mass who have undergone fibula free flap reconstructions. Review of a patient database of 520 consecutive fibula free flaps between 1995-2010 revealed sixtysix patients who had postoperative CT scans of the neck available for radiographic review. Of the 66 patients who had postoperative CT scans available for radiologic assessment, 43/66 (65%) showed heterotopic ossification of the fibula periosteum. In an effort to elucidate risk factors for heterotopic ossification, statistical analysis was used to interpret the data. There was no difference in frequency of males and females between in patients with heterotopic ossification (p = 0.4). The mean ages of patients with radiographic evidence (58.3 years) of ossification and those without radiographic evidence of ossification (63.2 years) were not shown to be significantly different with Student’s t-test (p = 0.89). There was also a significant difference (p = 0.004) between post-operative time to CT scan between patients with and without evidence of heterotopic ossification on CT scan. Similarly, a Pearson’s chisquare test was performed to compare frequency of ossification between patients with scans less than 180 days post-operatively and scans after 180 days post-operatively. Patients with scans later than 180 days post-operatively were more likely to have evidence of heterotopic ossification (p = 0.007). The fibula osteocutaneous flap is perhaps the most widely used vascularized bone flap for reconstruction of segmental mandibular defects. Once the extirpative part of the surgery is completed and the fibula flap has been elevated, the composite bone and soft tissue graft from the leg is then harvested. A subperiosteal dissection protects the pedicle and preserves the periosteal plexus (see Figure 1). The unused pieces of the fibular bone are then excised and discarded. The proximal periosteum that was dissected off of the discarded fibula is allowed to drape over the peroneal vessels.

Orthotopic Hind-Limb Transplantation in Rats

Composite tissue allotransplantation (CTA) now represents a valid therapeutic option after the loss of a hand, forearm or digits and has become a novel therapeutic entity in reconstructive surgery. However, long term high-dose multi-drug immunosuppressive therapy is required to ensure graft survival, bearing the risk of serious side effects which halters broader application. Further progression in this field may depend on better understanding of basic immunology and ischemia reperfusion injury in composite tissue grafts. To date, orthotopic hind limb transplantation in rats has been the preferred rodent model for reconstructive transplantation (RT), however, it is an extremely demanding procedure that requires extraordinary microsurgical skills for reattachment of vasculature, bones, muscles and nerves. We have introduced the vascular cuff anastomosis technique to this model, providing a rapid and reliable approach to rat hind limb transplantation. This technique simplifies and shortens the surgical procedure and enables surgeons with basic microsurgical experience to successfully perform the operation with high survival and low complication rates. The technique seems to be well suited for immunological as well as ischemia reperfusion injury (IRI) studies.

Free composite tissue graft in treatment of traumatic osteomyelitis combined with bone and skin defect in lower limb

目的 总结不同形式骨皮瓣移植修复下肢创伤后骨髓炎合并骨及软组织缺损的方法和疗效.方法 2001年6月至2006年2月,对38例下肢创伤后骨髓炎合并骨及软组织缺损病例,在创面彻底清创的基础上,根据下肢创面骨缺损的程度、皮肤缺损面积以及复合组织瓣的特点,选择复合骨皮瓣18例、组合骨皮瓣14例、联合(体)骨皮瓣6例移植于受区,一期修复股骨、胫骨、踝关节、跟骨、跖骨等部位骨髓炎并骨及软组织缺损,观察术后皮瓣成活情况、骨折愈合情况及骨髓炎愈合情况.结果 术后随访8～56个月,平均30个月.皮瓣全部成活,伤口Ⅰ期愈合35例,Ⅱ期愈合3例;移植骨全部愈合,愈合时间2～14个月,平均4.6个月;骨髓炎6个月后复发2例,经二次病灶清除后愈合.结论 综合考虑下肢创伤后骨髓炎合并骨及软组织缺损患者整体及患肢情况,对病灶区彻底清创,选择多种形式的复合组织瓣移植,可一期修复下肢骨及软组织缺损,提高机体的抗感染能力,缩短疗程,提高骨髓炎的治愈率。

Monitoring the Changes in Intraparenchymatous Venous Pressure to Ascertain Flap Viability

Disruption of venous outflow can lead to tissue necrosis. Thrombosis of a venous channel at the coaptation site in instances of free tissue transfer could cause death of the transplanted tissues. Although various techniques have been used to monitor the viability of transferred tissues, there has been no technique designed specifically to check the flow within and the patency of the venous channel. The authors have devised an approach with which to monitor the changes in venous pressure in a composite tissue transferred by means of microsurgical technique for bodily reconstruction. The status of the venous system in various composite tissue grafts was monitored at the time of surgery or for 3 days after the completion of surgery by placing a small-caliber catheter in the vein within the transferred tissue. A total of 52 patients participated in the study. The venous pressure noted in grafts with a patent venous channel remained constant within a range between 0 and 35 mmHg. Venous insufficiency was detected in three of the 52 cases, with unmistakable findings of an elevated venous pressure of over 50 mmHg. The technique of measuring the venous pressure by means of an indwelling venous catheter to monitor changes was found to accurately assess the patency of the venous channel and, by inference, the viability of the transferred tissue. No morbidity was associated with the technique.

Why a journal of hand surgery?

Joseph Boyes, in the inaugural editorial of The Journal of Hand Surgery (reprinted on the previous pages), addressed the question “Why a Journal of Hand Surgery?” by noting that published articles concerning the hand were scattered in various textbooks, societal transaction papers, and tissue-oriented periodicals. Although hand surgery had met many of its educational obligations as an established medical discipline, such as sponsoring meetings and courses related to the upper extremity, defining requirements for fellowship training, and publishing a continuously updated bibliography of hand surgery, these activities alone were not sufficient to fulfill hand surgery’s educational mission. A specialty journal devoted exclusively to the upper limb was needed to accomplish its commitment “to improve and develop surgery of the hand.” By all standards, the publication established by Dr Boyes and his founding colleagues has been successful. Nevertheless, the question “Why a Journal of Hand Surgery?” is still pertinent today. It begs, however, a more expanded response, one that focuses not on explaining the need for such a journal, but rather on what we have come to expect of it; that is, what is its purpose and what are its objectives? As envisioned by Dr Boyes, the Journal serves as a principal repository for thoughts and ideas related to surgery of the hand. The 3,804 published articles are the historical record—the archives, so to speak—of the development of our specialty, the authority to which students of hand surgery turn for information. Some proved to be longlasting, some have been modified by ensuing notations and entries, and some became mere footnotes in the ongoing chronicles of hand surgery. Nevertheless, all are essential to defining what hand surgery is and what it will become. Additionally, The Journal of Hand Surgery provides a forum for authors to present new ideas and concepts. From a retrospective view point, ideas that have endured include the development of a classification system to categorize congenital anomalies, the identification of different patterns of carpal bone instability, the importance of tendon mobilization in the rehabilitation of sutured flexor tendons, the use of tubulization to restore continuity to injured peripheral nerves, and the microvascular transfer of composite tissues. Few ideas, however, remain unaltered; most are expanded on, clarified, or even rebutted by subsequent publications. In contrast to textbooks, review articles, and monographs, journal articles represent “current” data and do not enjoy the luxury of being shaped by the reflective perspective of time. No idea is forever and no concept is absolute; all will in time be altered by subsequent information and the presentation of new data. A third principal objective, and perhaps the most important, is to educate the reader. As noted in a 1994 ASSH member survey, The Journal of Hand Surgery is the hand surgeon’s most important instrument in addressing continuing medical education needs, exceeding even that of the annual meeting. At the most basic level,

Effect of cryopreservation on survival of composite tissue grafts.

The problems in cryopreserving complex tissues remain poorly understood. In the present study, the viability of cryopreserved complex tissue, including skin and muscle flaps, and tail, was compared to simple artery and vein grafts in a rat model. Forty-four grafts, including the femoral artery (n = 15), femoral vein (n = 9), gracilis muscle flap (n = 8), groin cutaneous flap (n = 9), and tail (n = 3) were cryopreserved at -196 degrees C for 1 to 2 weeks, and then microvascularly transferred to analogous sites in inbred recipient animals. Three to 60 days post-transplant, all cryopreserved femoral arteries and veins were patent. Host groin cutaneous flaps with cryopreserved vessels grafted into the arterial pedicle survived with no complications However, severe endothelial-cell damage with extensive sloughing in the grafts was demonstrated at 30 min and 1 week following reperfusion, using factor VIII immunologic stain. Reendothelialization was evident at 2 months postoperatively. All cryopreserved composite tissue underwent early pedicle thrombosis The muscle and cutaneous tissue also showed gross and microscopic edema, with extensive red-cell extravasation within 30 min of reperfusion Cryopreservation thus can maintain the functional integrity of simple vessel grafts, but these grafts survive only as a conduit, given the severe endothelial-cell damage The failure of transferred complex cryopreserved tissue may reflect a combination of cellular or architectural damage to the capillary bed from ice formation during the freezing process and from reperfusion injury.

Acute and chronic effects of nicotine on anastomotic patency following ischemia/reperfusion.

The effect of nicotine on anastomotic patency was studied using an isogenic rat-knee transplantation model. Animals were divided into experimental and control groups, with experimental animals exposed to either 40 days of twice-daily nicotine injections (Group 1-chronic exposure) or acute nicotine exposure by graft perfusion (Group 2-acute exposure). Four and 6 hr warm ischemia times were studied. Syngeneic rat knees were transplanted from donor to recipient by microvascular anastomosis of the femoral vessels. There was a statistically significant difference (p < 0.05) in anastomotic patency after 4 hr of ischemia in Group 1 animals exposed to nicotine (33 percent patency) vs. controls (89 percent patency). In addition, there was a statistically significant difference in anastomotic patency after 4 hr of ischemia in Group 2 animals exposed to nicotine (11 percent patency) vs. controls (67 percent patency). No significant differences between controls and Group 1 animals were noted in anastomotic patency after 6 hr of ischemia. Both acute and chronic nicotine exposure reduces anastomotic patency after short intervals of warm ischemia in vascularized composite tissue grafts. This detrimental effect is lost when the ischemic interval is prolonged to periods with poor anastomotic patency rates related to the ischemia/reperfusion itself.

Neutrophil lipoxygenase activation and leukosequestration in postischemic myocutaneous flaps: role of LTB4.

Reperfusion of ischemic tissues leads to eicosanoid- and polymorphonuclear leukocyte (PMN)-dependent injury. The present experiments were undertaken to examine the effect of myocutaneous flap ischemia-reperfusion on neutrophil 5-lipoxygenase activity and to define the role of leukotriene B4 (LTB4) in postischemic PMN infiltration into such composite tissue grafts. Anesthetized Yorkshire pigs underwent 6 h of rectus abdominis myocutaneous flap ischemia or sham ischemia, and LTB4 generation was measured in calcium ionophore-stimulated neutrophils isolated from the circulation. At 30 min of reperfusion, neutrophil generation of LTB4 increased from a baseline value of 31.0 +/- 6.8 to 98.5 +/- 5.1 ng/5 x 10(6) PMN (P < 0.01) and was significantly greater than those neutrophils isolated from animals subjected to sham ischemia and reperfusion (54.3 +/- 4.1 ng/5 x 10(6) PMN; P < 0.01). Pretreatment of animals with the LTB4-receptor antagonist, SC-41930 (n = 5), significantly attenuated reperfusion-associated 5-lipoxygenase activation (60.3 +/- 11.6 ng LTB4/5 x 10(6) PMN; P < 0.01), suggesting the presence of a positive feedback mechanism for eicosanoid biosynthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Replantation of the radial side of the hand in the rhesus monkey: anatomical and functional aspects. A preliminary study to composite tissue allografting.

Before human hand transplantation can even be considered, an appropriate research model must be studied in a non-human primate. The first ray of the hand, augmented with a radial forearm flap, was chosen as a functional composite tissue graft. Four technically successful replantation of the radial unit have been carried out. One monkey died on the first post-operative day due to cardiac arrythmia. Normal wound healing occurred in the other three animals. In three monkeys, functional sensory and motor recovery was almost complete. The monkeys were able to pick up small particles of food with the index finger and thumb. It is suggested that this model could be used for allogeneic composite tissue transplantation in a non-human primate.

Nuclear Medicine in Evaluation of the Hand and Wrist

Radionuclide evaluation of the hand and wrist is best performed with three-phase scintigraphy. This recent modification of the conventional bone scan includes a radionuclide angiogram to assess blood flow, as well as images that depict soft-tissue inflammation and areas of abnormal bone turnover. The clinical applications of three-phase scintigraphy include evaluation of patients with suspected vascular disorders, hand masses, infections, pain of uncertain etiology, and viability of composite tissue grafts.

Management of infected fractures of the tibia with associated soft tissue loss: experience with external fixation, bone grafting and soft tissue reconstruction using pedicle muscle flaps or microvascular composite tissue grafts

The aim of this study was to assess the results of treatment given by a team of orthopaedic and plastic surgeons in a series of infected unhealed fractures of the tibia associated with loss of adjacent soft tissues. Twenty-five lower leg fractures, treated during a 10 year period, entered the study and were grouped according to the principles of treatment followed. In the earlier Group A (nine patients), the osteosynthesis implants were retained or changed to more stable internal fixation devices, the soft tissue defects were closed by conventional muscle or musculocutaneous flaps and bone grafting procedures were performed late in the treatment scheme. In the later Group B (16 patients) the implants were removed and the fracture stabilised by external fixation; the defects were covered with pedicle muscle flaps or with microvascular composite tissue grafts and cancellous bone grafting was performed at the same operation. Twenty-three fractures healed. One fracture developed non-union and in one patient infection necessitated below-knee amputation. The time of union after surgical reconstruction was significantly shorter in Group B (24 ± 3 weeks) than in Group A (47 ± 11 weeks). The results suggested that: (1) in severe infected fractures of the tibia surgical implants used previously for fracture treatment should be removed and replaced with an external frame using firm axial compression, (2) microvascular composite grafts seem to improve greatly the rate of healing, (3) early bone grafting should be included in the reconstruction and (4) late infections can be largely avoided even after extensive one-stage reconstructive procedures.

Patency rates in microvascular prostheses: An experimental study

The perfection of techniques of micrdvascular anastomosis has now made possible the successful replantation of amputated fingers (O’Brien et al., 1973 a,b.) and free flap transfers of composite tissue grafts (Daniel and Williams, 1973; Krizek et al., 1965). The success rate in microvascular vessel repair is obviously greater if the small vessel has been cleanly cut than if a segment of the vessel is missing and some form of replacement is required. In these cases, two options remain open to the surgeon: shortening of the injured organ to allow vessel approximation or bridging the vasculpr defect with a vein graft. The former may produce a result that is cosmetically and functionally unacceptable: the latter decreases the success rate because in practice it may be difficult and sometimes impossible to find a suitable vein graft to match the length and diameter of the defect. The search may be time consuming and so too may the performance of the proximal and distal anastomosis. Under these circumstances the value of a readily available microvascular prosthesis would be considerable. provided that the patency of the prosthesis could be assured. This study was designed to investigate the long-term patency of synthetic tubular micrografts inserted into the rat abdominal aorta. Two different synthetic materials were tested: silicone and expanded polytetrafluooethylene (PTFE).

Homologous composite tissue grafts of the digital flexor mechanism in human beings.

Department of Surgery, University of North Carolina School of Medicine, and the North Carolina Memorial Hospital, Chapel Hill, North Carolina.