Biopolymer gel matrix as acellular scaffold for enhanced dermal tissue regeneration

Biological grafts have drawbacks such as donor scarcity, disease transmission, tissue infection, while the scaffolds of either collagen or chitosan fabrics fail to become part of the tissue at the wound site, though they favor the formation of connective tissue matrix. This study developed a novel composite consisting of the combination of atelocollagen and chitosan in order to provide a biodegradable molecular matrix in gel form as a biomimetic surface for cell attachment, to promote the wound healing in excision wounds. We found that the topical application of biopolymer composite on the wound promoted cell proliferation, migration and collagen deposition overtime. The enhanced cellular activity in the collagen-chitosan treated wound tissue was also assed by increased levels of Platelet derived growth factor (PDGF) and Nerve growth factor (NGF) associated with elevated levels of antioxidants and decreased level of lipid peroxidation. The acellular matrix-like topical application material is designed to guide the eventual re-establishment of an anatomically normal skin. The results of this study demonstrate the feasibility of multi-cell regeneration on a molecular system that mimics tissue engineering in vivo.     

A 10-year experience in nasal reconstruction with the three-stage forehead flap

Because of its ideal color and texture, forehead skin is acknowledged as the best donor site with which to resurface the nose. However, all forehead flaps, regardless of their vascular pedicles, are thicker than normal nasal skin. Stiff and flat, they do not easily mold from a two-dimensional to a three-dimensional shape. Traditionally, the forehead is transferred in two stages. At the first stage, frontalis muscle and subcutaneous tissue are excised distally and the partially thinned flap is inset into the recipient site. At a second stage, 3 weeks later, the pedicle is divided. However, such soft-tissue "thinning" is limited, incomplete, and piecemeal. Flap necrosis and contour irregularities are especially common in smokers and in major nasal reconstructions. To overcome these problems, the technique of forehead flap transfer was modified. An extra operation was added between transfer and division.At the first stage, a full-thickness forehead flap is elevated with all its layers and is transposed without thinning except for the columellar inset. Primary cartilage grafts are placed if vascularized intranasal lining is present or restored. Importantly, at the first stage, skin grafts or a folded forehead flap can be used effectively for lining. A full-thickness skin graft will reliably survive when placed on a highly vascular bed. A full-thickness forehead flap can be folded to replace missing cover skin, with a distal extension, in continuity, to supply lining. At the second stage, 3 weeks later during an intermediate operation, the full-thickness forehead flap, now healed to its recipient bed, is physiologically delayed. Forehead skin with 3 to 4 mm of subcutaneous fat (nasal skin thickness) is elevated in the unscarred subcutaneous plane over the entire nasal inset, except for the columella. Skin grafts or folded flaps integrate into adjacent normal lining and can be completely separated from the overlying cover from which they were initially vascularized. If used, a folded forehead flap is incised free along the rim, completely separating the proximal cover flap from the distal lining extension. The underlying subcutaneous tissue, frontalis muscle, and any previously positioned cartilage grafts are now widely exposed, and excess soft tissue can be excised to carve an ideal subunit, rigid subsurface architecture. Previous primary cartilage grafts can be repositioned, sculpted, or augmented, if required. Delayed primary cartilage grafts can be placed to support lining created from a skin graft or a folded flap. The forehead cover skin (thin, supple, and conforming) is then replaced on the underlying rigid, recontoured, three-dimensional recipient bed. The pedicle is not transected. At a third stage, 3 weeks later (6 weeks after the initial transfer), the pedicle is divided.Over 10 years in 90 nasal reconstructions for partial and full-thickness defects, the three-stage forehead flap technique with an intermediate operation was used with primary and delayed primary grafts, and with intranasal lining flaps (n = 15), skin grafts (n = 11), folded forehead flaps (n = 3), turnover flaps (n = 5), prefabricated flaps (n = 4), and free flaps for lining (n = 2). Necrosis of the forehead flap did not occur. Late revisions were not required or were minor in partial defects. In full-thickness defects, a major revision and more than two minor revisions were performed in less than 5 percent of patients. Overall, the aesthetic results approached normal.The planned three-stage forehead flap technique of nasal repair with an intermediate operation (1) transfers subtle, conforming forehead skin of ideal thinness for cover, with little risk of necrosis; (2) uses primary and delayed primary grafts and permits modification of initial cartilage grafts to correct failures of design, malposition, or scar contraction before flap division; (3) creates an ideal, rigid subsurface framework of hard and soft tissue that is reflected through overlying skin and blends well into adjacent recipient tissues; (4) expands the application of lining techniques to include the use of skin grafts for lining at the first stage, or as a "salvage procedure" during the second stage, and also permits the aesthetic use of folded forehead flaps for lining; (5) ensures maximal blood supply and vascular safety to all nasal layers; (6) provides the surgeon with options to salvage reconstructive catastrophes; (7) improves the aesthetic result while decreasing the number and difficulty of revision operations and overall time for repair; and (8) emphasizes the interdependence of anatomy (cover, lining, and support) and provides insight into the nature of wound injury and repair in nasal reconstruction.     

Human polymer-based cartilage grafts for the regeneration of articular cartilage defects

The use of autologous chondrocyte implantation (ACI) and its further development combining autologous chondrocytes with bioresorbable matrices may represent a promising new technology for cartilage regeneration in orthopaedic research. Aim of our study was to evaluate the applicability of a resorbable three-dimensional polymer of pure polyglycolic acid (PGA) for the use in human cartilage tissue engineering under autologous conditions. Adult human chondrocytes were expanded in vitro using human serum and were rearranged three-dimensionally in human fibrin and PGA. The capacity of dedifferentiated chondrocytes to re-differentiate was evaluated after two weeks of tissue culture in vitro and after subcutaneous transplantation into nude mice by propidium iodide/fluorescein diacetate (PI/FDA) staining, scanning electron microscopy (SEM), gene expression analysis of typical chondrocyte marker genes and histological staining of proteoglycans and type II collagen. PI/FDA staining and SEM documented that vital human chondrocytes are evenly distributed within the polymer-based cartilage tissue engineering graft. The induction of the typical chondrocyte marker genes including cartilage oligomeric matrix protein (COMP) and cartilage link protein after two weeks of tissue culture indicates the initiation of chondrocyte re-differentiation by three-dimensional assembly in fibrin and PGA. Histological analysis of human cartilage tissue engineering grafts after 6 weeks of subcutaneous transplantation demonstrates the development of the graft towards hyaline cartilage with formation of a cartilaginous matrix comprising type II collagen and proteoglycan. These results suggest that human polymer-based cartilage tissue engineering grafts made of human chondrocytes, human fibrin and PGA are clinically suited for the regeneration of articular cartilage defects.     

REPAIR OF INJURIES TO SOFT TISSUES OF FINGERS—Primary and Secondary Reconstruction

Preservation of maximum function and appearance of the finger can best be attained by wide excision of crushed or traumatized tissue and closure of defects by primary split thickness skin grafts. Primary pedicle flaps are rarely indicated and should be reserved for cover of denuded cortical bone or joint surfaces. In only 1 per cent of fresh injuries were primary pedicle flaps used. Finger length, nail bed and root, bone and tendon can be adequately preserved with minimal morbidity by split thickness skin grafts. Restoration of contour if necessary is best done secondarily, utilizing thenar or hypothenar flaps. These flaps are particularly indicated in the reconstruction of finger tips.     

Vascularized rib for facial reconstruction

The reconstruction of maxillectomy defects is a complex problem encountered in plastic surgery. Defects can range in size and complexity from small defects requiring only soft tissue to complete maxillectomies requiring large tissue bulk, bone, and one or more skin paddles. The most difficult defects involve the skull base and orbit. The reconstructive surgeon is faced with the challenge of isolating the nasopharynx from the dura and globe while simultaneously restoring the bony framework of the maxilla and orbit to support the soft tissue of the cheek. The authors present a series of six reconstructions using a rectus abdominis muscle flap with associated vascularized rib for reconstruction of complex maxillectomy defects. This flap provides large soft-tissue bulk as well as bony support and a long vascular pedicle. A skin island can be taken with the flap, and the donor-site morbidity is comparable to that seen with a vertical rectus abdominis myocutaneous flap. Six flaps were used in five patients over a 20-month period. All patients had stable support of the orbit at follow-up with adequate soft-tissue coverage, and there were no incidences of visual changes.     

胸三角皮瓣并自体脂肪移植修复颌面部大面积缺损畸形

目的：探讨颌面部皮肤软组织大面积缺损凹陷的理想修复方法。方法：本组6例均为爆炸伤后颌面部皮肤软组织缺损及严重凹陷畸形,采用胸三角皮肤扩张形成带蒂皮瓣修复上述皮肤缺损及自体脂肪移植纠正残存凹陷畸形。手术分五步进行：1．胸三角深筋膜浅层埋植500mL-800mL皮肤扩张器并注水扩张3个月。2井艮据面颈部预计皮肤缺损大小及形状作皮瓣预制并面部局部皮瓣纠正器官移位。3．带蒂皮瓣转移修复颌面部缺损。4．蒂部延迟及断蒂微整形。5．自体脂肪移植。结果：所有皮瓣成活良好,皮瓣色质接近面颈部周围正常皮肤,缺损畸形修复,外观形态好,供区直接缝合无需植皮,取得了较好的面部改观效果。结论：对于面部大面积皮肤软组织缺损,合并面部凹陷、面部器官缺损及移位,采取胸三角扩张延迟预制皮瓣并自体脂肪移植修复可取得良好的整复效果,为颌面部战创伤畸形提供了理想的修复方法。     

The role of serum imbibition for skin grafts

Numerous studies of grafted skin suggest that full-thickness skin grafts are nourished by exudate from the recipient bed called a serum imbibition. However, whether serum imbibition by itself is sufficient for nourishment of skin grafts has not been shown definitely and directly. To clarify the role of serum imbibition, we performed a comparative study between 20 skin grafts and 20 musculocutaneous flaps. The nourishment of the cell in the skin graft is by serum imbibition. That in musculocutaneous flaps is mainly derived from blood supply. We evaluated the nourishment by means of the unique characteristics of the cell cycle. Once cells are put into a synthetic phase, they cannot reverse or stop the progress of the cell cycle. To take advantage of this characteristic of the cell cycle, prewounding methods (40 flaps were lifted once and put back to the original sites prior to the evaluation) were intended for the cells in pre-elevated skin to turn into a proliferating phase. Cells were examined by antibody against proliferating cell nuclear antigen immunohistologically, to determine whether they had turned into the proliferating phase or not. After 3 days, all flaps were reelevated; half (20 flaps) had their muscle layer and the neurovascular bundle removed to make a full-thickness skin graft. The rest (20 flaps) were only lifted. They were sutured back to the original sites. Ten skin grafts and musculocutaneous flaps each were harvested at 3 hours (1st day) and at 11 days (11th day) after the second operation. Bromodeoxyuridine, which is a thymidine analog and is taken into the cells in the synthetic phase, was introduced intraperitoneally 2 hours before the harvest. All flaps and grafts were evaluated histologically and immunohistologically. Proliferating cell nuclear antigen analysis showed that the prewounding method induced the cells of skin grafts and musculocutaneous flaps to proliferate before the implantation. Regarding the bromodeoxyuridine uptake, no significant differences could be seen between skin grafts and musculocutaneous flaps irrespective of their different nourishment. No structural changes, such as degenerative or necrotic, could be seen at the hair follicle and other glands even at the 11th day. Almost all of the layers of skin grafts survived as long as they were checked by light microscopy (hematoxylin and eosin stain). No differences could be seen between musculocutaneous flaps and skin grafts or between the 1st and 11th days in this study. We concluded that serum imbibition is sufficient for nourishment of skin grafts, just as blood supply is sufficient for nourishment of musculocutaneous flaps.     

Review collagen‐based biomaterials for wound healing

With its wide distribution in soft and hard connective tissues, collagen is the most abundant of animal proteins. In vitro, natural collagen can be formed into highly organized, three‐dimensional scaffolds that are intrinsically biocompatible, biodegradable, nontoxic upon exogenous application, and endowed with high tensile strength. These attributes make collagen the material of choice for wound healing and tissue engineering applications. In this article, we review the structure and molecular interactions of collagen in vivo; the recent use of natural collagen in sponges, injectables, films and membranes, dressings, and skin grafts; and the on‐going development of synthetic collagen mimetic peptides as pylons to anchor cytoactive agents in wound beds. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 821–833, 2014.     

Proteomic analysis of Col11a1-associated protein complexes

Cartilage plays an essential role during skeletal development within the growth plate and in articular joint function. Interactions between the collagen fibrils and other extracellular matrix molecules maintain structural integrity of cartilage, orchestrate complex dynamic events during embryonic development, and help to regulate fibrillogenesis. To increase our understanding of these events, affinity chromatography and liquid chromatography/tandem mass spectrometry were used to identify proteins that interact with the collagen fibril surface via the amino terminal domain of collagen α1(XI) a protein domain that is displayed at the surface of heterotypic collagen fibrils of cartilage. Proteins extracted from fetal bovine cartilage using homogenization in high ionic strength buffer were selected based on affinity for the amino terminal noncollagenous domain of collagen α1(XI). MS was used to determine the amino acid sequence of tryptic fragments for protein identification. Extracellular matrix molecules and cellular proteins that were identified as interacting with the amino terminal domain of collagen α1(XI) directly or indirectly, included proteoglycans, collagens, and matricellular molecules, some of which also play a role in fibrillogenesis, while others are known to function in the maintenance of tissue integrity. Characterization of these molecular interactions will provide a more thorough understanding of how the extracellular matrix molecules of cartilage interact and what role collagen XI plays in the process of fibrillogenesis and maintenance of tissue integrity. Such information will aid tissue engineering and cartilage regeneration efforts to treat cartilage tissue damage and degeneration.     

Free anterolateral thigh adipofascial perforator flap

The anterolateral thigh adipofascial flap is a vascularized flap prepared from the adipofascial layer of the anterolateral thigh region. It is a perforator flap based on septocutaneous or musculocutaneous perforators of the lateral circumflex femoral system. With methods similar to those used for the free anterolateral thigh flap, only the deep fascia of the anterolateral thigh and a 2-mm-thick to 3-mm-thick layer of subcutaneous fatty tissue above the fascia were harvested. In 11 cases, this flap (length, 5 to 11 cm; width, 4 to 8 cm) was used for successful reconstruction of extremity defects. Split-thickness skin grafts were used to immediately resurface the adipofascial flaps for eight patients, and delayed skin grafting was performed for the other three patients. The advantage of the anterolateral thigh adipofascial flap is its ability to provide vascularized, thin, pliable, gliding coverage. In addition, the donor-site defect can be closed directly. Other advantages of this flap, such as safe elevation, a long wide vascular pedicle, a large flap territory, and flow-through properties that allow simultaneous reconstruction of major-vessel and soft-tissue defects, are the same as for the conventional anterolateral thigh flap. The main disadvantage of this procedure is the need for a skin graft, with the possible complications of subsequent skin graft loss or hyperpigmentation.     

Scalping injuries: new technique for stabilization of flaps to the skull

Extensive scalping injuries offer a unique challenge for tissue coverage because of the wide expanse of bone and lack of deep soft tissue or significant perforating vessels. For smaller injuries, pedicle flaps offer ideal coverage. Larger defects can be covered by omental flaps. Coverage with a free muscle flap followed by split-thickness skin grafting offers optimal long-term coverage. Two new techniques are introduced. The wire-button technique offers stabilization, and the halo frame provides good support and protection for a new free-flap graft and may increase the success rate of flaps in patients with scalping injuries.     

A Silk Fibroin/Collagen Nerve Scaffold Seeded with a Co-Culture of Schwann Cells and Adipose-Derived Stem Cells for Sciatic Nerve Regeneration

As a promising alternative to autologous nerve grafts, tissue-engineered nerve grafts have been extensively studied as a way to bridge peripheral nerve defects and guide nerve regeneration. The main difference between autogenous nerve grafts and tissue-engineered nerve grafts is the regenerative microenvironment formed by the grafts. If an appropriate regenerative microenvironment is provided, the repair of a peripheral nerve is feasible. In this study, to mimic the body’s natural regenerative microenvironment closely, we co-cultured Schwann cells (SCs) and adipose-derived stem cells (ADSCs) as seed cells and introduced them into a silk fibroin (SF)/collagen scaffold to construct a tissue-engineered nerve conduit (TENC). Twelve weeks after the three different grafts (plain SF/collagen scaffold, TENC, and autograft) were transplanted to bridge 1-cm long sciatic nerve defects in rats, a series of electrophysiological examinations and morphological analyses were performed to evaluate the effect of the tissue-engineered nerve grafts on peripheral nerve regeneration. The regenerative outcomes showed that the effect of treatment with TENCs was similar to that with autologous nerve grafts but superior to that with plain SF/collagen scaffolds. Meanwhile, no experimental animals had inflammation around the grafts. Based on this evidence, our findings suggest that the TENC we developed could improve the regenerative microenvironment and accelerate nerve regeneration compared to plain SF/collagen and may serve as a promising strategy for peripheral nerve repair.     

Leave the fat, skip the bolster: thinking outside the box in lower third nasal reconstruction

Defects of the lower third of the nose often present especially challenging reconstructive dilemmas. The surrounding skin to match is often thick, sebaceous, and sun damaged, none of which characterizes the historically ideal periauricular donor skin for grafting. The surrounding nasal skin is quite stiff, precluding very small local flaps. To avoid the "misplaced patch" appearance of most classic full-thickness grafts to this area or the depressed scar of an elliptical excision, many surgeons turn to larger local or regional flaps. These provide not only skin color and texture match but also the necessary several millimeters of subcutaneous fat necessary for proper tip aesthetics. Many defects of the lower third are small, making many surgeons reluctant to employ these larger flaps with their long scars and potential to twist or distort delicate tip or ala anatomy. The author has sought a means to transport skin and subcutaneous fat for lower third nasal defects outside of flaps. On the basis of the superiority of nasolabial fold scars and a vast positive experience in the literature utilizing skin and fat composite grafts with no bolsters, the author applied these techniques to 33 lower third nasal defects in 29 patients. Of 33 grafts varying in size from 4 mm circular to 17 mm x 16 mm and retaining 1 to 5 mm of fat, no grafts were lost. Four grafts developed a 30 percent area or less of central necrosis resulting in localized depression. Three of these four grafts were in active smokers and the fourth graft was in a former smoker. Aside from these four grafts and one with considerable excess fat early in the series, contour was good to excellent. Hypopigmentation is still common but improves with time. Easily performed composite grafts effectively carry the necessary fat for aesthetic reconstruction and do not risk long scars on the nose and twisting of the tip and ala that can result from flaps. Revisions are infrequent and extremely simple when indicated.     

Wound healing effect of collagen-hyaluronic acid implanted in partially injured anterior cruciate ligament of dog

The purpose of this study was to evaluate the cell compatibility of collagen-hyaluronan (HA) substrate in vitro by assessing ACL cell cultures. Additionally, the use of collagen-HA substrate as a dressing material for partial ACL defects as well as its effect on collagen synthesis and angiogenesis were evaluated in vivo. The initial attachment and proliferation of dog ACL cells on silk matrix covered with collagen-HA substrate (SMCH) was greater than that observed on silk matrix alone. Silk matrix and SMCHs were implanted as dressing materials into partial ACL defects located at the knees of dogs, and they were harvested six weeks after implantation. A histological evaluation of the collagen-HA substrates revealed the presence of monocytes and the absence of giant cells in all cases. MT staining of the SMCH-grafted group showed a higher level of granulation tissue formation consisting of fibroblasts and collagen fibers compared to the silk matrix-grafted group. In addition, CD31 staining revealed that the SMCH-grafted area showed more blood vessel formation than the silk matrix-grafted area. These results suggest that the collagen-HA substrate was cell-compatible in vitro and enhanced collagen synthesis and new blood vessel formation in vivo.     

带腓肠腱膜的腓肠神经营养皮瓣修复KuwadeⅣ型跟腱缺损

目的:回顾性分析带腓肠肌腱膜的腓肠神经营养皮瓣修复KuwadeⅣ型跟腱缺损的临床病例,探讨其手术注意事项及治疗经验。方法:总结2008年5月-2013年8月收治的KuwadeⅣ型跟腱缺损19例,应用带腓肠肌腱膜的腓肠神经营养皮瓣进行一期修复。7例为新鲜损伤,12例为陈旧性缺损。19例跟腱缺损均伴有皮肤及软组织坏死,皮肤缺损范围为4.0 cm×6.0 cm-6.0cm×12.0 cm,跟腱缺损长度为5-9 cm,术中皮瓣切取范围为6.0 cm×5.5 cm-12.0 cm×8.0cm,腓肠腱膜切取范围5.5 cm×6.0cm-10.0 cm×6.0 cm;供区游离植皮修复。客观性评价指标包括关节跖屈、背伸动度及形态学,主观性评价采用AOFAS评分。结果:术后17例跟腱功能重建良好,2例感染控制不良,跟腱移植体部分坏死。皮瓣完全成活13例,创面Ⅰ期愈合。2例术后6天皮瓣远端表皮坏死,经换药后愈合。2例术后10天皮瓣远端部分坏死,经局部皮瓣移位修复愈合,2例感染控制不良者,皮瓣未愈合,移植跟腱部分坏死,经再次清创后,行阔筋膜条修复术,局部皮瓣移位修复。术后19例均获随访,随访时间6~24个月,平均18个月。术后皮瓣略臃肿,但不影响穿鞋,行走功能恢复良好,术后1年AOFAS评分平均80.31分。结论:带腓肠肌腱膜的腓肠神经营养皮瓣用于治疗KuwadeⅣ型跟腱缺损,可以同时修复皮肤及跟腱缺损,是一种较为理想的一期修复方法。     

The use of free revascularized grafts in the amelioration of hemifacial atrophy

Nine female and three male patients, 5 to 47 years old, were treated by free revascularized grafts for Romberg's disease. Greater omentum was transferred in nine, de-epithelialized skin flaps in three. Follow-up ranges from several months to 7 years. Microvascular failures or donor site complications did not occur. To further trim transferred tissue, overcome gravitational sag, or both, all but one patient required a secondary procedure. The only facial complication included partial loss of the transferred omentum and spotty necrosis of the overlying skin. The choice of omentum or de-epithelialized skin and subcutaneous fat is dictated by the extent of the facial defect. Generalized defects are corrected with omentum and localized segmental defects with de-epithelialized flaps. Because of observed late complications, including chronic inflammation, induration, and sinus tracts, we no longer recommend medical-grade liquid silicone as a therapeutic option in the palliation of Romberg's disease.     

The distally pedicled peroneus brevis muscle flap: a new flap for the lower leg

Defects of the skin and soft tissue in the region of the lateral malleolus of the ankle and the Achilles tendon, resulting in exposed bone, tendons, or osteosynthetic material, cannot be covered with free skin transplants. Local or free flaps must be employed. The authors present the construction of a peroneus brevis muscle flap with a distal pedicle as a useful alternative. Between 1993 and 1999, distal pedicled peroneus brevis muscle flaps were used in 19 patients with various types of defects. During construction of the flap, both the long peroneal muscle and the peroneal artery remained intact. In the region of the distal third of the fibula, consistently arranged branches run from the artery into the muscle, and these form the distal pedicle. The proximal portion of the muscle can be transposed distally and easily extends to the tip of the fibula and the attachment of the Achilles tendon to the calcaneus. Primary healing occurred in 16 patients undergoing flap construction. Donor-site morbidity was mostly limited to the donor-site scar. The distally pedicled peroneus brevis muscle flap is a reliable means for covering defects in the lower leg. This form of muscle flap has not yet been described in the known literature. In the authors' opinion, this flap constitutes a logical and valuable extension of local flap procedures for plastic surgery in the distal leg region.     

Biochemical and biophysical aspects of collagen nanostructure in the extracellular matrix

ECM is composed of different collagenous and non-collagenous proteins. Collagen nanofibers play a dominant role in maintaining the biological and structural integrity of various tissues and organs, including bone, skin, tendon, blood vessels, and cartilage. Artificial collagen nanofibers are increasingly significant in numerous tissue engineering applications and seem to be ideal scaffolds for cell growth and proliferation. The modern tissue engineering task is to develop three-dimensional scaffolds of appropriate biological and biomechanical properties, at the same time mimicking the natural extracellular matrix and promoting tissue regeneration. Furthermore, it should be biodegradable, bioresorbable and non-inflammatory, should provide sufficient nutrient supply and have appropriate viscoelasticity and strength. Attributed to collagen features mentioned above, collagen fibers represent an obvious appropriate material for tissue engineering scaffolds. The aim of this minireview is, besides encapsulation of the basic biochemical and biophysical properties of collagen, to summarize the most promising modern methods and technologies for production of collagen nanofibers and scaffolds for artificial tissue development.     

Influence of human skin injury on regeneration of sensory neurons

The regeneration of sensory nerve fibres is regulated by trophic factors released from their target tissue, particularly the basal epidermis, and matrix molecules. Means to modulate this response may be useful for the treatment of neuromas and painful hypertrophic scars and of sensory deficits in skin grafts and flaps. We have developed an in vitro model of sensory neuron regeneration on human skin in order to study the mechanisms of sensory dysfunction in pathological conditions. Adult rat sensory neurons were co-cultured with unfixed cryosections of normal or injured (crushed) human skin for 72 h. Neurons were immunostained for growth-associated protein-43 and the neurite lengths of neuronal cell bodies situated in various skin regions were measured. Two-way analysis of variance was performed. Neurites of sensory cell bodies on epidermis of normal skin were the shortest, with a mean +/- SEM of 75+/-10 micrometer, whereas those of cells on the dermo-epidermal junction were the longest, with a mean +/- SEM of 231+/-18 micrometer. Neurons on the dermo-epidermal junction of injured skin had significantly longer neurites than those on the same region of normal skin (mean +/- SEM = 289+/-21 micrometer). Regeneration of sensory neurons may be influenced by extracellular matrix molecules, matrix-binding growth factors and trophic factors. Altered substrate or trophic factors in injured skin may explain the increase of neurite lengths. This in vitro model may be useful for studying the molecular mechanisms of sensory recovery and the development of neuropathic pain following peripheral nerve injury.     

The vastus lateralis myocutaneous flap

Four case reports of decubiti treated with vastus lateralis myocutaneous flaps are presented. The operative technique is described in detail. This method, closing the donor site primarily over Hemovac drains and eliminating the use of skin grafts, can be used to cover defects in a variety of locations.