Chinese Journal of Plastic Surgery, Vol. 18, No. 5, Sep. 2002
Research and application of allogeneic acellular dermal matrix
Huo Menghua, Qi Keming, Golden Well
Acellular dermal matrix (ADM) is a dermal substitute obtained by special treatment of allogeneic skin to remove its cellular components. Developed by Livesey [1] and produced by Lifecell under the trade name AlloDerm, it has been approved by the US FDA for clinical use, and has been widely used and developed in the field of burns and plastic surgery in recent years.
1. Preparation method of acellular dermal matrix
The preparation of ADM consists of three basic steps: epidermal depletion, dermal cell removal and freeze-drying, and there are two methods. First, the skin of the cadaver was treated with hypertonic saline and sodium 12-alkyl sulfate (SDS) to form NaCl-SDS ADM [1,2]; Second, Dispase-Triton ADM is formed after treatment with DispaseII. and then with Triton X-100[3]. The two treatment methods were different, and the ADM obtained was slightly different, in which the cellular components were removed, the basic structure of the matrix was intact, and elastin, keratin sulfate, laminin, and type III and IV collagen were lost, but still retained in sufficient quantities; In contrast, the Dispase-Triton ADM contains fewer antigenic components, while the NaCl-SDS ADM contains more collagen type IV, fibrobindin, conjugectin, elastin, and HLA-DR [4].
2. Biological characteristics
The immune response to the allogeneic skin mainly acts on the cell components such as epidermal cells, fibroblasts and endothelial cells in the dermis, while the non-cellular components of the dermis extracellular matrix proteins and collagen (i.e., ADM) are relatively inactive and can be permanently present in the host body. As an allogeneic dermis, ADM has completely eliminated cellular components and type I and II cytocompatible antigens, has low immune activity, and does not induce a specific cellular immune response (i.e., rejection) to allogeneic tissue transplantation, nor does it induce a non-specific foreign body response [5]. The basement membrane complex is retained in ADM, forming two sides, the basement membrane and the dermis, which are conducive to the rapid vascularization of ADM, and the basement membrane surface can provide a natural plane for the migration and colonization of epithelial cells, which is conducive to the epithelialization of ADM [2,6].
The amount of dermal composition is an important factor in the elasticity and appearance of the wound after healing, and the amount of scarring and the degree of contracture are inversely proportional to the amount of dermis in the grafted skin piece [7]. When dermal content is insufficient, fibroblasts can only synthesize immature substrates, which are remodeled to become scar tissue [8]. ADM, as a dermal substitute, provides a sufficient amount of dermal tissue to the wound to reduce scarring and contracture. Regularly arranged collagen bundles and elastic fibers are structures necessary for the normal functioning of the dermis, and granulation tissue and scar tissue are characterized by dysplasia and elastic fiber deficiency [9]. The structure of the extracellular matrix in ADM is intact, providing a good scaffold for the regeneration of tissue cells, and extracellular matrix proteins can promote the attachment and proliferation of epidermal cells [10]. Fibroblasts transferred into ADM from the base of the wound still have the ability to produce a mature matrix[2]. ADM was implanted subcutaneously for 2 weeks, with mild lympho-histiocyte infiltration and neovascularization, very mild inflammation, and inflammation subsided at 4 weeks, after which there were no obvious histological changes and no tissue rejection. ADM transplantation is partially vascularized at 1 week of open wound transplantation, extensive vascularization occurs at 2 weeks, and then does not increase, epithelialization appears at the ADM margin at 3 weeks, and epithelium covers the entire wound at 4 weeks [3]. Fibroblast migration and vascularization can occur one month after xenogeneic ADM transplantation [11].
ADM has good flexibility, is easy to trim, can be cut, overlapped, rolled into rolls, and can also be made into micronized form for intradermal or subcutaneous injection, where fibroblast migration and collagen deposition can be seen. ADM has low metabolic requirements [12]. There are different degrees of absorption after vascularization of ADM, and the reports vary from no absorption [13,14] to obvious absorption, mostly between 15%~20% [2,3,13-16], which occurs within 4~6 weeks after surgery. ADM absorption may be related to poor blood vascularization in ADM-affected tissues, ADM exposure, dehydration, dryness, mobility, and mild chronic infection.
The cell-free nature of ADM greatly reduces the likelihood of inflammation, and after ADM transplantation, the body treats it as autologous tissue and gradually reshapes it into a tissue similar to autologous tissue. Neonatal fibroblasts can synthesize autologous collagen 5~8 weeks after ADM transplantation[2]. When collagen deposition and absorption reach a dynamic equilibrium, the implant acquires a stable volume. The factors influencing this homeostasis include the vascularization process, local mobility, stress, inflammation and tissue intrinsic factors in the affected area, which require further research.
3. Clinical and experimental application research
1. Application of burn wounds: ADM, as a dermal substitute, can provide sufficient dermis for burn wounds, thereby significantly reducing scarring and scar contracture. The modalities of transplantation vary from one to the next, but ADM and autologous ultrathin skin slice can be transplanted with primary or secondary surgery [2,3]. Epidermal cells [17] and oral mucosal epithelial cells [18] can be cultured directly on ADM and then transplanted into the wound or used as oral mucosal substitutes. ADM is implanted under the skin, and after two weeks of vascularization, it is lifted and rotated to form a pre-constructed dermal flap, on which a cultured autologous epidermal cell membrane is transplanted to repair adjacent skin defects [19].
2. Repair of diaphragmatic defects: full-thickness excision of the central part of the left diaphragm of SD chicks, and then repaired with ADM, the results of ADM survival are good, can grow by random growth, and there is no local bulge, which is an ideal diaphragm repair material, especially suitable for the repair of diaphragmatic defects in children [20].
3. Repair of dural defects: Repair dural defects by facing the basement membrane surface of ADM toward the brain tissue and continuous suturing with the edge of the dural defect can effectively prevent CSF leakage and the resulting secondary infection, without brain tissue adhesion [14].
Barret [21] reported a 6-week-old child with type IV skull burn who was completely removed from the necrotic bone, dura mater, and superficial brain tissue, and then repaired the defect with ADM and ultrathin skin grafting. Chaplin [11] also confirmed through animal experiments that xenoADM (XenoDerm) is suitable for dural defect repair as well as allogeneic ADM (AlloDerm).
4. Lip augmentation: In 1993, Cuerrissi used a dermal flap to perform lip rejuvenation surgery, in which a strip of skin above the red edge of the lip was reepidermized to make a dermal flap, and then a capsular pouch was peeled off under the skin on 1/3 of the upper lip, and the dermal flap was embedded in the pouch and fixed with orbicularis oculi muscle; After 1994, at the same time as the autologous dermal flap surgery, in order to further increase the amount of tissue in the upper lip, an ADM was implanted under the valve. Small wrinkles on the lips were removed with ablative surgery, resulting in a more stable surgical outcome [22]. ADM was made into a roll and transplanted between the submucosa of the red lip and the orbicularis oculi muscle, which increased the amount of lip tissue and increased the exposure of the red lip mucosa. After 3~12 months of follow-up, the lip activity was natural and the effect was satisfactory. There is a hardening sensation on the lips in the early stage, which disappears after 3 months. ADM was absorbed within 4~6 weeks after surgery, and then tended to stabilize [16].
5. Repair of tympanic membrane perforation: Two-sided tympanic membrane perforation model was made in the first phase of surgery using chinchilla rats as experimental animals, and tympanic membrane perforation repair was performed 3~4 weeks later. The perforated edges were reepidermized and repaired with autologous fascia and ADM (approximately 0.127 mm thick), respectively, resulting in vascular growth and opacity in ADM, which yielded the same survival rate and postoperative outcome as fascial transplantation, making it an ideal tympanic membrane substitute [23].
6. Ophthalmoplastic surgery: Monolithic grafts can be used as barrier/scaffold materials (e.g., primary or secondary graft covering), and multi-slice overlapping or roll grafts can be used for tissue filling (e.g., repair of periorbital soft tissue contour defects). There is unpredictable absorption in multiple overlapping or roll grafts, and overcorrection should be followed intraoperatively. Flexible ADM can repair meibomian defects, and the basement membrane is a natural substance for epithelial cell migration, favoring the growth of the binding membrane epithelium on its surface. The smooth basement membrane surface does not cause abrasion of the cornea. When the ADM is integrated with the bound membrane lining, there is no significant difference between the ADM and the surrounding tissue [6].
7. Repair of facial soft tissue defects: ADM has the dual characteristics of autologous tissue and allogeneic tissue transplantation. ADM was used early to fill facial soft tissue defects in adults [24], and then extended to children [12], including the nose, mandible, nasolabial folds, corners of the mouth, cheeks, and chin, involving soft tissue depressed deformities, dysplasia, tissue atrophy, and bony bulges. There are no serious complications such as infection, resorption and ADM prolapse, which is especially suitable for pediatric patients.
8. Others: Septal perforation repaired by ADM interspersed with a mucoperichondrous flap of the nasal septum can achieve the same therapeutic effect as autologous tissue repair [12,25]. ADM was grafted to the lower gingiva to thicken the gingiva and treat gingival recession with satisfactory results [26-29]. Bladder suspension for stress urinary incontinence using ADM has been shown to be the least invasive procedure of this type [30,31]. ADM was sutured into a tubular shape and interstitial between the femoral arteries of mice, and the vascular patency rate was 90 percent after 28 days, and an endothelial lining appeared on the ADM [32].
ADM can only be used as a repair of soft tissue defects, and has a certain degree of absorption, the cost is high, the clinical application time is limited, and its long-term effects and complications need to be further observed and studied.
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(Received:2001-01-15)