Introduction

Skin grafting is a surgical technique used to replace damaged or missing skin with healthy skin. This procedure is commonly used in various medical fields, including dermatology, plastic surgery, and burn care. The primary objective of skin grafting is to provide a protective covering for a wound or an area where the skin has been lost [1]. Skin grafts help prevent infection, reduce fluid loss, and stimulate the formation of new blood vessels and tissue formation. They aid in wound healing and improve the functionality and appearance of the affected area [2]. Skin grafts can be particularly beneficial in cases where the body’s natural healing ability is compromised or when the wound is extensive. Skin grafts treat various conditions such as burns, traumatic injuries, chronic ulcers, surgical wounds, and congenital defects, among others [3].

Autologous skin grafting, including epidermal, split-thickness, and full-thickness grafting techniques, involves the transfer of a patient’s skin from one area of their body to another. Cellular and tissue-based products (CTPs) are bioengineered products that mimic the structure and function of natural skin and are used to stimulate wound healing [4, 5]. A new term, cellular, acellular, and matrix-like products (CAMPs), has been proposed to better encompass the array of products now available [6]. Allograft skin grafting involves the use of donor skin from another individual or cadaver. Allografts are used as temporary covers to promote wound healing until the body can replace the graft with its own tissue.

Dermatologists often manage a variety of acute and chronic wounds that may require grafting for adequate healing [3, 7]. This review will provide an overview of skin grafting, special considerations involved in graft choice, different types of skin grafts and substitutes, and the latest advancements in this field.

Skin Grafting History

Skin grafting has a long history dating back 3500 years ago and has undergone significant development over time [8]. Ancient civilizations such as the Indians, Egyptians, and Romans used rudimentary techniques to apply skin from one body part to another. Sushruta, an ancient Indian physician, is considered the “father of surgery” and described techniques for reconstructing damaged noses and ears using skin grafts. Gaspare Tagliacozzi also developed techniques for reconstructing noses using skin grafts in the sixteenth and seventeenth centuries. In the nineteenth century, advancements in anesthesia and aseptic practices enabled more complex skin grafting procedures to be performed [9]. In the twentieth century, plastic and reconstructive surgery became established medical specialties leading to further refinement of skin grafting techniques. Innovations in tissue culture and graft preservation have improved the success and outcomes of skin grafting procedures [9]. Additionally, tissue engineering and regenerative medicine have introduced new possibilities for the development of laboratory-grown [10]. Today, skin grafting is a widely used procedure in various surgical fields, with continuous improvement in techniques and technologies providing better outcomes and enhanced patient care.

Special Considerations for Skin Grafting

Clinicians often utilize grafts as a treatment option for repairing, reconstructing, or improving various skin wounds. Skin grafts become necessary when other treatments have proven ineffective or when there is a need to replace extensively damaged or lost skin. Dermatologists may use skin grafts after Mohs micrographic surgery to repair surgical defects and promote healing. In some cases of refractory vitiligo, grafting healthy skin from unaffected areas can help restore skin color [11,12,13]. Skin grafts can treat chronic ulcers, such as venous leg ulcers or pressure ulcers, that have not responded to other therapies. Grafts can also be used for cosmetic or functional purposes.

The decision to use a graft depends on factors such as the patient’s overall health, the specific skin condition being treated, the location and size of the affected area, and the likelihood of graft success [14]. Factors such as underlying medical conditions, allergies, medications, and lifestyle habits can impact healing. Dermatologists should carefully assess each case and determine the most appropriate treatment plan, which may involve grafts and other adjunct dermatologic procedures [15, 16]. Different types of grafts, like split-thickness grafts (STSGs) or full-thickness grafts (FTSGs), have varying degrees of success and are appropriate for different situations [7].

When selecting a donor site for a graft, it is helpful to choose the skin that matches the color, texture, and thickness of the recipient site. Adequate blood supply at the recipient site is also necessary for graft survival [3, 7]. Proper planning of the size and shape of the graft is essential to ensure good coverage and minimize tension, which can impact healing. It is important to note that chronic wounds are colonized, and assessing for infection and biofilm development and ensuring proper wound bed preparation are needed for graft survival. Preparing the recipient site should involve the removal of dead tissue and debris and thoroughly cleaning and dressing the wound [16]. Finally, proper graft fixation is necessary to prevent movement and ensure adequate contact between the graft and the recipient site. Techniques such as sutures, staples, or adhesive agents may achieve this. Additionally, bolster dressings, including negative pressure wound therapy (NPWT), may be used to increase the graft’s contact with the wound bed [17].

Autologous Skin Grafts

An autologous skin graft involves the transfer of skin from a specific donor area to a target site within the same individual. This method is frequently used for skin reconstruction across various medical conditions. Autografts can be extracted either as STSGs or FTSGs, offering flexibility in graft thickness selection based on the defect.

Epidermal Grafting

Epidermal grafting (EG) is a type of autologous skin grafting where the epidermal layer is extracted from the donor area. EG is achieved by gently applying heat and consistent negative pressure to healthy skin, inducing the formation of blisters. The top layer of the blister, comprising the epidermis, is then removed and transplanted onto the wound site. Notably, the procedure maintains the untouched dermal layer at the donor site, ensuring the donor site heals without scarring and with minimal pain [18]. Consequently, this procedure permits outpatient autologous skin grafting without even local anesthesia. Studies have demonstrated promising outcomes in acute wounds, chronic ischemic and diabetic foot ulcers, pyoderma gangrenosum, and ulcers associated with autoimmune connective tissue diseases [19,20,21,22,23]. Additionally, this technique has been extensively investigated in vitiligo cases, with studies indicating enhanced pigmentation and improved esthetic outcomes.

Split-Thickness Skin Grafting

STSGs involves harvesting a thin layer of skin that includes the epidermis and a portion of the underlying dermis from a designated donor site [24]. STSGs can effectively cover large areas of damaged skin with better survival characteristics due to reduced nutritional requirements compared to FTSGs [24]. In dermatology, STSGs are often utilized for wound healing and reconstructive purposes [25]. It is worth noting that in scenarios involving significant chronic wounds, burn patients, or sizable defects, it is possible to complement split-thickness skin grafting with CTPs. This combined approach aids in preparing the wound bed for graft integration, thereby increasing the likelihood of a successful graft outcome and reducing the necessary graft size [26]. While STSGs confer benefits such as expedited wound healing, they may lead to color, texture, and durability mismatch [25, 27]. STSGs also face higher risks of contracture and tend to be more painful than FTSGs for patients [24, 27].

Depending on graft size and patient preference, STSGs can be performed under local or general anesthesia. The most common donor sites for wounds below the neck are the lateral thigh or trunk due to their broad surface and discrete location [25]. There are a few different techniques to harvest the donor tissue detailed below:

Dermatome Utilization

To harvest a uniform depth graft, surgeons often use an air or electric-powered dermatome, an oscillating blade tool [24, 25]. The skin is cleaned and prepped with mineral oil to optimize gliding, and the dermatome initiates contact with the skin at 45° and then flattened and pulled across the skin to harvest the proper size and depth necessary [25].

Meshing Technique

Dermatomal harvesting is often complemented with meshing, a technique involving the introduction of perforations into the graft by a hand-cranked machine [25]. Meshing facilitates the expansion of the graft, with a greater meshing ratio resulting in increased graft stretch [25]. This process allows for a smaller donor site to cover a larger wound area; however, it may also delay healing due to the additional required epithelization time [25].

Pinch Grafting

Miniature or micro-sized grafts are harvested from the donor site and placed in the recipient wound for smaller defects. The grafts can be raised by forceps or by injecting local anesthetic underneath the tissue to create a small wheal for shave removal [24, 28].

Once the wound bed is prepared and the graft is in place, the graft can be secured with sutures/staples or steri-strips in case of pinch grafting and covered with a pressure dressing [25].

Full-Thickness Skin Graft

FTSGs involve harvesting a complete section of skin that encompasses both the epidermis and the entire dermis from a donor site [29]. This graft provides a closer match in color and texture to the surrounding skin [27]. Common donor sites include the preauricular and postauricular regions, the supraclavicular fossa, and the inner arm [29]. However, due to significant donor site morbidity, FTSGs in dermatology are typically limited to small, well-vascularized surgical wounds [27, 29]. FTSGs are commonly used to repair Mohs defects [30•]. In FTSGs, the donor tissue is harvested free hand via a scalpel, and the donor site is closed with sutures [31]. Adipose tissue, if present, is trimmed from the graft, and the graft is secured to the wound via sutures, ensuring adequate contact with the wound bed [29, 30•]. A surgical bolster and pressure dressing are typically applied to the surgical site to support inosculation [30•].

Cultured Epidermal Autografts

Bioengineered skin products, or cultured epidermal autografts (CEAs), are an advanced technique for treating wounds or skin injuries. The process involves growing a patient’s skin cells in a laboratory, which are then transplanted onto the wound site. These cultured cells are placed on a scaffold to promote healing, minimize scarring, and enhance overall recovery [32]. Unlike traditional grafts, CEAs require a smaller donor sample, reducing morbidity at the donor site. However, the procedure’s complexity and time requirements are significant challenges that accompany its potential benefits.

Cellular and Tissue-Based Products

CTPs are specialized medical products developed to support the healing of a variety of wounds. These products mimic the role of natural skin, providing protection, promoting tissue repair, and assisting in regenerating damaged or lost skin. CTPs can be classified in multiple ways but will be categorized herein as follows:

  1. 1.

    Human skin allografts

  2. 2.

    Allogeneic matrices

  3. 3.

    Composite matrices

  4. 4.

    Acellular matrices

Robust randomized clinical trials focusing on skin substitutes remain sparse; selected studies will be highlighted within each distinct subsection below.

Human Skin Allografts

Human skin allografts involve the transplantation of skin tissue from one person to another. These grafts are typically used as temporary wound covers to provide protection, reduce pain, and promote healing. Human skin allografts are often sourced from cadaveric donors. While they can help create a conducive environment for wound healing, they are eventually rejected by the recipient’s immune system due to genetic differences. They serve as a short-term solution until the recipient’s skin can regenerate.

Allogeneic Matrices

Allogeneic matrices are derived from human neonatal fibroblasts obtained from foreskin tissue, which may contain metabolically active or regenerative elements. These matrices are primarily used to provide support for soft tissues, and a subset has gained approval for treating cases of full-thickness skin and soft tissue loss. This category also encompasses products sourced from amnion, chorion, placenta, or umbilical cord.

A well-studied allogeneic matrix is comprised of a dehydrated human amnion/chorion membrane (dHACM) derived from placental tissues. Clinical trials consistently highlighted their potential for chronic wound healing, particularly in cases of diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) [33,34,35]. Placenta-derived dHACM matrices effectively promote complete healing, reduce healing time, and improve wound size reduction for DFUs compared to standard care [36,37,38,39,•, 37,38,39,40,41], even in complex DFUs or those with exposed tendon or bone [41, 42]. Additionally, placenta-derived dHACM enhances VLU treatment, accelerating complete healing and reducing time to healing compared to standard or compression therapy alone [35, 43].

When compared to a bovine-derived allogenic matrix, placenta-derived dHACMs demonstrated superiority among DFU patients, with higher wound closure rates, cost-effectiveness, and faster healing [44, 45]. Typically, placenta-derived dHACM application involves debridement, attaching the material with adhesive strips, and wound care, with reapplication assessments typically after 3–4 weeks. They offer a favorable safety profile, with no significant difference in adverse events compared to standard care [33]. Their advantages include accessibility, ease of use, minimal complications, cost-effectiveness, and potential pain reduction [33, 34, 46]. Nonetheless, further research should continue to investigate graft sourcing, preservation techniques, and the impact of clinical application on patient outcomes [47].

While dHACMs are formed by dehydrating placental tissue, there is another form of placental allogenic matrix which is made by cryopreserving intact human placental membranes (vCPM) [48]. In vCPMs, preserve placental membrane components, including viable endogenous cells in their native state. vCPMs have consistently demonstrated improved wound healing in patients with DFUs and VLUs [49]. In a comparison study with dHACMs, vCPMs revealed greater clinical effectiveness, notably significantly higher closure rates. This enhanced performance can be attributed, in part, to vCPMs preservation of the native matrix, which conserves its intrinsic functionality, including structural integrity and the biological composition of essential signaling molecules [50].

Composite Matrices

Composite matrices combine different types of materials to mimic the layered structure of natural skin. These matrices often consist of both synthetic and biological components. For example, a composite matrix might have a synthetic top layer as a protective barrier and a lower allogeneic or acellular matrix layer to support tissue regeneration. The design aims to provide immediate wound coverage and a conducive environment for tissue regrowth.

Studies with composite matrices have shown promising results in treating venous leg ulcers and diabetic foot ulcers [51]. These CTPs have demonstrated their efficacy in promoting wound closure, enhancing quality of life by reducing pain symptoms, and significantly lowering the incidence of osteomyelitis and amputations. Additionally, studies have demonstrated that when combined with autograft, composite matrices accelerate wound closure and improve tissue cosmetic appearance in burn patients compared to autograft alone [52]. However, these types of grafts are associated with high costs and have mainly been studied in recalcitrant wounds, which may limit their generalizability [53].

Acellular Matrices

Acellular matrices are tissue substitutes processed to remove cellular components while retaining the extracellular matrix. These matrices can come from various sources, including human or animal tissues. Removing cells eliminates the risk of immune rejection and allows the recipient’s cells to repopulate the matrix. Acellular matrices serve as scaffolds for cell migration, tissue remodeling, and angiogenesis, ultimately aiding wound healing and tissue regeneration.

Acellular products are most commonly constituted from porcine and bovine tissue and are used across a wide spectrum of wounds. Randomized trials have demonstrated their effectiveness in improving wound healing, with reported success in pressure ulcers, DFUs, VLUs, mixed ulcers, and in burn injuries [54,55,56,57,58,59,60,61].

Novel Techniques

Bioprinting

Bioprinting, a newly developed tissue engineering strategy, creates three-dimensional CTPs that can be personalized to suit the patient’s needs and wound characteristics [62]. It involves depositing biomaterials, living cells, and growth factors layer by layer using computer-aided design (CAD) [63]. Bioprinting allows precise control over parameters like pore size, interconnectivity, and ECM density, promoting cell adhesion and viability [63]. It can replicate the complex microarchitecture of skin and enable the production of functional artificial skin constructs [63]. Current research is investigating the potential of impregnating bioprinted graft tissue with stem cells to increase tissue vascularization and promote long-term graft survival [62, 64, 65]. Bioprinting shows promise in replicating the stratified epidermis but has not fully expanded to replicating the dermis [66].

Wound Care

During the initial stage after the skin grafting procedure, it is crucial to maintain a delicate balance between safeguarding the graft and avoiding excessive movement. This is necessary to promote the adhesion of the graft and minimize the chances of compromising the reconstruction. Other adjunctive therapies, like NPWT, can be used in cases of large skin defects [67•, 68]. Proper wound dressings are also crucial for ensuring successful skin grafts. Dressings play a vital role in protecting the graft site, regulating moisture levels, preventing infections, and promoting overall wound healing. The choice of dressing depends on various factors, such as the type and location of the graft, the patient’s health, and available resources. Additionally, certain dressings impregnated with antimicrobial properties, such as silver, iodine, and honey, can be used to reduce bacterial burden [69, 70]. However, their application in grafts with live cells requires careful consideration due to the potential risk of cytotoxicity. Dressing types are listed by increasing absorbency capability, indications, and commercially available examples (Table 1).

Table 1 Dressing types are listed based on the level of absorbency, indications, and commercially available products
Full size table

Conclusion

Skin grafting can be a complex procedure that requires careful planning, preparation, and postoperative care. The success of the graft depends on factors like the choice of graft type, proper wound management, the patient’s overall health, and comorbidities. Skin grafts have evolved significantly over time, aided by advancements in surgical techniques, bioengineered products, and wound care, as they continue to be an essential tool for wound healing.