Micrografting offers an alternative method to traditional split-thickness skin grafting for coverage of wounds. Currently, the most accepted indication for its use is for large burn wounds when donor sites are limited. The overwhelming majority of published reports have studied micrograft application to burn wounds, but few other types of wounds have been examined using micrograft techniques. With the exception of several early reports of pinch grafting for chronic ulcer healing, no studies utilizing micrograft techniques on diabetic ulcers or pressure ulcers have been published. Moreover, only a few randomized trials that investigate micro-grafting versus traditional mesh grafting and/or tissue-engineered skin exist in the literature. It would seem appropriate to perform a large, prospective, multicenter trial to fully investigate if micrografting has a role in the wound healing armamentarium.
The lack of popularity with micrografting is partly due to increased scar contracture formation. Quantification of wound healing mediators and proteins at different stages of the healing process when using micrografts has not been investigated. Previous studies have demonstrated that cytokines and growth factors such as platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), basic fibroblast growth factor, and epidermal growth factor (EGF) promote fibroblast chemotactic migration in vitro
It would be interesting to see if there is an upregulation or downregulation of these cytokines and growth factors at different phases of wound healing to better understand the healing process of micrografts compared to standard mesh grafts, if any. Protein (collagen I and III, fibronectin, procollagens) and enzyme expression (matrix metalloproteinases and tissue inhibitors of metalloproteinases) involved with extracellular matrix changes at different stages of wound healing would also need to be investigated as to why excessive contracture formation occurs.
Genetic engineering strategies to enhance in vivo
cutaneous regeneration and wound healing have been investigated.81–88
Using deoxyribonucleic acid delivery techniques to modify gene expression such as EGF,84,85
and keratinocyte growth factor91
could be applied to micrografts to further clarify the molecular mechanisms involved with micrograft healing. These molecular details of micrograft wound healing could potentially yield new ideas and technologies designed to decrease scar contracture formation.
A wide range of adjunctive clinical possibilities to enhance micrograft efficiency needs to be investigated. For example, mechanical pressure therapy has been demonstrated to be effective in causing regression of hypertrophic scarring in 60–85% of patients.92
Mechanical pressure itself rather than simple scar occlusion by the pressure dressing has been shown to be necessary for scar reduction in a comparison of low versus normal pressure therapy.93
In fact, several studies have reported that pressures >25 mm Hg decreases scar edema, vascularity, mucopolysaccharide production, mast cell degranulation, oxygen saturation, myofibroblast proliferation, and increases collagen bundle rearrangement.92,94,95
During micrograft healing, pressure therapy could potentially help reduce scar formation, especially during the early phases of wound healing, as it is widely recognized that pressure therapy is most effective at the early stages of graft and scar contracture formation.96,97
Negative pressure wound therapy (NPWT) using vacuum-assisted devices have been used extensively with skin grafts, and NPWT’s role in the healing of complex wounds has been documented with increased graft take due to total immobilization of the graft, thereby limiting shear forces, elimination of fluid collections, bridging of the graft, and decreasing bacterial contamination.98–102
Enhanced quality of wound appearance has been noted using NPWT with skin grafts.103
However, NPWT has not been evaluated with micrografts. Characterization of micrograft adherence and mechanical stability with NPWT would need to be studied.
Combination therapy with micrografting and CEA has been investigated by several groups.61,104
The use of CEA holds promise in creating less scar within the wound, because a greater wound area has to be re-epithelialized.42
The healing rate may be enhanced with CEA, because cells with high proliferative capacity can be selected during culture. Also, the culture conditions can be manipulated and controlled to enhance viability and proliferative potential.
An avenue of potential interest is the use of biodegradable scaffolds combined with a micrograft overlay. The use of Integra as a dermal regeneration template prior to micrograft application has been previously described.67,68
Many biologic, bioartificial, and synthetic scaffolds are used in wound healing for their extracellular matrix-mimicking properties.105,106
Cadaveric acellular dermis has been used extensively for facilitating wound and soft-tissue defect coverage, with one report used with micrografting.51
Hydrogel therapy is another extracellular matrix-like modality that offers several advantages because it is easy to use, nonadherent, and virtually painless on application.107–109
Hydrogels have an added advantage in that they can be injected or preprepared with medications and antibiotics. Also, hydrogels provide graft immunologic protection in the host that could be of interest in micrografting of allogenic skin. Micrograft immersion in a hydrogel with proper permeability that allows diffusion and transport of oxygen, essential nutrients, metabolic waste, and secretory products could provide an easily applicable protective scaffold for the micrografts to communicate in.
Finally, efficient harvesting, preparation, and delivery techniques need to be developed for mainstream micrograft use. Specialized dermatomes and cutting surfaces are being used for the creation of micrografts, but the procedures require more personnel and operating time compared to standard mesh-graft techniques. Delivery methods such as a spray have been introduced; however, other methods such as gel immersion or macroencapsulation are being investigated in our lab.
Micrografting is a conceptually appealing strategy for wound coverage; however, appropriate studies to identify its true potentials and pitfalls are severely lacking. Complex wounds such as diabetic ulcers may benefit from micrografting techniques because of smaller donor sites needed to cover a larger wound area; however, the various micrograft techniques may need to be compared for a wide range of wounds to discern which technique is clinically beneficial for the particular type of wound. Experimental studies are also needed to characterize the micrografts’ physiological and biomechanical behavior compared to standard mesh grafting both in vitro and in vivo. For now, however, the simplicity of the approach, true expansion ratio, and applicability when donor sites are limited make micrografting a useful tool for surgeons to use on large or complex wounds.