Successful reconstruction of full-thickness skin defects in a swine model using simultaneous split-thickness skin grafting and composite collagen microstructured dermal scaffolds.

Reconstitution of normal skin anatomy after full-thickness skin loss may be accomplished using a combination of a dermal regeneration template (DRT) and a split thickness skin graft (STSG). However, because of the relatively low rate of cell infiltration and vascularisation of currently available DRTs, reconstruction is almost always performed in a two-step procedure over the course of several weeks, resulting in multiple dressing changes, prolonged immobilisation and increased chance of infection. To mitigate the potential complications of this prolonged process, the collagen-based dermal template DermiSphere™ was developed and tested in a single-step procedure wherein DermiSphere and STSG were implanted simultaneously. When evaluated in a porcine, full thickness, excisional wound model, DermiSphere successfully supported simultaneous split thickness skin graft take and induced functional neodermal tissue deposition. When compared to a market leading product Integra Bilayer Wound Matrix, which was used in a multistep procedure (STSG placed 14 days after product implantation according to the product IFU), DermiSphere induced a similar moderate and transient inflammatory response that produced similar neodermal tissue maturity, thickness and vascularity, despite being implanted in a single surgical procedure leading to wound closure 2 weeks earlier. These data suggest that DermiSphere may be implanted in a single-step procedure with an STSG, which would significantly shorten the time course required for the reconstruction of both dermal and epidermal components of skin after full thickness loss.

Accelerated vascularization of a novel collagen hydrogel dermal template.

Full thickness skin loss is a debilitating problem, most commonly reconstructed using split thickness skin grafts (STSG), which do not reconstitute normal skin thickness and often result in suboptimal functional and esthetic outcomes that diminish a patient's quality of life. To address the minimal dermis present in most STSG, engineered dermal templates were developed that can induce tissue ingrowth and the formation of neodermal tissue. However, clinically available dermal templates have many shortcomings including a relatively slow rate and degree of neovascularization (∼2-4 weeks), resulting in multiple dressing changes, prolonged immobilization, and susceptibility to infection. Presented herein is a novel composite hydrogel scaffold that optimizes a unique scaffold microarchitecture with native hydrogel properties and mechanical cues ideal for promoting neovascularization, tissue regeneration, and wound healing. In vitro analysis demonstrated the unique combination of improved mechanical attributes with native hydrogel properties that promotes cell invasion and remodeling within the scaffold. In a novel 2-stage rat model of full thickness skin loss that closely mimics clinical practice, the composite hydrogel induced rapid cell infiltration and neovascularization, creating a healthy neodermis after only 1 week onto which a skin graft could be placed. The scaffold also elicited a gradual and favorable immune response, resulting in more efficient integration into the host. We have developed a dermal scaffold that utilizes simple but unique collagen hydrogel architectural cues that rapidly induces the formation of stable, functional neodermal tissue, which holds tremendous promise for the treatment of full thickness skin loss.

Magnetically actuated tissue engineered scaffold: insights into mechanism of physical stimulation.

Providing the right stimulatory conditions resulting in efficient tissue promoting microenvironment in vitro and in vivo is one of the ultimate goals in tissue development for regenerative medicine. It has been shown that in addition to molecular signals (e.g. growth factors) physical cues are also required for generation of functional cell constructs. These cues are particularly relevant to engineering of biological tissues, within which mechanical stress activates mechano-sensitive receptors, initiating biochemical pathways which lead to the production of functionally mature tissue. Uniform magnetic fields coupled with magnetizable nanoparticles embedded within three dimensional (3D) scaffold structures remotely create transient physical forces that can be transferrable to cells present in close proximity to the nanoparticles. This study investigated the hypothesis that magnetically responsive alginate scaffold can undergo reversible shape deformation due to alignment of scaffold's walls in a uniform magnetic field. Using custom made Helmholtz coil setup adapted to an Atomic Force Microscope we monitored changes in matrix dimensions in situ as a function of applied magnetic field, concentration of magnetic particles within the scaffold wall structure and rigidity of the matrix. Our results show that magnetically responsive scaffolds exposed to an externally applied time-varying uniform magnetic field undergo a reversible shape deformation. This indicates on possibility of generating bending/stretching forces that may exert a mechanical effect on cells due to alternating pattern of scaffold wall alignment and relaxation. We suggest that the matrix structure deformation is produced by immobilized magnetic nanoparticles within the matrix walls resulting in a collective alignment of scaffold walls upon magnetization. The estimated mechanical force that can be imparted on cells grown on the scaffold wall at experimental conditions is in the order of 1 pN, which correlates well with reported threshold to induce mechanotransduction effects on cellular level. This work is our next step in understanding of how to accurately create proper stimulatory microenvironment for promotion of cellular organization to form mature tissue engineered constructs.