Repair of Compound Dorsal Defects of the Digits Using a Free Antegrade Palmaris Longus Tendocutaneous Venous Flap.

PURPOSE: To investigate the clinical effect of repairing small dorsal digit compound tissue defects using a free palmaris longus tendocutaneous flap nourished by venous blood. METHODS: In a retrospective analysis of patients treated between March 2010 and October 2017, 18 patients were identified as having small compound tissue defects, which were repaired using a free palmaris longus tendocutaneous flap nourished by venous blood. The average age of the patients, including 15 male and 3 female patients, was 34 years (range, 22-55 years). The mean wound size was 6 cm2 (range, 2.0 × 1.5 to 3.5 × 2.0 cm2). All the patients had dorsal defects. The average length of extensor tendon defect was 2.0 cm (range, 1.0-3.0 cm). The mean area of the flap was 7 cm2 (range, 2.5 × 2.0 to 4.0 × 3.5 cm2). The donor sites were primarily closed. RESULTS: All 18 flaps survived. A vascular crisis due to a venospasm occurred within 48 hours in 3 flaps, but ultimately, all the flaps survived. The patients were followed-up for a mean period of 10 months (range, 3-15 months). All the patients returned to their previous work after 10-12 weeks. No pain or scar contracture was reported in either the recipient or donor site. CONCLUSIONS: The free antegrade palmaris longus tendocutaneous venous flap enabled the repair of compound tissue defects of the dorsal digit, resulting in acceptable aesthetics, repaired tendon defects, and wound coverage. This surgical method is an option for the reconstruction of small compound defects of digits with extensor defects. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Solid Organ Bioprinting: Strategies to Achieve Organ Function.

The field of tissue engineering has advanced over the past decade, but the largest impact on human health should be achieved with the transition of engineered solid organs to the clinic. The number of patients suffering from solid organ disease continues to increase, with over 100 000 patients on the U.S. national waitlist and approximately 730 000 deaths in the United States resulting from end-stage organ disease annually. While flat, tubular, and hollow nontubular engineered organs have already been implanted in patients, in vitro formation of a fully functional solid organ at a translatable scale has not yet been achieved. Thus, one major goal is to bioengineer complex, solid organs for transplantation, composed of patient-specific cells. Among the myriad of approaches attempted to engineer solid organs, 3D bioprinting offers unmatched potential. This review highlights the structural complexity which must be engineered at nano-, micro-, and mesostructural scales to enable organ function. We showcase key advances in bioprinting solid organs with complex vascular networks and functioning microstructures, advances in biomaterials science that have enabled this progress, the regulatory hurdles the field has yet to overcome, and cutting edge technologies that bring us closer to the promise of engineered solid organs.

Advances in Skin Tissue Engineering and Regenerative Medicine.

There are an estimated 500,000 patients treated with full-thickness wounds in the United States every year. Fire-related burn injuries are among the most common and devastating types of wounds that require advanced clinical treatment. Autologous split-thickness skin grafting is the clinical gold standard for the treatment of large burn wounds. However, skin grafting has several limitations, particularly in large burn wounds, where there may be a limited area of non-wounded skin to use for grafting. Non-cellular dermal substitutes have been developed but have their own challenges; they are expensive to produce, may require immunosuppression depending on design and allogenic cell inclusion. There is a need for more advanced treatments for devastating burns and wounds. This manuscript provides a brief overview of some recent advances in wound care, including the use of advanced biomaterials, cell-based therapies for wound healing, biological skin substitutes, biological scaffolds, spray on skin and skin bioprinting. Finally, we provide insight into the future of wound care and technological areas that need to be addressed to support the development and incorporation of these technologies.

Bioprinting a skin patch with dual-crosslinked gelatin (GelMA) and silk fibroin (SilMA): An approach to accelerating cutaneous wound healing.

Clinical settings often face significant obstacles in treating large acute wounds. The alternative of therapeutic approach is needed urgently. Hydrogels derived from natural or synthetic materials may be designed to perform a variety of functions for promoting wound healing. Herein, a 3D bioprinted hydrogel patch is designed for accelerating acute wound healing, which is fabricated with methacryloyl-substituted gelatin (GelMA) and silk fibroin (SilMA) dual-cross-linked by ultraviolet (UV) light. The GelMA with added silk fibroin (GelSilMA) shows improved biodegradation and mechanical properties. Furthermore, SilMA hydrogel can maintain a moisturized healing environment in wound area persistently with adequate degradation capacity. In vivo, GelSilMA (G-S) hydrogel can help to speed wound closure by the improved microenvironment for epidermal tissue regeneration and endogenous collagen generation accordingly. In summary, the G-S hydrogel patch can accelerate acute wound healing efficiently in a relatively simple and inexpensive manner.

Multicellular bioprinted skin facilitates human-like skin architecture in vivo.

Bioprinting is a promising alternative method to generate skin substitutes because it can replicate the structural organization of the skin into biomimetic layers in vitro. In this study, six primary human skin cell types were used to bioprint a trilayer skin construct consisting of epidermis, dermis, and hypodermis. Transplantation of the bioprinted skin with human cells onto full-thickness wounds of nu/nu mice promoted rapid vascularization and formation of epidermal rete ridges analogous to the native human epidermis, with a normal-looking extracellular matrix. Cell-specific staining confirmed the integration of the implanted cells into the regenerated skin. Using a similar approach, a 5 centimeter-by-5 centimeter bioprinted autologous porcine skin graft was transplanted onto full-thickness wounds in a porcine excisional wound model. The bioprinted skin graft improved epithelialization, reduced skin contraction, and supported normal collagen organization with reduced fibrosis. Differential gene expression demonstrated pro-remodeling protease activity in wounds transplanted with bioprinted autologous skin grafts. These results demonstrate that bioprinted skin can support skin regeneration to allow for nonfibrotic wound healing and suggest that the skin bioprinting technology may be applicable for human clinical use.

Decellularized Skin Extracellular Matrix (dsECM) Improves the Physical and Biological Properties of Fibrinogen Hydrogel for Skin Bioprinting Applications.

Full-thickness skin wounds are a significant clinical burden in the United States. Skin bioprinting is a relatively new technology that is under investigation as a new treatment for full-thickness injuries, and development of hydrogels with strong physical and biological characteristics are required to improve both structural integrity of the printed constructs while allowing for a more normal extracellular matrix milieu. This project aims to evaluate the physical and biological characteristics of fibrinogen hydrogel supplemented with decellularized human skin-derived extracellular matrix (dsECM). The hybrid hydrogel improves the cell viability and structural strength of bioprinted skin constructs. Scanning electron microscopy demonstrates that the hybrid hydrogel is composed of both swelling bundles interlocked in a fibrin network, similar to healthy human skin. This hybrid hydrogel has improved rheological properties and shear thinning properties. Extrusion-based printing of the fibrinogen hydrogel + dsECM demonstrates significant improvement in crosshatch pore size. These findings suggest that incorporating the properties of dsECM and fibrinogen hydrogels will improve in vivo integration of the bioprinted skin constructs and support of healthy skin wound regeneration.

3D Bioprinted Highly Elastic Hybrid Constructs for Advanced Fibrocartilaginous Tissue Regeneration.

Advanced strategies to bioengineer a fibrocartilaginous tissue to restore the function of the meniscus are necessary. Currently, 3D bioprinting technologies have been employed to fabricate clinically relevant patient-specific complex constructs to address unmet clinical needs. In this study, a highly elastic hybrid construct for fibrocartilaginous regeneration is produced by co-printing a cell-laden gellan gum/fibrinogen (GG/FB) composite bioink together with a silk fibroin methacrylate (Sil-MA) bioink in an interleaved crosshatch pattern. We characterize each bioink formulation by measuring the rheological properties, swelling ratio, and compressive mechanical behavior. For in vitro biological evaluations, porcine primary meniscus cells (pMCs) are isolated and suspended in the GG/FB bioink for the printing process. The results show that the GG/FB bioink provides a proper cellular microenvironment for maintaining the cell viability and proliferation capacity, as well as the maturation of the pMCs in the bioprinted constructs, while the Sil-MA bioink offers excellent biomechanical behavior and structural integrity. More importantly, this bioprinted hybrid system shows the fibrocartilaginous tissue formation without a dimensional change in a mouse subcutaneous implantation model during the 10-week postimplantation. Especially, the alignment of collagen fibers is achieved in the bioprinted hybrid constructs. The results demonstrate this bioprinted mechanically reinforced hybrid construct offers a versatile and promising alternative for the production of advanced fibrocartilaginous tissue.

Bioprinted Skin Recapitulates Normal Collagen Remodeling in Full-Thickness Wounds.

Over 1 million burn injuries are treated annually in the United States, and current tissue engineered skin fails to meet the need for full-thickness replacement. Bioprinting technology has allowed fabrication of full-thickness skin and has demonstrated the ability to close full-thickness wounds. However, analysis of collagen remodeling in wounds treated with bioprinted skin has not been reported. The purpose of this study is to demonstrate the utility of bioprinted skin for epidermal barrier formation and normal collagen remodeling in full-thickness wounds. Human keratinocytes, melanocytes, fibroblasts, dermal microvascular endothelial cells, follicle dermal papilla cells, and adipocytes were suspended in fibrinogen bioink and bioprinted to form a tri-layer skin structure. Bioprinted skin was implanted onto 2.5 × 2.5 cm full-thickness excisional wounds on athymic mice, compared with wounds treated with hydrogel only or untreated wounds. Total wound closure, epithelialization, and contraction were quantified, and skin samples were harvested at 21 days for histology. Picrosirius red staining was used to quantify collagen fiber orientation, length, and width. Immunohistochemical (IHC) staining was performed to confirm epidermal barrier formation, dermal maturation, vascularity, and human cell integration. All bioprinted skin treated wounds closed by day 21, compared with open control wounds. Wound closure in bioprinted skin treated wounds was primarily due to epithelialization. In contrast, control hydrogel and untreated groups had sparse wound coverage and incomplete closure driven primarily by contraction. Picrosirius red staining confirmed a normal basket weave collagen organization in bioprinted skin-treated wounds compared with parallel collagen fibers in hydrogel only and untreated wounds. IHC staining at day 21 demonstrated the presence of human cells in the regenerated dermis, the formation of a stratified epidermis, dermal maturation, and blood vessel formation in bioprinted skin, none of which was present in control hydrogel treated wounds. Bioprinted skin accelerated full-thickness wound closure by promoting epidermal barrier formation, without increasing contraction. This healing process is associated with human cells from the bioprinted skin laying down a healthy, basket-weave collagen network. The remodeled skin is phenotypically similar to human skin and composed of a composite of graft and infiltrating host cells. Impact statement We have demonstrated the ability of bioprinted skin to enhance closure of full-thickness wounds through epithelialization and normal collagen remodeling. To our knowledge, this article is the first to quantify collagen remodeling by bioprinted skin in full-thickness wounds. Our methods and results can be used to guide further investigation of collagen remodeling by tissue engineered skin products to improve ongoing and future bioprinting skin studies. Ultimately, our skin bioprinting technology could translate into a new treatment for full-thickness wounds in human patients with the ability to recapitulate normal collagen remodeling in full-thickness wounds.