3D Bioprinted Human Skin Model Recapitulating Native-Like Tissue Maturation and Immunocompetence as an Advanced Platform for Skin Sensitization Assessment.

Physiologically-relevant in vitro skin models hold the utmost importance for efficacy assessments of pharmaceutical and cosmeceutical formulations, offering valuable alternatives to animal testing. Here, an advanced immunocompetent 3D bioprinted human skin model is presented to assess skin sensitization. Initially, a photopolymerizable bioink is formulated using silk fibroin methacrylate, gelatin methacrylate, and photoactivated human platelet releasate. The developed bioink shows desirable physicochemical and rheological attributes for microextrusion bioprinting. The tunable physical and mechanical properties of bioink are modulated through variable photocuring time for optimization. Thereafter, the bioink is utilized to 3D bioprint "sandwich type" skin construct where an artificial basement membrane supports a biomimetic epidermal layer on one side and a printed pre-vascularized dermal layer on the other side within a transwell system. The printed construct is further cultured in the air-liquid interface for maturation. Immunofluorescence staining demonstrated a differentiated keratinocyte layer and dermal extracellular matrix (ECM)-remodeling by fibroblasts and endothelial cells. The biochemical estimations and gene-expression analysis validate the maturation of the printed model. The incorporation of macrophages further enhances the physiological relevance of the model. This model effectively classifies skin irritative and non-irritative substances, thus establishing itself as a suitable pre-clinical screening platform for sensitization tests.

Omentum Extracellular Matrix-Silk Fibroin Hydroscaffold Promotes Wound Healing through Vascularization and Tissue Remodeling in the Diabetic Rat Model.

Nonhealing diabetic wounds are often associated with significant mortality and cause economic and clinical burdens to the healthcare system. Herein, a biomimetic hydroscaffold is developed using omentum tissue-derived decellularized-extracellular matrix (dECM) and silk fibroin (SF) proteins that associate the behavior of a collagenous fibrous scaffold and a hydrogel to reproduce all aspects of the provisional skin tissue matrix. The chemical cross-linker-free in situ gelation property of the two types of SF proteins from Bombyx mori and Antheraea assamensis ensures the adherence of dECM with surrounding tissue on the wound bed, circumventing further suturing. The physicochemical and mechanical properties of the composite hydroscaffold (SF-dECM) were thoroughly evaluated. The hydroscaffolds were found to support the growth and proliferation of human dermal fibroblasts and influence the angiogenic potential of endothelial cells under in vitro conditions. Furthermore, the healing efficacy of the composites was evaluated by generating full-thickness wounds on a streptozotocin-induced diabetic rat model. The presence of dECM components in the composite facilitated the rate of wound closure, granulation tissue formation, and re-epithelialization by providing intrinsic cues to advance the inflammatory stage and stimulating angiogenesis. Collectively, as an off-the-shelf wound dressing requiring only a single topical administration, the SF-dECM hydroscaffold is a promising, cost-effective dressing for the management of chronic diabetic wounds.

Controlled nano Cu precipitation through age treatment: A method to enhance the biodegradation, mechanical, antimicrobial properties and biocompatibility of Fe-20Mn-3Cu alloys.

Iron-manganese (Fe-Mn) based degradable biomaterials have been proven as a suitable substitute to permanent internal fracture-fixation devices. However, lower degradation and bacterial infection are still major concerns. To overcome these limitations, in this work, we have incorporated copper (Cu) in Fe-Mn system. The objective is to produce Cu nano-precipitates and refined microstructure through suitable combination of cold-rolling and age-treatment, so that degradation is improved eventually. High resolution transmission electron microscope (TEM) and scanning transmission electron microscope (STEM) confirmed the Cu rich composition of the nano-precipitates. Number of precipitates increased as aging time increased. Three-dimensional visualization of Fe, Mn and Cu atomic distributions using atom probe tomography (APT), indicated that Cu precipitates were in 15-50 nm range. Large number of nano-precipitates along with lower dislocation density led to highest strength (1078 MPa) and ductility (37 %) for the 6 h age-treated sample. On the other hand, nano-precipitates and refined microstructure resulted highest degradation for the 12 h of age treated sample (0.091 mmpy). When E.Coli bacteria was cultured with the sample extract, significantly higher antibacterial efficacy was observed for the sample having higher nano-precipitates. Higher degradation rate did not cause cyto-toxicity, rather promoted statistically higher cell proliferation (1.5 times within 24 h) in in vitro cell-material interaction studies. In vivo biocompatibility of the alloy containing large nano-precipitates was confirmed from higher new bone regeneration (60%) in rabbit femur model. Overall study suggested that the optimization of the thermo-mechanical processes can effectively tailor the Fe-Mn-Cu alloys for successful internal fracture fixation. STATEMENT OF SIGNIFICANCE: In the present work, we have reported a noble thermo-mechanical approach to simultaneously achieve Cu nano-precipitates and grain refinement in Fe-20Mn-3Cu alloy.

Silk-based phyto-hydrogel formulation expedites key events of wound healing in full-thickness skin defect model.

Immense socio-economic burden of chronic wound demands effective, low-cost strategies for wound care. Herein, we have developed a chemical crosslinker-free phyto-hydrogel by encapsulating phytochemicals of Aloe vera mucilage extract (AVM) in the self-assembled polymeric chains of two different silk fibroin (SF) proteins (from Bombyx mori and Antheraea assamensis). Additionally, polyvinylpyrrolidone (PVP) has been used as a stabilizer that also contributed to the mucoadhesive property of the composite (SAP; made of SF, AVM, and PVP) hydrogel. The physicochemical properties of the hydrogel were evaluated and compared with SF hydrogel containing only SF proteins without any additives. The biocompatibility assessment of the hydrogel under in vitro conditions has shown improved cellular proliferative and migratory responses, suggesting faster tissue repairability of the hydrogel. A detailed in vivo comparative study with a commercially available DuoDERM® gel revealed that SAP hydrogel not only promoted wound closure but also showed better deposition and remodeling of the extracellular matrix. Moreover, the hydrogel also demonstrated its ability to downregulate pro-inflammatory markers (IL-1ß, TNF-α) and upregulation of anti-inflammatory markers (IL-10, TGF-ß) at the early stage of healing. Therefore, the bioactive proteins-carbohydrates composite efficiently accelerates skin regeneration and possesses great translational potential to offer a low-cost alternative wound care therapeutic.

Harnessing Multifaceted Next-Generation Technologies for Improved Skin Wound Healing.

Dysregulation of sequential and synchronized events of skin regeneration often results in the impairment of chronic wounds. Conventional wound dressings fail to trigger the normal healing mechanism owing to the pathophysiological conditions. Tissue engineering approaches that deal with the fabrication of dressings using various biomaterials, growth factors, and stem cells have shown accelerated healing outcomes. However, most of these technologies are associated with difficulties in scalability and cost-effectiveness of the products. In this review, we survey the latest developments in wound healing strategies that have recently emerged through the multidisciplinary approaches of bioengineering, nanotechnology, 3D bioprinting, and similar cutting-edge technologies to overcome the limitations of conventional therapies. We also focus on the potential of wearable technology that supports complete monitoring of the changes occurring in the wound microenvironment. In addition, we review the role of advanced devices that can precisely enable the delivery of nanotherapeutics, oligonucleotides, and external stimuli in a controlled manner. These technological advancements offer the opportunity to actively influence the regeneration process to benefit the treatment regime further. Finally, the clinical relevance, trajectory, and prospects of this field have been discussed in brief that highlights their potential in providing a beneficial wound care solution at an affordable cost.