Coronavirus disease 2019 (COVID-19) was first identified in an outbreak in Wuhan, China, on December 8, 2019. Globally, the number of patients affected with COVID-19 is growing exponentially, with the death toll exceeding 27,300 as of March 27, 2020. Worldwide, there is a limited supply of N95 respirator masks, face shields, ventilator valves, testing kits, and other personal protective equipment (PPE). 1,2 Thus, adequate production and distribution of PPE is critical during this pandemic. To address these shortages, three-dimensional (3D) printing, a novel and innovative technology used to fabricate complex architectures, is well suited. Three-dimensional printing is an adjustable, robotic platform allowing for tailored deposition of biomaterials using computer-aided design (CAD) systems to formulate layer-by-layer custom designs with controlled architecture and composition. [3][4][5][6][7] Funding: None.

Bone defects resulting from trauma or infection need timely and effective treatments to restore damaged bone. Using specialized three-dimensional (3-D) printing technology we have created custom 3-D scaffolds of hydroxyapatite (HA)/Beta-Tri-Calcium Phosphate (β-TCP) to promote bone repair. To further enhance bone regeneration we have coated the scaffolds with dipyridamole, an agent that increases local adenosine levels by blocking cellular uptake of adenosine. 15% HA:85% β-TCP scaffolds were designed using Robocad software, fabricated using a 3-D Robocasting system, and sintered at 1100°C for 4h. Scaffolds were coated with BMP-2 (200ng/ml), Dypiridamole 100µM or saline and implanted in C57B6 and adenosine A2A receptor knockout (A2AKO) mice with 3mm cranial critical bone defects for 2-8 weeks. Dipyridamole release from scaffold was assayed spectrophotometrically. MicroCT and histological analysis were performed. micro-computed tomography (microCT) showed significant bone formation and remodeling in HA/β-TCP- dipyridamole and HA/β-TCP -BMP-2 scaffolds when compared to scaffolds immersed in vehicle at 2, 4 and 8 weeks (n=5 per group; p≤ 0.05, p≤ 0.05 and p≤ 0.01, respectively). Histological analysis showed increased bone formation and a trend toward increased remodeling in HA/β-TCP- dipyridamole and HA/β-TCP-BMP-2 scaffolds. coating scaffolds with dipyridamole did not enhance bone regeneration in A2AKO mice. In conclusion, scaffolds printed with HA/β-TCP promote bone regeneration in critical bone defects and coating these scaffolds with agents that stimulate A2A receptors and growth factors can further enhance bone regeneration. These coated scaffolds may be very useful for treating critical bone defects due to trauma, infection or other causes.

BACKGROUND Tissue engineering is used to fabricate 3-dimensional (3D) artificial scaffolds to create a microenvironment that mimics human tissue. Bioprinting uses biomaterials, cells, and/or bioink to fabricate prospective scaffolds to mirror the structural, compositional, and functional aspects of the skin. Various bioprinting methods (inkjet-based bioprinting, pressure-assisted bioprinting, and laser-assisted bioprinting) have been used for regenerative wound repair and have been characterized based on biocompatibility, cellular microenvironment, cell proliferation, vitality, and morphology. OBJECTIVE This article reviews the basic principles of 3D printing, current 3D skin bioprinting applications and approaches, and future directions for regenerative medical skin constructs. METHODS A comprehensive literature review was conducted using PubMed with keywords “three-dimensional printing,” “dermatologic surgery,” “bioprinting,” “reconstructive surgical procedures,” “wound healing,” “skin grafts,” “skin scaffolds,” “tissue reconstruction,” and “tissue engineering.” RESULTS A summary of the different applications and 3-dimensional skin bioprinting techniques is presented. In addition, synthetic, natural, and combination polymers are reviewed. Advantages, disadvantages, indications, and approaches are discussed in depth. CONCLUSION Skin grafting is a dynamic technique of dermal reconstruction that can be successful with comprehensive knowledge of skin bioprinting methods.

Exogenous ochronosis is a potential side effect associated with hydroquinone, and treatment is often unsatisfactory. Our study objectives were to review data on hydroquinone-associated ochronosis to determine risk factors for patients experiencing this adverse event. On September 27, 2020 (MEDLINE/PubMed), and October 30, 2020 (Scopus and Web of Science), databases were searched for "ochronosis + hydroquinone" by both authors to reduce risk basis. PRISMA reporting guidelines were used to select 56 articles with a total of 126 patients with hydroquinone-associated ochronosis. Included articles described hydroquinone-associated ochronosis. Articles were excluded if they had irrelevant content, were non-English language text, and were non-case studies. Full text articles were assessed and recorded. Cross-tabulation analysis was performed on categorical data, and Fisher exact test was performed. Ochronosis was most often reported in middle-aged women (53.2%), of African descent (45.2%), Black races (55.5%), and Fitzpatrick skin types V-VI (52.4%). It was most frequently reported with unknown and hydroquinone concentrations greater than 4% (32.5 and 35.7% cases, respectively). Median duration of use was 5 years, with only four cases reported with courses 3 months or shorter and eight cases reported with use 1 year or less. All patients presented with facial blue-black or gray-blue macules in a reticulate, lacelike fashion. Histopathology consistently showed solar elastosis and brownish-yellow, 'banana-shaped' fibers between degenerated collagen fibers of the papillary dermis. Based on these findings, we conclude that hydroquinone in concentrations above 4% and in treatment courses longer than 3 months may be associated with new-onset ochronosis.

Severe acute respiratory syndrome coronavirus 2 has infected over 109 000 000 people with 2 423 443 deaths as of February 17, 2021. Currently, there are no approved or consistently effective treatments, and conventional vaccines may take several years for development and testing. In silico methods of bioinformatics, vaccinogenomics, immunoinformatics, structural biology, and molecular simulations can be used for more rapid and precise vaccine design. This paper highlights two major immunoinformatics strategies that are used in designing novel and effective vaccines and therapeutics: reverse vaccinology and structural vaccinology.