3D Printed Bioactive PLGA Dermal Scaffold for Burn Wound Treatment.

Burn injury represents a major global public healthcare problem and has a significant health-economics impact. In this study, we report on a 3D printed poly(lactic-co-glycolic acid) (PLGA) dermal scaffold containing bioactive PLGA for burn wound healing. Bioactive brush copolymers containing pendant side chains of PLGA and PEGylated Arg-Gly-Asp tripeptide (RGD) or hyaluronic acid (HA) were synthesized by ring-opening metathesis polymerization (ROMP). These copolymers exhibited good thermal stability for material processing using melt-extrusion-based methods. The copolymers were blended with commercial PLGA, extruded into filaments and 3D printed using fused filament fabrication (FFF) methods with incorporated porosities. The 3D printed scaffolds demonstrated good biocompatibility in in vitro cell assays and in vivo murine models. Porcine study based on partial thickness burn wound model showed that these PLGA scaffolds facilitated re-epithelization with reduced inflammation as compared to the clinical gold standard for second-degree burn wound treatment, Biobrane. The bioactive PLGA scaffolds presented herein are beneficial in wound healing and have therapeutic potential in burn wounds treatment.

Bioactive PCL-Peptide and PLA-Peptide Brush Copolymers for Bone Tissue Engineering.

We report the modular synthesis of bioactive brush-type polycaprolactone-peptide and polylactide-peptide copolymers for applications in bone tissue engineering. The brush copolymers containing pendant side chains of polycaprolactone (PCL) or polylactide (PLA) and PEGylated peptides, including linear Arg-Gly-Asp and collagen-like peptide (Gly-Pro-Hyp)3, were synthesized by ring-opening metathesis polymerization with high conversions and low dispersities (<1.5). These PCL-peptide and PLA-peptide copolymers exhibited good thermal stability for material processing using melt-extrusion-based methods. The copolymers were blended with commercial PCL or PLA, extruded into filaments, and 3D printed using fused filament fabrication methods. These bioactive PCL and PLA materials promoted osteogenic differentiation in vitro and showed good biocompatibility in in vivo murine model study. The promising results presented herein will serve as a useful guide for the design and functionalization of PCL or PLA materials for use in bone tissue engineering.

Machine Learning-Driven Biomaterials Evolution.

Biomaterials is an exciting and dynamic field, which uses a collection of diverse materials to achieve desired biological responses. While there is constant evolution and innovation in materials with time, biomaterials research has been hampered by the relatively long development period required. In recent years, driven by the need to accelerate materials development, the applications of machine learning in materials science has progressed in leaps and bounds. The combination of machine learning with high-throughput theoretical predictions and high-throughput experiments (HTE) has shifted the traditional Edisonian (trial and error) paradigm to a data-driven paradigm. In this review, each type of biomaterial and their key properties and use cases are systematically discussed, followed by how machine learning can be applied in the development and design process. The discussions are classified according to various types of materials used including polymers, metals, ceramics, and nanomaterials, and implants using additive manufacturing. Last, the current gaps and potential of machine learning to further aid biomaterials discovery and application are also discussed.

Biomaterials by design: Harnessing data for future development.

Biomaterials is an interdisciplinary field of research to achieve desired biological responses from new materials, regardless of material type. There have been many exciting innovations in this discipline, but commercialization suffers from a lengthy discovery to product pipeline, with many failures along the way. Success can be greatly accelerated by harnessing machine learning techniques to comb through large amounts of data. There are many potential benefits of moving from an unstructured empirical approach to a development strategy that is entrenched in data. Here, we discuss the recent work on the use of machine learning in the discovery and design of biomaterials, including new polymeric, metallic, ceramics, and nanomaterials, and how machine learning can interface with emerging use cases of 3D printing. We discuss the steps for closer integration of machine learning to make this exciting possibility a reality.

Anti-Markovnikov oxidation and hydration of terminal olefins.

Efficient syntheses of aldehydes and primary alcohols from terminal olefins are critical to the chemical laboratory and industry. Heavy emphasis has been placed on regioselective olefin functionalization in recent decades. This perspective mainly focuses on advances in the Wacker-type oxidation and tandem hydration of terminal olefins with anti-Markovnikov selectivity.

Formal hydration of non-activated terminal olefins using tandem catalysts.

The hydration of terminal olefins to secondary alcohols has been achieved using a Pd(II)/Ru(II) catalyst combination with high regioselectivity and yields. Both vinyl arenes and aliphatic olefins can be hydrated easily with the tandem catalyst system using a low catalyst loading of 1 mol%.

Efficient and highly aldehyde selective Wacker oxidation.

A method for efficient and aldehyde-selective Wacker oxidation of aryl-substituted olefins using PdCl(2)(MeCN)(2), 1,4-benzoquinone, and t-BuOH in air is described. Up to a 96% yield of aldehyde can be obtained, and up to 99% selectivity can be achieved with styrene-related substrates.

Primary alcohols from terminal olefins: formal anti-Markovnikov hydration via triple relay catalysis.

Alcohol synthesis is critical to the chemical and pharmaceutical industries. The addition of water across olefins to form primary alcohols (anti-Markovnikov olefin hydration) would be a broadly useful reaction but has largely proven elusive; an indirect hydroboration/oxidation sequence requiring stoichiometric borane and oxidant is currently the most practical methodology. Here, we report a more direct approach with the use of a triple relay catalysis system that couples palladium-catalyzed oxidation, acid-catalyzed hydrolysis, and ruthenium-catalyzed reduction cycles. Aryl-substituted terminal olefins are converted to primary alcohols by net reaction with water in good yield and excellent regioselectivity.

Synthesis, characterization, and single-molecule metamagnetism of new Co(II) polynuclear complexes of pyridine-2-ylmethanol.

The reaction between pyridine-2-ylmethanol (HL), anhydrous CoCl(2) and NaH afforded polynuclear Co(II) complexes [Co(7)(L)(12)]Cl(2) (1), [Co(6)Na(L)(12)]Cl (2) and [Co(4)Cl(2)(L)(6)] (3), depending on the HL:CoCl(2) ratio set in the reaction. The core structures of the centrosymmetric complexes 1 and 2 are of the M@Co(6) type (M = Co or Na, respectively) with a coplanar arrangement of the metals whereas that of centrosymmetric 3 is of an incomplete dicubane type. The experimental conditions allowing interconversions between these polynuclear complexes have been determined, which provides a more rational control of their synthesis. Thus, 1 transforms to 3 when reacted with CoCl(2) in a 1 : 1 ratio, whereas the same reaction performed with a large excess of CoCl(2) gave the tetranuclear pseudo-cubane complex [Co(4)(L)(4)Cl(2)(MeOH)(4)] upon recrystallization. Conversely, 1 was isolated from the reaction of 3 with HL and NaH. The crystal structure of these compounds is reported, along with the magnetic behaviour of 1 and 3. The analysis of the magnetism using the effective spin-1/2 Hamiltonian approach revealed single-molecule metamagnetic behavior in 3.

Isolation of cationic digold-frame with free carboxylic acid pendants.

Use of different diphosphines enables the isolation and crystallographic characterization of gold pyridylcarboxylate complexes with different structural motifs. Dppm [bis(diphenylphosphino)methane] supports side-by-side-like complexes [Au(2)(dppm)(IsonicH)(2)](2+) (isonicH = 4-NC(5)H(4)CO(2)H) with aurophilic and pipi interactions of the pyridyl rings. Use of dppen [1,2-bis(diphenylphosphino)ethylene] removes the latter interaction but keeps the orthogonal closed-shell interaction of Au(I) in [Au(2)(dppen)(IsonicH)(2)](2+). The ligand dppe [1,2-bis(diphenylphosphino)ethane] helps to push the gold centers apart in [Au(2)(dppe)(isonicH)(2)](2+) and remove both interactions. These digold complexes are potential metalloligands that carry functional acids which can be conveniently activated by deprotonation.

Na+ and Ca2+ ion selective pyridylcarboxylate rings of Pd(II) and Pt(II).

A series of dinuclear Pd(II) and Pt(II) with central rectangular cavities have been self-assembled using pyridyl carboxylates as spacers and phosphines [1,1'-bis(diphenylphosphino)ferrocene (dppf) and triphenylphosphines] as supporting ligands. Some of these function as metallacrowns by capturing adventitious alkali or alkali earth metals ions. Two of the Pt(II) rings bind selectively to Na(+) whereas the Pd(II) rings prefer Ca(2+). Such endocyclic association with the metal ion is facilitated by the converging carbonyl pendants and supported by coordinated triflates. Affinity and selectivity are achieved through stereo-conformational control of the pendant carbonyls and the ring which are isomerically dependent on the spacer. These intermetallic complexes are characterized by X-ray single-crystal crystallography and solution spectroscopy (NMR and ESI-MS). A varied range of local geometries of Na(+) and Ca(2+) are revealed.

Spacer-directed coordination polymers-of-oligomers (POLO) of silver.

A novel series of Ag(I) polymers-of-oligomers with pyridylcarboxylate spacers supported by a diphosphine [1,1'-bis(diphenylphosphino)methane (dppm) or 1,1'-bis(diphenylphosphino)ferrocene (dppf)] has been constructed and crystallographically established. The repeating oligomeric Ag5 block is invariably made up of five Ag(I) centers comprising Ag2 and Ag units with different metal geometries. Other related Ag5 and Ag4 assemblies have also been isolated. The preparation of the [Ag2(isonic)(dppm)2]n(n+) polymer (isonic = 4-pyridyl formate, NC5H4CO2(-)) using a ligand transfer pathway from NiCl2(dppm) to AgOTf (OTf = CF3SO3(-)) has been identified. The structural outcomes suggested that pyridylcarboxylates of different stereogeometrical and conformational properties can stabilize different oligomeric and topological forms through adaptation to the contrasting demands of the diphosphine and metal.

Oligo- and polymeric Pd(II) and Pt(II) using pyridyl carboxylate spacers for topology control.

An array of Pd(II) and Pt(II) supramolecular assemblies have been constructed using pyridyl carboxylates as spacers and phosphines [(C5H4PPh2)2Fe (dppf) and PPh3)] as supporting ligands. Different molecular topologies such as squares, triangles, rectangles, and polymers can be controlled by the spatial and directional character of the spacer. A change of the denticity of the phosphine does not affect the topological outcome. Significant differences, however, are observed for the congeneric analogues, with Pd(II) showing a more pronounced tendency toward coordination polymer formation and its attached carboxyl a higher affinity toward Ag(+). The ability of these assemblies to capture cations, such as Na(+) in [Pt3Na(3-NC5H4CO2)3(OTf)3(PPh3)6](+) through hydrogen bonding or Ag(+) in [PdAg(2-NC5H4CO2)(OTf)2(dppf)] through dative bonding, is described and compared. All of the complexes are structurally characterized by single-crystal X-ray crystallography.

Assembly of gold rings and chains with pyridyl carboxylate as directional spacer.

The combinative use of Au(I), a skeletally flexible diphosphine and a bifunctional spacer of pyridyl carboxylate with tunable directional and donor properties has resulted in a series of structurally distinctive ensembles and Au(2) metalloligands with O-donicity.

General formation of trigonal-prismatic [Ag6X5(dppf)3]+ (X = Cl, Br, I) through an unusual ligand migration from NiX2(dppf) to AgOTf.

Use of NiX2(dppf) (X = Cl, Br, I) as a ligand transfer reagent to AgOTf results in the trigonal prismatic [Ag6X5(dppf)3]OTf complexes. Similar reactions with the dppe analogues give at least 4 different types of dppe-bridged coordinationpolymers.

Constructing homo- and hetero-metallic molecular topologies using pyridylcarboxylates as spacers: preparation of a half-ring complex with active coordination sites.

Addition of isonicotinic acid NC(5)H(4)CO(2)H (or isonicH) to [Pt(dppf)(MeCN)(2)](2+)2OTf(-)(dppf = 1,1'-bis(diphenylphosphino)ferrocene, OTf = triflate) affords a mixture of the homometallic molecular square [Pt(4)(dppf)(4)(mu-O(2)CC(5)H(4)N)(4)](4+)4OTf(-), 1 and its precursor intermediate [Pt(dppf)(eta(1)-NC(5)H(4)CO(2)H)(2)](2+)2OTf(-), 2. The latter captures [Pd(dppf)(MeCN)(2)](2+)2OTf(-) to give a heterometallic square, [Pt(2)Pd(2)(dppf)(4)(mu-O(2)CC(5)H(4)N)(4)](4+)4OTf(-), 3. Slight skeletal modification of the ligand leads to different assemblies. This is illustrated by the addition of NC(5)H(4)CH(2)CO(2)H.HCl to [Pt(dppf)(MeCN)(2)](2+)2OTf(-) to give [PtCl(dppf)(NC(5)H(4)CH(2)CO(2)H)](+)OTf(-), 4, which reacts with another equivalent of AgOTf to yield the dibridged complex [Pt(2)(dppf)(2)(mu-NC(5)H(4)CH(2)CO(2))(2)](2+)2OTf(-), 5. All complexes, with the exception of , have been structurally characterized by single-crystal X-ray crystallography. Complexes 2 and 4 are potential precursors to further molecular topologies.

Unusual coordination assemblies from platinum(II) thienyl and bithienyl complexes.

Dinuclear Pt(2)Br(2)(dppf)(2)(mu-C(8)H(4)S(2)) exchanges with isonicotinic acid to release free bithiophene and gives a molecular square [Pt(4)(dppf)(4)(mu(2)-O(2)CC(5)H(4)N)(4)](4+)4OTf(-) which is an "all-ring" system with four Pt rings disposed at the corners of a larger macrocyclic ring. The related mononuclear complex PtBr(eta(1)(C2)-C(4)H(3)S)(dppf) reacts with AgOTf (OTf = triflate) to give [Pt(2)(dppf)(2)(mu(2),eta(1)(C),eta(1)(S)-C(4)H(3)S)(2)](2+)2OTf(-) with an unusual six-membered ring formed by the fusion of two Pt-thienyl entities at the sulfur sites. All the complexes are structurally characterized by single-crystal X-ray crystallography.