A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D) scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

Polymers derived from plant (polysaccharides) and animal (proteins) kingdoms have been widely used for a variety of biomedical applications including drug delivery and tissue regeneration. These polymers due to their biochemical similarity with human extracellular matrix components are readily recognized and accepted by the body. Natural polymers inherit numerous advantages including natural abundance, relative ease of isolation, and room for chemical modification to meet varying technological needs. In addition, these polymers undergo enzymatic and/or hydrolytic degradation in biologic environments into non-toxic degradation byproducts. Polysaccharides (carbohydrates) are often isolated and purified from renewable sources including plants, animals, and microorganisms. Majority of these polymers are found in the extracellular matrix components of organisms and participate in inter and intracellular cell signaling and contribute to their growth. All these features offer polysaccharide-based biomaterials much desired biological recognition, biocompatibility, and bioactivity. In spite of many merits as biomaterials, these polysaccharides suffer from drawbacks including variations in material properties based on source, microbial contamination, uncontrolled water uptake, poor mechanical strength, and unpredictable degradation patterns. These inconsistencies have limited the usage of polysaccharides and biomedical application related technology development. Many of these polysaccharides have been chemically modified to achieve consistent physicochemical properties including mechanical stability, degradation, and bioactivity and processed into microparticles, hydrogels, and 3D porous structures for tissue regeneration applications. Presence of multiple functionalities on the polymer backbone allows easy structure modifications for the required application. The current article focuses on the application of polysaccharide-based materials in regenerative engineering and delivery.

The HIV/AIDS pandemic and its impact on women prompt the investigation of prevention strategies to interrupt sexual transmission of HIV. Long-acting drug delivery systems that simultaneously protect womenfrom sexual transmission of HIV and unwanted pregnancy could be important tools in combating the pandemic. We describe the design, in silico, in vitro and in vivo evaluation of a dual-reservoir intravaginal ring that delivers the HIV-1 reverse transcriptase inhibitor tenofovir and the contraceptive levonorgestrel for 90 days. Two polyether urethanes with two different hard segment volume fractions were used to make coaxial extruded reservoir segments with a 100 µm thick rate controlling membrane and a diameter of 5.5 mm that contain 1.3 wt% levonorgestrel. A new mechanistic diffusion model accurately described the levonorgestrel burst release in early time points and pseudo-steady state behavior at later time points. As previously described, tenofovir was formulated as a glycerol paste and filled into a hydrophilic polyurethane, hollow tube reservoir that was melt-sealed by induction welding. These tenofovir-eluting segments and 2 cm long coaxially extruded levonorgestrel eluting segments were joined by induction welding to form rings that released an average of 7.5 mg tenofovir and 21 µg levonorgestrel per day in vitro for 90 days. Levonorgestrel segments placed intravaginally in rabbits resulted in sustained, dose-dependent levels of levonorgestrel in plasma and cervical tissue for 90 days. Polyurethane caps placed between segments successfully prevented diffusion of levonorgestrel into the tenofovir-releasing segment during storage.Hydrated rings endured between 152 N and 354 N tensile load before failure during uniaxial extension testing. In summary, this system represents a significant advance in vaginal drug delivery technology, and is the first in a new class of long-acting multipurpose prevention drug delivery systems.

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