Recent advances in bioprinting technology have been used to precisely dispense cell-laden biomaterials for the construction of complex 3D functional living tissues or artificial organs. Organ printing and biofabrication provides great potential for the freeform fabrication of 3D living organs using cellular spheroids, biocomposite nanofibers, or bioinks as building blocks for regenerative therapy. Vascularization is often identified as a main technological barrier for building 3D organs in tissue engineering. 3D printing of living tissues starts with potential support of biomaterials to maintain structural integrity and degradation of certain time periods after printing of the scaffolds. Biofabrication is the production of complex living and nonliving biological products from raw materials such as cells, molecules, ECM, and biomaterials. Generally, two basic methods are used for the fabrication of scaffolds such as conventional/traditional fabrication processes and advance fabrication processes for engineering organs. A wide range of polymers and biomaterials are used for the fabrication of scaffolds in tissue engineering applications. 3D additive manufacturing is advancing day-by-day; however, there are various critical challenging factors used for fabricating 3D scaffolds. This review is aimed at understanding the various scaffold fabrication techniques, types of polymers and biomaterials used for the fabrication processes, various fields of applications, and different challenges faced in their fabrication of scaffolds in regenerative therapy.

Diabetes mellitus (DM) is a common endocrine disease characterized by a state of hyperglycemia (higher level of glucose in the blood than usual). DM and its complications can lead to diabetic foot ulcer (DFU). DFU is associated with impaired wound healing, due to inappropriate cellular and cytokines response, infection, poor vascularization, and neuropathy. Effective therapeutic strategies for the management of impaired wound could be attained through a better insight of molecular mechanism and pathophysiology of diabetic wound healing. Nanotherapeutics-based agents engineered within 1–100 nm levels, which include nanoparticles and nanoscaffolds, are recent promising treatment strategies for accelerating diabetic wound healing. Nanoparticles are smaller in size and have high surface area to volume ratio that increases the likelihood of biological interaction and penetration at wound site. They are ideal for topical delivery of drugs in a sustained manner, eliciting cell-to-cell interactions, cell proliferation, vascularization, cell signaling, and elaboration of biomolecules necessary for effective wound healing. Furthermore, nanoparticles have the ability to deliver one or more therapeutic drug molecules, such as growth factors, nucleic acids, antibiotics, and antioxidants, which can be released in a sustained manner within the target tissue. This review focuses on recent approaches in the development of nanoparticle-based therapeutics for enhancing diabetic wound healing.

Electrospun fibers have emerged as promising materials in the field of biomedicine, due to their superior physical and cell supportive properties. In particular, electrospun mats are being developed for advanced wound dressing applications. Such applications require the firers to possess excellent antimicrobial properties in order to inhibit potential microbial colonization from resident and non-resident bacteria. In this study, we have developed Poly-ε-Caprolactone /gelatin hybrid composite mats loaded with natural herbal extract (Gymnema sylvestre) to prevent bacterial colonization. As-spun scaffolds exhibited good wettability and desirable mechanical properties retaining their fibrous structure after immersing them in phosphate buffered saline (pH 7.2) for up to 30 days. The initial burst release of Gymnema sylvestre prevented the colonization of bacteria as confirmed by the radial disc diffusion assay. Furthermore, the electrospun mats promoted cellular attachment, spreading and proliferation of human primary dermal fibroblasts and cultured keratinocytes, which are crucial parenchymal cell-types involved in the skin recovery process. Overall these results demonstrated the utility of Gymnema sylvestre impregnated electrospun PCL/Gelatin nanofibrous mats as an effective antimicrobial wound dressing.

Aloe vera (AV) and tetracycline hydrochloride (TCH) exhibit significant properties such as anti-inflammatory, antioxidant and anti-bacterial activities to facilitate skin tissue engineering. The present study aims to develop poly-ε-caprolactone (PCL)/ AV containing curcumin (CUR), and TCH loaded hybrid nanofibrous scaffolds to validate the synergistic effect on the fibroblast proliferation and antimicrobial activity against Gram-positive and Gram-negative bacteria for wound healing. PCL/AV, PCL/CUR, PCL/AV/CUR and PCL/AV/TCH hybrid nanofibrous mats were fabricated using an electrospinning technique and were characterized for surface morphology, the successful incorporation of active compounds, hydrophilicity and the mechanical property of nanofibers. SEM revealed that there was a decrease in the fiber diameter (ranging from 360 to 770 nm) upon the addition of AV, CUR and TCH in PCL nanofibers, which were randomly oriented with bead free morphology. FTIR spectra of various electrospun samples confirmed the successful incorporation of AV, CUR and TCH into the PCL nanofibers. The fabricated nanofibrous scaffolds possessed mechanical properties within the range of human skin. The biocompatibility of electrospun nanofibrous scaffolds were evaluated on primary human dermal fibroblasts (hDF) by MTS assay, CMFDA, Sirius red and F-actin stainings. The results showed that the fabricated PCL/AV/CUR and PCL/AV/TCH nanofibrous scaffolds were non-toxic and had the potential for wound healing applications. The disc diffusion assay confirmed that the electrospun nanofibrous scaffolds possessed antibacterial activity and provided an effective wound dressing for skin tissue engineering.

Burn wounds are susceptible to microbial invasion from both resident and exogenous bacteria, which becomes a critical public health issue and causes substantial economic burden. There is a perceived demand to produce new antimicrobial wound dressings that hinder bacterial colonization while accelerating the healing process and hence would provide an improved standard of care for patients. Since ancient times, herbal extracts from medicinally important plants have extensively been used for treating burn injuries. This work reports the utility of electrospun nanofibers containing plant extracts and antibiotics combination as a multifunctional scaffold for treating second-degree burns. First, we determined the various components of plant extracts from Gymnema sylvestre by two different processing methods and their synergism with minocycline antibiotics. Then, we prepared core− shell nanofibrous dressings with poly-ε-caprolactone/gelatin laden with minocycline hydrochloride as a shell and gelatin infused with G. sylvestre extracts (ultrasound-assisted extracts and cold macerated extracts) as the core using coaxial electrospinning. The electrospun nanofibers displayed a smooth, continuous, and bead-free morphology with adequate wettability. The presence of extract components in the core−shell nanofibers resulted in enhanced mechanical properties when compared to pristine mats. The core− shell structures resulted in sustained release of the bioactive components when compared to nanofiber blends. Core−shell nanofiber mats containing plant extracts and antibiotic combinations displayed potent antimicrobial and antibiofilm properties while promoting the spread and proliferation of skin cells when compared to pristine mats. In a porcine model of cutaneous second-degree burns, we showed that wounds treated with the antimicrobial dressing improved re-epithelialization and collagen organization in comparison to untreated wounds.