The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that “fits-all” cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications.

Background:The microfracture technique for cartilage repair has limited ability to regenerate hyaline cartilage. Aim: The current study made a direct comparison between microfracture and an osteochondral approach with microsphere-based gradient plugs. Materials & methods: The PLGA-based scaffolds had opposing gradients of chondroitin sulfate and β-tricalcium phosphate. A 1-year repair study in sheep was conducted. Results: The repair tissues in the microfracture were mostly fibrous and had scattered fissures with degenerative changes. Cartilage regenerated with the gradient plugs had equal or superior mechanical properties; had lacunated cells and stable matrix as in hyaline cartilage. Conclusion: This first report of gradient scaffolds in a long-term, large animal, osteochondral defect demonstrated potential for equal or better cartilage repair than microfracture.

The process of wound healing includes four phases: Hemostasis, inflammation, proliferation, and remodeling. Many wound dressings and technologies have been developed to enhance the body's ability to close wounds and restore the function of damaged tissues. Several advancements in wound healing technology have resulted from innovative experiments by individual scientists or physicians working independently. The interplay between the medical and scientific research fields is vital to translating new discoveries in the lab to treatments at the bedside. Tracing the history of wound dressing development reveals that there is an opportunity for deeper collaboration between multiple disciplines to accelerate the advancement of novel wound healing technologies. In this review, we explore the different types of wound dressings and biomaterials used to treat wounds, and we investigate the role of multidisciplinary collaboration in the development of various wound management technologies to illustrate the benefit of direct collaboration between physicians and scientists. K E Y W O R D Sbiomedical engineering, interdisciplinary teams, negative pressure wound therapy, wound dressings, wound healing | INTRODUCTIONA glossary of terms found in the introduction is provided in Table 1. | Overview of wound healingWound healing involves four phases: Hemostasis, inflammation, proliferation, and remodeling. 1 Wound healing begins with transient vasoconstriction of injured vessels. 2 In the initial phase, damage to the skin exposes the subendothelial collagen and tissue factor, leading to platelet aggregation. 3 In this process, Von Willebrand factor (vWF) binds to both the subendothelial collagen and the platelet receptor glycoprotein Ib/IX/V. 4 This adhesion, as well as thrombin generated by tissue factor, results in platelet activation, degranulation, and conformational change. 5 Conformational change in glycoprotein IIB/IIIA allows the binding of fibrinogen, a crucial step in platelet aggregation and formation of the platelet plug. Tissue factor and phosphatidylserine, located on the surface of platelets and endothelial cells, form a complex with circulating activated Factor VII, leading to activation of a coagulation cascade which results in the cleavage of fibrinogen to fibrin. 5 Fibrin activates Factor XIII, which acts to crosslink the fibrin monomers. The final result is a strong blood clot. 6

Wound healing is a dynamic series of interconnected events with the ultimate goal of promoting neotissue formation and restoration of anatomical function. Yet, the complexity of wound healing can often result in development of complex, chronic wounds, which currently results in a significant strain and burden to our healthcare system. The advancement of new and effective wound care therapies remains a critical issue, with the current therapeutic modalities often remaining inadequate. Notably, the field of tissue engineering has grown significantly in the last several years, in part, due to the diverse properties and applications of polymeric biomaterials. The interdisciplinary cohesion of the chemical, biological, physical, and material sciences is pertinent to advancing our current understanding of biomaterials and generating new wound care modalities. However, there is still room for closing the gap between the clinical and material science realms in order to more effectively develop novel wound care therapies that aid in the treatment of complex wounds. Thus, in this review, we discuss key material science principles in the context of polymeric biomaterials, provide a clinical breadth to discuss how these properties affect wound dressing design, and the role of polymeric biomaterials in the innovation and design of the next generation of wound dressings.

Negative pressure wound therapy has greatly advanced the field of wound healing for nearly two decades, by providing a robust surgical adjunct technique for accelerating wound closure in acute and chronic wounds. However, the application of negative pressure wound therapy in maxillofacial applications has been relatively under utilized as a result of the physical articulations and contours of the head and neck that make it challenging to obtain an airtight seal for different negative pressure wound therapy systems. Adapting negative pressure wound therapies for maxillofacial applications could yield significant enhancement of wound closure in maxillofacial applications. The current review summarizes the basic science underlying negative pressure wound therapy, as well as specific maxillofacial procedures that could benefit from negative pressure wound therapy.

Aim: To compare the physiological behavior of mesenchymal stem/stromal cells (MSCs) within an expandable tissue-mimetic 3D system relative to in vitro expansion in a traditional 2D system. Methods: Adipose-derived MSCs (ASCs) were continuously cultured for 6 weeks on either 2D culture plastic or in a 3D hydrogel system that eliminated subculturing. ASCs were assessed for senescence, ‘stem-like’ MSC markers, and ability for their secretome to augment a secondary cell population. Results: The 3D hydrogel system resulted in an enhanced retention of more regenerative, nonsenescent ASC populations that exhibited increased expression of ‘stem-like’ MSC surface markers. Conclusion: This study introduces a proof-of-concept design for a novel modular 3D system that can improve in vitro expansion of stem-like cell populations for future regenerative therapies.

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Hydrogels can be fabricated and designed to exert direct control over stem cells' adhesion and differentiation. In this study, we have investigated the use of polydopamine (pDA)‐treatment as a binding platform for bioactive compounds to create a versatile gelatin–alginate (Gel–Alg) hydrogel for tissue engineering applications. Precisely, pDA was used to modify the surface properties of the hydrogel and better control the adhesion and osteogenic differentiation of human adipose‐derived stem cells (hASCs). pDA enabled the adsorption of different types of bioactive molecules, including a model osteoinductive drug (dexamethasone) as well as a model pro‐angiogenic peptide (QK). The pDA treatment efficiently retained the drug and the peptide compared to the untreated hydrogel and proved to be effective in controlling the morphology, cell area, and osteogenic differentiation of hASCs. Overall, the findings of this study confirm the efficacy of pDA treatment as a valuable strategy to modulate the biological properties of biocompatible Gel–Alg hydrogels and further extend their value in regenerative medicine.