Tissue Engineering. Part B, Reviews最新文献

Tendon injuries disrupt the transmission of forces from muscle to bone, leading to chronic pain, disability, and a large socioeconomic burden. Tendon injuries are prevalent; there are over 300,000 tendon repair procedures a year in the United States to address acute trauma or chronic tendinopathy. Successful restoration of function after tendon injury remains challenging clinically. Despite improvements in surgical and physical therapy techniques, the high complication rate of tendon repair procedures motivates the use of therapeutic interventions to augment healing. While many biological and tissue engineering approaches have attempted to promote scarless tendon healing, there is currently no standard clinical treatment to improve tendon healing. Moreover, the limited efficacy of systemic delivery of several promising therapeutic candidates highlights the need for tendon-specific drug delivery approaches to facilitate translation. This review article will synthesize the current state-of-the-art methods that have been used for tendon-targeted delivery through both systemic and local treatments, highlight emerging technologies used for tissue-specific drug delivery in other tissue systems, and outline future challenges and opportunities to enhance tendon healing through targeted drug delivery.

Diabetes is a disease that plagues over 463 million people globally. Approximately 40 million of these patients have type 1 diabetes mellitus (T1DM), and the global incidence is increasing by up to 5% per year. T1DM is where the body's immune system attacks the pancreas, specifically the pancreatic beta cells, with antibodies to prevent insulin production. Although current treatments such as exogenous insulin injections have been successful, exorbitant insulin costs and meticulous administration present the need for alternative long-term solutions to glucose dysregulation caused by diabetes. Encapsulated islet transplantation (EIT) is a tissue-engineered solution to diabetes. Donor islets are encapsulated in a semipermeable hydrogel, allowing the diffusion of oxygen, glucose, and insulin but preventing leukocyte infiltration and antibody access to the transplanted cells. Although successful in small animal models, EIT is still far from commercial use owing to necessary long-term systemic immunosuppressants and consistent immune rejection. Most published research has focused on tailoring the characteristics of the capsule material to promote clinical viability. However, most studies have been limited in scope to biochemical changes. Current mechanobiology studies on the effect of substrate stiffness on the function of leukocytes, especially macrophages-primary foreign body response (FBR) orchestrators, show promise in tailoring a favorable response to tissue-engineered therapies such as EIT. In this review, we explore strategies to improve the clinical viability of EIT. A brief overview of the immune system, the FBR, and current biochemical approaches will be elucidated throughout this exploration. Furthermore, an argument for using substrate stiffness as a capsule design parameter to increase EIT efficacy and clinical viability will be posed.

Small-caliber tissue-engineered vascular grafts (TEVGs, luminal diameter <6 mm) are promising therapies for coronary or peripheral artery bypassing surgeries or emergency treatments of vascular trauma, and a robust seed cell source is required for scalable manufacturing of small-caliber TEVGs with robust mechanical strength and bioactive endothelium in future. Human-induced pluripotent stem cells (hiPSCs) could serve as a robust cell source to derive functional vascular seed cells and potentially lead to generation of immunocompatible engineered vascular tissues. Up to date, this rising field of small-caliber hiPSC-derived TEVG (hiPSC-TEVG) research has received increasing attention and achieved significant progress. Implantable, small-caliber, hiPSC-TEVGs have been generated. These hiPSC-TEVGs displayed rupture pressure and suture retention strength approaching to those of human native saphenous veins, with vessel wall decellularized and luminal surface endothelialized with monolayer of hiPSC-endothelial cells. Meanwhile, a series of challenges remain in this field, including functional maturity of hiPSC-derived vascular cells, poor elastogenesis, suboptimal efficiency of obtaining hiPSC-derived seed cells, and relative low ready availability of hiPSC-TEVGs, which are waiting to be addressed. This review is conceived to introduce representative achievements and challenges in small-caliber TEVG generation using hiPSCs, and encapsulate the potential solution and future directions.

To conduct a systematic review of studies reporting the treatment of tendon injury using biomaterials in animal models. A systematic search was conducted to retrieve studies involving animal models of tendon repair using biomaterials, in PubMed (database construction to August 2022) and Ovid-Embase (1946 to August 2022). Data related to tendon repair with biomaterials were extracted by two researchers, respectively. Risk of bias was assessed following the Cochrane Handbook for Systematic Reviews of Interventions. A statistical analysis was performed based on the classification of tendon repair biomaterials included in our study. A total of 8413 articles were retrieved, with 78 studies included in our analysis. For tendon repair in animal models using biomaterials, the most commonly seen characteristics were as follows: naturally derived biomaterials, rabbits and rats as animal models, surgery as the injury model, and the Achilles tendon as the injury site. The histology and biomechanical recovery of tendon injury following repair are affected by different biomaterials. Studies of tendon repair in animal models indicate that biomaterials can significantly improve repair outcomes, including tendon structure and biomechanics. Among effective biomaterial strategies are the use of new composites and incorporation of cells or growth factors into the material, both of which provide obvious benefits for tendon healing. More high-quality preclinical studies are required to encourage the translation of biomaterials into clinical practice for tendon repair.

Surgical outcomes of pelvic organ prolapse (POP) surgery are poor, resulting in a 20% recurrence risk. Following the hypothesis that impaired wound healing is the main determinant of recurrent POP, growth factors have the potential to promote wound healing and may improve surgical outcomes. In this study, we systematically reviewed the effect of growth factors on vaginal wound healing in both in vitro and animal studies. For each independent comparison, the standardized mean difference and 95% CI were calculated using the Hedges' g correction. Of the 3858 retrieved studies, seven studies were included, of which six were included in meta-analysis (three in vitro studies and four in vivo studies). In vitro, basic fibroblast growth factor (bFGF) promotes proliferation, differentiation, and collagen types I and III production. Epidermal growth factor stimulates proliferation and connective tissue growth factor promotes Tenascin-C expression. These effects, however, are less pronounced in vivo; only bFGF slightly promotes collagen production. The review shows that growth factors, particularly bFGF, are able to promote vaginal wound healing in vitro. The uncertain in vivo findings suggest that preclinical models should be improved. The ultimate goal is to develop effective growth factor-supplemented therapies that improve surgical outcomes for POP.

Deferoxamine (DFO) is an iron chelator with FDA approval for the clinical treatment of iron excess. As a well-established stabilizer of hypoxia-inducible factor-1α (HIF-1α), DFO can efficiently upregulate HIF-1α and relevant downstream angiogenic factors, leading to accelerated vascularization. Moreover, as increasing studies have focused on DFO as a hypoxia-mimetic agent in recent years, it has been shown that DFO exhibited multiple functions, including stem cell regulation, immunoregulation, provascularization, and pro-osteogenesis. On the contrary, DFO can bind excess iron ions in wounds of chronic inflammation, while serving as an antioxidant with the characteristic of removing reactive oxygen species. Collectively, these characteristics make DFO a potent modulator in tissue engineering for increasing tissue integration of biomaterials in vivo and facilitating wound healing. This review outlines the activity of DFO as a representative hypoxia-mimetic agent in cells as well as the evolution of its application in tissue engineering. It can be concluded that DFO is a medication with tremendous promise and application value in future trends, which can optimize biomaterials and existing tissue engineering techniques for tissue regeneration.

Articular cartilage is composed of superficial, medial, and deep zones, which endow the tissue with biphasic mechanical properties to withstand shearing force and compressional loading. The tissue has very limited self-healing capacity once it is damaged due to its avascular nature. To prevent the early onset of osteoarthritis, surgical intervention is often needed to repair the injured cartilage. Current noncell-based and cell-based treatments focus on the regeneration of homogeneous cartilage to achieve bulk compressional properties without recapitulating the zonal matrix and mechanical properties, and often oversight in aiding cartilage integration between host and repair cartilage. It is hypothesized that achieving zonal architecture in articular cartilage tissue repair could improve the structural and mechanical integrity and thus the life span of the regenerated tissue. Engineering stratified cartilage constructs using zonal chondrocytes have been hypothesized to improve the functionality and life span of the regenerated tissues. However, stratified articular cartilage repair has yet to be realized to date due to the lack of an efficient zonal chondrocyte isolation method and an expansion platform that would allow both cell propagation and phenotype maintenance. Various attempts and challenges in achieving stratified articular cartilage repair in a clinical setting are evaluated. In this review, different perspectives on achieving stratified articular cartilage repair using zonal chondrocytes are described. The effectiveness of different zonal chondrocyte isolation and zonal chondrocyte phenotype maintenance methodologies during expansion are compared, with the focus on recent advancements in zonal chondrocyte isolation and expansion that could present a possible strategy to overcome the limitation of applying zonal chondrocytes to facilitate zonal architecture development in articular cartilage regeneration. Impact Statement The zonal properties of articular cartilage contribute to the biphasic mechanical properties of the tissues. Recapitulation of the zonal architecture in regenerated articular cartilage has been hypothesized to improve the mechanical integrity and life span of the regenerated tissue. This review provides a comprehensive discussion on the current state of research relevant to achieving stratified articular cartilage repair using zonal chondrocytes from different perspectives. This review further elaborates on a zonal chondrocyte production pipeline that can potentially overcome the current clinical challenges and future work needed to realize stratified zonal chondrocyte implantation in a clinical setting.

Rebuilding the kidney in the context of tissue engineering offers a major challenge as the organ is structurally complex and has a high variety of specific functions. Recreation of kidney function is inherently connected to the formation of tubules since the functional subunit of the kidney, the nephron, is based on tubular structures. In vivo, tubulogenesis culminates in a perfectly shaped, patterned, and functional renal tubule via different morphogenic processes that depend on delicately orchestrated chemical, physical, and mechanical interactions between cells and between cells and their microenvironment. This review summarizes the current understanding of the role of the microenvironment in the morphogenic processes involved in in vivo renal tubulogenesis. We highlight the current state-of-the-art of renal tubular engineering and provide a view on the design elements that can be extracted from these studies. Next, we discuss how computational modeling can aid in specifying and identifying design parameters and provide directions on how these design parameters can be incorporated in biomaterials for the purpose of engineering renal tubulogenesis. Finally, we propose that a step-by-step reciprocal interaction between understanding and engineering is necessary to effectively guide renal tubulogenesis. Impact statement Tubular tissue engineering lies at the foundation of regenerating kidney tissue function, as the functional subunit of the kidney, the nephron, is based on tubular structures. Guiding renal tubulogenesis toward functional renal tubules requires in-depth knowledge of the developmental processes that lead to the formation of native tubules as well as engineering approaches to steer these processes. In this study, we review the role of the microenvironment in the developmental processes that lead to functional renal tubules and give directions how this knowledge can be harnessed for biomaterial-based tubular engineering using computational models.