Regenerative Engineering: Approaches to Limb Regeneration and Other Grand Challenges

Laurencin, Cato T.; Nair, Lakshmi S.

doi:10.1007/s40883-015-0006-z

Cited by 47 publications

(30 citation statements)

References 12 publications

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“…Tissue engineering, in its infancy focused on utilizing biomaterial to improve or restore the diseased tissue [119]. The paradigm of regenerative engineering, an interdisciplinary field, has emerged from the convergence of tissue engineering, advanced materials science, stem cell science, and developmental biology to regenerate damaged complex tissues [120, 121]. Advanced material science provides scaffolds with the right geometry and architecture to provide adequate mechanical support and modulate the cellular activities by sequestering and presenting the chemical and biochemical cues with precise spatial and temporal control.…”

Section: The Principles Of Regenerative Engineeringmentioning

confidence: 99%

Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering

Narayanan

Vernekar

Kuyinu

et al. 2016

Advanced Drug Delivery Reviews

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Regenerative engineering converges tissue engineering, advanced materials science, stem cell science, and developmental biology to regenerate complex tissues such as whole limbs. Regenerative engineering scaffolds provide mechanical support and nanoscale control over architecture, topography, and biochemical cues to influence cellular outcome. In this regard, poly (lactic acid) (PLA)-based biomaterials may be considered as a gold standard for many orthopaedic regenerative engineering applications because of their versatility in fabrication, biodegradability, and compatibility with biomolecules and cells. Here we discuss recent developments in PLA-based biomaterials with respect to processability and current applications in the clinical and research settings for bone, ligament, meniscus, and cartilage regeneration.

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Section: The Principles Of Regenerative Engineeringmentioning

confidence: 99%

Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering

Narayanan

Vernekar

Kuyinu

et al. 2016

Advanced Drug Delivery Reviews

Self Cite

391

240

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“…Biodegradable scaffolds play a crucial role in scaffold based regenerative approach and their successful application is dependent on their inherent properties, and compositions [2, 7, 9, 16, 32, 61, 73, 77]. So far, a large number of polyphosphazene-based polymer systems have been developed for use in bone and soft tissue regeneration, as well as in drug delivery [20, 31, 74, 91, 94, 100, 101].…”

Section: Applications Of Biodegradable Polyphosphazene and Its Blendsmentioning

confidence: 99%

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering

Ogueri

Ivirico

Nair

et al. 2017

Regen. Eng. Transl. Med.

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The occurrence of musculoskeletal tissue injury or disease and the subsequent functional impairment is at an alarming rate. It continues to be one of the most challenging problems in the human health care. Regenerative engineering offers a promising transdisciplinary strategy for tissues regeneration based on the convergence of tissue engineering, advanced materials science, stem cell science, developmental biology and clinical translation. Biomaterials are emerging as extracellular-mimicking matrices designed to provide instructive cues to control cell behavior and ultimately, be applied as therapies to regenerate damaged tissues. Biodegradable polymers constitute an attractive class of biomaterials for the development of scaffolds due to their flexibility in chemistry and the ability to be excreted or resorbed by the body. Herein, the focus will be on biodegradable polyphosphazene-based blend systems. The synthetic flexibility of polyphosphazene, combined with the unique inorganic backbone, has provided a springboard for more research and subsequent development of numerous novel materials that are capable of forming miscible blends with poly (lactide-co-glycolide) (PLAGA). Laurencin and co-workers has demonstrated the exploitation of the synthetic flexibility of Polyphosphazene that will allow the design of novel polymers, which can form miscible blends with PLAGA for biomedical applications. These novel blends, due to their well-tuned biodegradability, and mechanical and biological properties coupled with the buffering capacity of the degradation products, constitute ideal materials for regeneration of various musculoskeletal tissues. Lay Summary Regenerative engineering aims to regenerate complex tissues to address the clinical challenge of organ damage. Tissue engineering has largely focused on the restoration and repair of individual tissues and organs, but over the past 25 years, scientific, engineering, and medical advances have led to the introduction of this new approach which involves the regeneration of complex tissues and biological systems such as a knee or a whole limb. While a number of excellent advanced biomaterials have been developed, the choice of biomaterials, however, has increased over the past years to include polymers that can be designed with a range of mechanical properties, degradation rates, and chemical functionality. The polyphosphazenes are one good example. Their chemical versatility and hydrogen bonding capability encourages blending with other biologically relevant polymers. The further development of Polyphosphazene-based blends will present a wide spectrum of advanced biomaterials that can be used as scaffolds for regenerative engineering and as well as other biomedical applications.

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“…In recent years, the demand for finding alternatives to biological grafts in treating traumatic injuries that involve the loss of multiple tissues has been increasing due to the limited availability of autografts and the need for immunosuppression to allografts 1 . For this reason, there has been a notably growing interest in developing innovative approaches and strategies towards the regeneration of multiple tissue units simultaneously.…”

Section: Robust Phenotypic Maintenance Of Limb Cells During Heterogenmentioning

confidence: 99%

Robust phenotypic maintenance of limb cells during heterogeneous culture in a physiologically relevant polymeric-based constructed graft system

Barajaa

Nair

Laurencin

2020

Sci Rep

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A major challenge during the simultaneous regeneration of multiple tissues is the ability to maintain the phenotypic characteristics of distinct cell populations on one construct, especially in the presence of different exogenous soluble cues such as growth factors. Therefore, in this study, we questioned whether phenotypic maintenance over a distinct population of cells can be achieved by providing biomimetic structural cues relevant to each cell phenotype into the construct’s design and controlling the presentation of growth factors in a region-specific manner. To address this question, we developed a polymeric-based constructed graft system (CGS) as a physiologically relevant model that consists of three combined regions with distinct microstructures and growth factor types. Regions A and B of the CGS exhibited similar microstructures to the skin and soft tissues and contained rhPDGF-BB and rhIGF-I, while region C exhibited a similar microstructure to the bone tissue and contained rhBMP-2. Primary rat skin fibroblasts, soft tissue fibroblasts, and osteoblasts were then cultured on regions A, B, and C of the CGS, respectively and their phenotypic characteristics were evaluated in this heterogenous environment. In the absence of growth factors, we found that the structural cues presented in every region played a key role in maintaining the region-specific cell functions and heterogeneity during a heterogeneous culture. In the presence of growth factors, we found that spatially localizing the growth factors at their respective regions resulted in enhanced region-specific cell functions and maintained region-specific cell heterogeneity compared to supplementation, which resulted in a significant reduction of cell growth and loss of phenotype. Our data suggest that providing biomimetic structural cues relevant to each cell phenotype and controlling the presentation of growth factors play a crucial role in ensuring heterogeneity maintenance of distinct cell populations during a heterogeneous culture. The presented CGS herein provides a reliable platform for investigating different cells responses to heterogeneous culture in a physiologically relevant microenvironment. In addition, the model provides a unique platform for evaluating the feasibility and efficacy of different approaches for simultaneously delivering multiple growth factors or molecules from a single construct to achieve enhanced cell response while maintaining cellular heterogeneity during a heterogenous culture.

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Regenerative Engineering: Approaches to Limb Regeneration and Other Grand Challenges

Cited by 47 publications

References 12 publications

Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering

Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering

Robust phenotypic maintenance of limb cells during heterogeneous culture in a physiologically relevant polymeric-based constructed graft system

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