An acellular biologic scaffold does not regenerate appreciable de novo muscle tissue in rat models of volumetric muscle loss injury

Aurora, Amit; Roe, Janet L.; Corona, Benjamin T.; Walters, James

doi:10.1016/j.biomaterials.2015.07.040

Cited by 132 publications

(149 citation statements)

References 54 publications

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“…As discussed previously, DECM scaffolds are known to exhibit poor biomechanical properties. In a recent example, the porcine UBM scaffold (MatriStem TM , ACell , Inc.) was found to be completely resorbed without tissue remodeling in a rodent musculotendinous junction defect model, suggesting that the scaffold may not be suitable for certain injuries where long-term mechanical support is required [13]. Additionally, DECM scaffold implantation is often reported to result in scar tissue deposition without sitespecific regeneration of tissues.…”

Section: Clinical Challenges Associated With Decellularized Matricesmentioning

confidence: 99%

“…Although the use of SIS increased the rate of healing and reduced the incidence of ulcer recurrence, scarless healing and complete regeneration of skin was not observed [43]. In rodent models of traumatic volumetric muscle loss (VML) injuries, DECM scaffolds such as rodent muscle-derived ECM [8,44], commercially available SIS-ECM [45] and porcine UBM matrix (MatriStem TM , ACell , Inc.) [13,46], did not appreciably regenerate muscle fiber in vivo and remodeled into a fibrotic scar. In a clinical case study by Mase et al, a military service member with traumatic skeletal muscle injury was treated with a porcine SIS scaffold into the defect site that resulted in functional improvement at 16 weeks without significant muscle fiber regeneration [47].…”

Section: Clinical Challenges Associated With Decellularized Matricesmentioning

confidence: 99%

“…Overall, these studies suggest that ECM scaffolds are capable of improving skeletal muscle function with little to no de novo muscle fiber regeneration. In the absence of muscle regeneration, the improvements in muscle function are possibly due to a fibrotic scar mediated mechanical bridging effect that increased force transmission through the myofibers [13,48,49]. Since scar tissue lacks the contractile properties of native muscle tissue, it leaves the traumatized muscle susceptible to reinjury.…”

Section: Clinical Challenges Associated With Decellularized Matricesmentioning

confidence: 99%

“…DECM scaffolds improve cell growth, migration, differentiation and can positively influence tissue repair and remodeling [3][4][5][6][7]. DECM from a variety of tissues such as skeletal muscle [8][9][10], brain [11,12], urinary bladder [2,5,13], small intestinal submucosa [14][15][16], liver [4,[17][18][19], skin/adipose tissue [20][21][22], blood vessels [23][24][25], heart valves [26,27] and tendons [28] have been used for tissue engineering applications.…”

Section: Introductionmentioning

confidence: 99%

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Decellularized extracellular matrices for tissue engineering applications

Elmashhady¹,

Kraemer²,

Patel³

et al. 2017

Electrospinning

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Decellularization removes cellular antigens while preserving the ultrastructure and composition of extracellular matrix (ECM). Decellularized ECM (DECM) scaffolds have been widely used in various tissue engineering applications with varying levels of success. The mechanical, architectural and bioactive properties of a DECM scaffold depend largely on the method of decellularization and dictate its clinical efficacy. This article highlights the advantages and challenges associated with the clinical use of DECM scaffolds. Poor mechanical strength is a significant disadvantage of some DECM scaffolds in the repair of load-bearing tissues as well as critical-size defects, where long-term mechanical support is required for the regenerating tissue. Combining DECM scaffolds with synthetic biocompatible polymers could provide a useful strategy to circumvent the issues of poor mechanical stability. This article reviews studies that have combined DECM scaffolds from various tissues with synthetic polymers to create hybrid scaffolds using electrospinning. These hybrid scaffolds provide a mechanical backbone while retaining the bioactive properties of DECM, thus offering a significant advantage for tissue engineering and regenerative medicine applications.

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Section: Clinical Challenges Associated With Decellularized Matricesmentioning

confidence: 99%

Section: Clinical Challenges Associated With Decellularized Matricesmentioning

confidence: 99%

Section: Clinical Challenges Associated With Decellularized Matricesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Decellularized extracellular matrices for tissue engineering applications

Elmashhady¹,

Kraemer²,

Patel³

et al. 2017

Electrospinning

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“…In fact, current preclinical reports employ multiple cell types, as well as a variety of natural or synthetic scaffolds, with demonstrable success in terms of improved functional recovery of VML injuries [Conconi et al, 2005;De Coppi et al, 2005;Kroehne et al, 2008;Moon du et al, 2008;Ayele et al, 2010;Merritt et al, 2010a;Borselli et al, 2011;Machingal et al, 2011;Page et al, 2011;Rossi et al, 2011;Fuoco et al, Corona et al, 2013aCorona et al, , b, 2014Juhas et al, 2014;Pilia et al, 2014;Madden et al, 2015]. In contrast, more limited functional outcomes generally result from implantation of acellular scaffolds alone [De Coppi et al, 2006;Kin et al, 2007;Merritt et al, 2010b;Turner et al, 2010;Aurora et al, 2015]. The importance of including a cellular component for enhanced functional recovery of implantable therapeutics for skeletal muscle tissue repair and regeneration has been discussed in detail in recent publications and will not be further considered herein [Christ et al, 2015a, b].…”

Section: Cell-based Tissue Engineering Approaches To Skeletal Muscle mentioning

confidence: 99%

The Potential of Combination Therapeutics for More Complete Repair of Volumetric Muscle Loss Injuries: The Role of Exogenous Growth Factors and/or Progenitor Cells in Implantable Skeletal Muscle Tissue Engineering Technologies

Passipieri¹,

Christ²

2016

Cells Tissues Organs

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Despite the robust regenerative capacity of skeletal muscle, there are a variety of congenital and acquired conditions in which the volume of skeletal muscle loss results in major permanent functional and cosmetic deficits. These latter injuries are referred to as volumetric muscle loss (VML) injuries or VML-like conditions, and they are characterized by the simultaneous absence of multiple tissue components (i.e., nerves, vessels, muscles, satellite cells, and matrix). There are currently no effective treatment options. Regenerative medicine/tissue engineering technologies hold great potential for repair of these otherwise irrecoverable VML injuries. In this regard, three-dimensional scaffolds have been used to deliver sustained amounts of growth factors into a variety of injury models, to modulate host cell recruitment and extracellular matrix remodeling. However, this is a nascent field of research, and more complete functional improvements require more precise control of the spatiotemporal distribution of critical growth factors over a physiologically relevant range. This is especially true for VML injuries where incorporation of a cellular component into the scaffolds might provide not only a source of new tissue formation but also additional signals for host cell migration, recruitment, and survival. To this end, we review the major features of muscle repair and regeneration for largely recoverable injuries, and then discuss recent cell- and/or growth factor-based approaches to repair the more profound and irreversible VML and VML-like injuries. The underlying supposition is that more rationale incorporation of exogenous growth factors and/or cellular components will be required to optimize the regenerative capacity of implantable therapeutics for VML repair.

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