Repair of large complex ventral wall hernias is challenging and outcomes are often poor due to hernia recurrence and compromised abdominal wall function. Currently, biological grafts are used to assist in repairing these complex hernias. Dermis grafts are often chosen because of their mechanical characteristics; however, dermis does not have the ability to promote the muscle regeneration needed to regain abdominal wall function. In contrast, small intestinal submucosa (SIS) grafts have been shown to promote muscle generation in volumetric muscle loss (VML) models. Hence, the objective of this study is to investigate the extent to which SIS grafts can be used together with dermis grafts to repair and promote muscle regeneration in a full-thickness abdominal wall defect in a rat model. The dermis layer is intended to mechanically bridge the defect and support constructive tissue remodeling while the SIS is intended to degrade and promote neo-muscle formation. After 16 weeks of implantation, we found only a small amount of vascularized muscle (<10% of the defect area) in the repaired defects. No significant difference in defect muscle area was found between the groups receiving the dermis + SIS scaffolds and the control (dermis alone) group. Our findings indicate that the SIS constructions investigated could not promote appreciable muscle regeneration in this rigorous animal model of VML and incomplete abdominal closure. Future investigation into combination scaffold, cell and molecular therapies would be warranted to address the need for functional muscle regeneration in challenging clinical conditions such as complex abdominal wall repair.
* Identifying biomarkers of disease severity and prognostic factors for healing after rotator cuff repair would allow improved clinical decision-making about the treatment of patients with rotator cuff pathologies and possibly identify targets for therapeutic intervention to promote healing.* The state of investigations to identify biomarkers of disease severity or repair success has been neither systematic nor standardized. Clinical studies to date have been largely exploratory, with small sample sizes and univariate analyses.* Current evidence shows that inflammatory biomarkers (interleukin 1 [IL-1β], interleukin 1 receptor antagonist [IL-1ra], tumor necrosis factor alpha [TNF-α], cyclooxygenase-2 [COX-2], inducible nitric oxide synthase [iNOS]) and matrix remodeling biomarkers (biglycan, aggrecan, and members of the collagen and matrix metalloproteinase [MMP] families) were found to be significantly associated with rotator cuff disease severity. Similarly, inflammatory biomarker COX-2 and matrix remodeling biomarkers (biglycan, tissue inhibitor of metalloproteinase [TIMP]-1, and members of the collagen and MMP families) were found to be significantly associated with rotator cuff retears.* Future studies investigating biomarkers of rotator cuff disease severity and healing should be standardized and should employ sample sizes large enough to allow for adequate power and multivariate analyses. Genetic and cellular biomarkers should be investigated, in addition to the more typical biochemical and structural factors. Progress would be greatly facilitated by forming a consortium of experts to define a strategic approach to biomarker research in rotator cuff disease and repair.
Wounds causing extensive injury loss of muscle, also known as volumetric muscle loss (VML), are frequently associated with high-energy civilian trauma and combat-related extremity injuries. Currently, no effective clinical therapy is available for promoting de novo muscle tissue regeneration to restore muscle function following VML. Recent studies have shown evidence that osteoactivin (OA), a transmembrane glycoprotein, has the ability to prevent skeletal muscle atrophy in response to denervation. Therefore the objective of this study is to investigate the potential regenerative effect of OA embedded and delivered via a cross-linked gelatin hydrogel within a volumetric tibialis anterior muscle defect in a rat model. After 4 weeks, however, no evidence for muscle formation was found in defects treated with either low (5 μg/ml) or high (50 μg/ml) OA. It is possible that a different delivery scaffold, delivery kinetics, or OA concentration may have yielded an alternate outcome, or it is also possible that the spaciostructural environment of VML, or the local (versus systemic) delivery of OA, simply does not support any potential regenerative activity of OA in VML. Together with prior work, this study demonstrates that an efficacious and scalable therapy for regenerating muscle volume and function in VML remains a veritable clinical challenge worthy of continued future research efforts.
Biologic grafts used in hernia repair undergo rapid cellular infiltration and remodeling, but their premature degradation often results in hernia recurrence. We hypothesize that a temporary barrier that prevents infiltration of acute inflammatory cells into the graft during the initial 4 weeks of implantation could mitigate graft degradation. The purpose of this study is to design tyramine‐substituted hyaluronan (THA) hydrogel coatings with tunable degradation properties, as a means to develop a resorbable barrier for human acellular dermis grafts (HADM). THA plugs prepared at different cross‐linking densities, by varying cross‐linking agent concentration (0.0001–0.0075% H2O2), demonstrated varying rates of in vitro degradation (25 U/mL hyaluronidase, 48 h). Based on these results, HADM grafts were coated with THA at three cross‐linking densities (0.0001%, 0.00075%, and 0.003% H2O2) and THA coating degradation was evaluated in vitro (25 U/mL hyaluronidase, 48 h) and in vivo (rat intraperitoneal implantation, 1–4 weeks). THA coatings degraded in vitro and in vivo with the lowest cross‐linking density (0.0001% H2O2), generally showing greater degradation as evidenced by significant decrease in coating cross‐sectional area. However, all three coatings remained partially degraded after 4 weeks of in vivo implantation. Alternate strategies to accelerate in vivo degradation of THA coatings are required to allow investigation of the study hypothesis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2664–2672, 2019.
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