Age-related changes in wound healing

Kerkhof, P.C.M. van de; Bergen, Bert van; Spruijt, Karin I.; Kuiper, Jacob

doi:10.1111/j.1365-2230.1994.tb02684.x

Cited by 75 publications

(14 citation statements)

References 68 publications

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“…This might partially account for the poor healing observed in aging tendons. Similar results have been obtained in studies of wound healing, where the proliferative capacity of fibroblast progressively decreases over time [26,27]. …”

Section: Discussionsupporting

confidence: 85%

Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes

Pang

et al. 2013

BMC Musculoskelet Disord

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BackgroundMost tendon pathology is associated with degeneration, which is thought to involve cyclic loading and cumulative age-related changes in tissue architecture. However, the association between aging and degeneration of the extracellular matrix (ECM) in tendons has not been investigated extensively.MethodsWe examined tenocytes from Achilles tendons taken from rats of three different ages (2, 12, and 24 months). Tenocyte viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative real-time polymerase chain reaction (PCR) was used to determine the levels of mRNAs that encode type-I collagen, matrix metalloproteinase (MMP)-2 and −9, tissue inhibitor of metalloproteinase (TIMP)-1 and −2 and transforming growth factor (TGF)-β1. Gelatin zymography was used to evaluate the enzymatic activities of MMP-2 and −9. Furthermore, the concentration of TGF-β1 in conditioned medium was evaluated using enzyme-linked immunosorbent assay (ELISA).ResultsThe results of the MTT assay showed that the number of viable tenocytes decreased with age. No differences were observed in the levels of mRNAs that encode type-I collagen and TGF-β1 among the three age groups, and the TGF-β1 concentration did not change with age. However, mRNAs that encode MMP-2 and −9 were significantly more abundant in tenocytes from the aging group, and gelatin zymography revealed that the enzymatic activities of MMP-2 and −9 also increased significantly with age. Furthermore, as compared with young group, mRNAs that encode TIMP-1 and −2 were significantly decreased in tenocytes from the aging group.ConclusionsActivities of MMP-2 and MMP-9 in tenocytes increase with age. This might provide a mechanistic explanation of how aging contributes to tendinopathy or tendon rupture with age.

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Section: Discussionsupporting

confidence: 85%

Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes

Pang

et al. 2013

BMC Musculoskelet Disord

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“…Animal models of chronic wounds are just delayed-healing models, with marked differences in pathophysiology [53–55]. Wounds of size surpassing 5 cm 2 in humans and lasting for a duration exceeding six months [56, 57] and age-related changes and chronic disorders common in chronic wound patients are next to impossible to be studied in animals [58]. Elderly patients with chronic wounds are more likely to respond to allogeneic therapy owing to the immune dysregulation in such patients [59].…”

Section: Discussionmentioning

confidence: 99%

Enhanced Healing of Diabetic Wounds by Subcutaneous Administration of Human Umbilical Cord Derived Stem Cells and Their Conditioned Media

Shrestha

Zhao

Chen

et al. 2013

International Journal of Endocrinology

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Objective. Mesenchymal stem cells (MSCs) isolated from the umbilical cord and their conditioned media (CM) can be easily obtained and refined compared with stem cells from other sources. Here, we explore the possibility of the benefits of these cells in healing diabetic wounds. Methodology and Results. Delayed wound healing animal models were established by making a standard wound on the dorsum of eighteen db/db mice, which were divided into three groups with six mice in each: groups I, II, and III received PBS, UC-MSC, and CM, respectively. UC-MSC and their CM significantly accelerated wound closure compared to PBS-treated wounds, and it was most rapid in CM-injected wounds. In day-14 wounds, significant difference in capillary densities among the three groups was noted (n = 6; P < 0.05), and higher levels of VEGF, PDGF, and KGF expression in the CM- and UC-MSC-injected wounds compared to the PBS-treated wounds were seen. The expression levels of PDGF-β and KGF were higher in CM-treated wounds than those in UC-MSC-treated wounds. Conclusion. Both the transplantation of UC-MSC and their CM are beneficial to diabetic wound healing, and CM has been shown to be therapeutically better than UC-MSC, at least in the context of diabetic wound healing.

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“…Associated with each of these three risk factors is a host of local and systemic effects that alter blood flow and decrease both the speed and quality of wound healing [25-27]. Small vessel disease associated with these risk factors may decrease mastectomy flap perfusion.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Interactions with a High Intraoperative Expander Fill Volume Increase the Risk for Mastectomy Flap Necrosis

et al. 2013

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PurposeProsthetic-based breast reconstruction is performed with increasing frequency in the United States. Major mastectomy skin flap necrosis is a significant complication with outcomes ranging from poor aesthetic appearance to reconstructive failure. The present study aimed to explore the interactions between intraoperative fill and other risk factors on the incidence of flap necrosis in patients undergoing mastectomy with immediate expander/implant-based reconstruction.MethodsA retrospective review of 966 consecutive patients (1,409 breasts) who underwent skin or nipple sparing mastectomy with immediate tissue expander reconstruction at a single institution was conducted. Age, body mass index, hypertension, smoking status, premastectomy and postmastectomy radiation, acellular dermal matrix use, and application of the tumescent mastectomy technique were analyzed as potential predictors of flap necrosis both independently and as synergistic variables with high intraoperative fill. The following three measures of interaction were calculated: relative excess risk due to interaction, attributable proportion of risk due to interaction, and synergy index (SI).ResultsIntraoperative tissue expander fill volume was high (≥66.7% of the maximum volume) in 40.9% (576 of 1,409 breasts) of cases. The unadjusted flap necrosis rate was greater in the high intraoperative fill cohort than in the low fill cohort (10.4% vs. 7.1%, p=0.027). Multivariate logistic regression did not identify high intraoperative fill volume as an independent risk factor for flap necrosis (odds ratio 1.442, 95% confidence interval 0.973-2.137, p=0.068). However, four risk factors were identified that interacted significantly with intraoperative fill volume, namely tumescence, age, hypertension, and obesity. The SI, or the departure from additive risks, was largest for tumescence (SI, 25.3), followed by hypertension (SI, 2.39), obesity (SI, 2.28), and age older than 50 years (SI, 1.17).ConclusionIn the postmastectomy, hypovascular milieu, multiple risk factors decreasing flap perfusion interact with high intraoperative fill volume to cross a threshold and synergistically increase the risk of flap necrosis.

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Age-related changes in wound healing

Cited by 75 publications

References 68 publications

Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes

Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes

Enhanced Healing of Diabetic Wounds by Subcutaneous Administration of Human Umbilical Cord Derived Stem Cells and Their Conditioned Media

Synergistic Interactions with a High Intraoperative Expander Fill Volume Increase the Risk for Mastectomy Flap Necrosis

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