Early pH Changes in Musculoskeletal Tissues upon Injury—Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

Abstract

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release.

Prevent or Cure—The Unprecedented Need for Self‐Reporting Materials

“…[ 90 , 91 , 92 , 93 ] Especially in the fields of drug delivery, bio‐ or nanotechnology, pH‐responsive materials are of high interest since certain pH values are characteristic for either healthy (pH≈7.4) or diseased tissue (pH<7). [ 94 , 95 , 96 ] Therefore, particles with different fluorescent characteristics in their swollen or shrunken state facilitate the reporting of environmental changes depending on the pH values.…”

Vorbeugen oder Heilen – die beispiellose Notwendigkeit von selbstberichtenden Materialien

“…Die Änderung der Partikelgröße und Beschaffenheit muss jedoch nicht allein thermisch induziert werden, sondern kann auch durch pH‐Änderungen verursacht werden [90–93] . Besonders in den Bereichen des Medikamententransports, der Bio‐ oder Nanotechnologie sind pH‐responsive Materialien von großem Interesse, da bestimmte pH‐Werte entweder für gesundes (pH≈7.4) oder für krankes Gewebe (pH<7) charakteristisch sind [94–96] . Daher ermöglichen Partikel mit unterschiedlichen Fluoreszenzeigenschaften in ihrem geschwollenen oder geschrumpften Zustand die Berichterstattung von pH‐Wert‐abhängigen Umgebungsänderungen.…”

Biomaterials Regulating Bone Hematoma for Osteogenesis

“…The difference of growth factors and cytokines between fracture hematoma and muscle hematoma leads to either muscle regeneration or bone formation. [14] However, for large and segmental bone defects (SBDs), the bone regeneration requirement exceeds the natural potential for self-healing. Many studies have sought to unveil the causes of bone nonunions.…”

“…The difference of growth factors and cytokines between fracture hematoma and muscle hematoma leads to either muscle regeneration or bone formation. [ 14 ]…”