Incorporation of calcium phosphate cement into decellularized extracellular matrix enhances its bone regenerative properties

Colloids Surf B Biointerfaces. 2024 Dec:244:114175. doi: 10.1016/j.colsurfb.2024.114175. Epub 2024 Aug 25.

Abstract

Decellularized extracellular matrix (dECM) hydrogels are engineered constructs that are widely-used in the field of regenerative medicine. However, the development of ECM-based hydrogels for bone tissue engineering requires enhancement in its osteogenic properties. For this purpose, we initially employed bone-derived dECM hydrogel (dECM-Hy) in combination with calcium phosphate cement (CPC) paste to improve the biological and structural properties of the dECM hydrogel. A decellularization protocol for bovine bone was developed to prepare dECM-Hy, and the mechanically-tuned dECM/CPC-Hy was built based on both rheological and mechanical characteristics. The dECM/CPC-Hy displayed a double swelling ratio and compressive strength. An interconnected structure with distinct hydroxyapatite crystals was evident in dECM/CPC-Hy. The expression levels of Alp, Runx2 and Ocn genes were upregulated in dECM/CPC-Hy compared to the dECM-Hy. A 14-day follow-up of the rats receiving subcutaneous implanted dECM-Hy, dECM/CPC-Hy and mesenchymal stem cells (MSCs)-embedded (dECM/CPC/MSCs-Hy) showed no toxicity, inflammatory factor expression or pathological changes. Radiography and computed tomography (CT) of the calvarial defects revealed new bone formation and elevated number of osteoblasts-osteocytes and osteons in dECM/CPC-Hy and dECM/CPC/MSCs-Hy compared to the control groups. These findings indicate that the dECM/CPC-Hy has substantial potential for bone tissue engineering.

Keywords: Bone; Calcium phosphate cement; Decellularization; Hydrogel; Tissue engineering.

MeSH terms

  • Animals
  • Bone Cements* / chemistry
  • Bone Cements* / pharmacology
  • Bone Regeneration* / drug effects
  • Calcium Phosphates* / chemistry
  • Cattle
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Decellularized Extracellular Matrix / chemistry
  • Decellularized Extracellular Matrix / pharmacology
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism
  • Hydrogels / chemistry
  • Hydrogels / pharmacology
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Osteogenesis / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Engineering

Substances

  • Calcium Phosphates
  • calcium phosphate
  • Bone Cements
  • Decellularized Extracellular Matrix
  • Hydrogels
  • Core Binding Factor Alpha 1 Subunit