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Related Concept Videos

Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
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The Functions of the Skeletal System01:22

The Functions of the Skeletal System

The most apparent functions of the skeletal system are support, protection, and movement. However, bone tissue also performs several other critical metabolic functions. For one, the bone matrix acts as a reservoir for a number of minerals important to the functioning of the body, especially calcium and phosphorus. These minerals, present in the bone tissue, can be released back into the bloodstream when required. Calcium ions, for example, are essential for muscle contractions and controlling...
Bone Remodeling and Repair01:31

Bone Remodeling and Repair

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...

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Modulating iMSC Spheroid Function with Mechanically Tunable Hydrogels to Strengthen the Bone-Muscle Axis.

Thi Thai Thanh Hoang1, Andrea C Filler1, David H Ramos-Rodriguez1

  • 1Department of Orthopaedic Surgery, UC Davis Health, Sacramento, California 95817, United States.

ACS Biomaterials Science & Engineering
|December 15, 2025
PubMed
Summary

This study presents a tunable hydrogel system for simultaneous muscle and bone repair using stem cell spheroids. Stiffness guides cell behavior, enabling targeted tissue regeneration for improved musculoskeletal healing.

Keywords:
bonegelatin hydrogelsmesenchymal stem cellsmusclespheroids

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Stem Cell Biology

Background:

  • Bone fractures frequently cause combined bone and muscle damage, necessitating advanced regenerative therapies.
  • Current treatments often address bone and muscle injuries separately, highlighting a need for integrated approaches.

Purpose of the Study:

  • To develop a gelatin-based hydrogel system with adjustable stiffness for guiding induced pluripotent stem cell (iPSC)-derived mesenchymal stromal cell (iMSC) spheroids.
  • To investigate the role of hydrogel stiffness and reciprocal cell signaling in promoting simultaneous bone and muscle regeneration.

Main Methods:

  • Fabrication of gelatin hydrogels using hydrogen peroxide and horseradish peroxidase, with tunable stiffness (1.6–9.3 kPa).
  • Encapsulation of iMSC spheroids within hydrogels to facilitate localized secretome release.
  • Culture of iMSC spheroids in varying stiffness hydrogels and in response to C2C12 myoblast secretome.

Main Results:

  • Soft hydrogels (1.6 kPa) with iMSC spheroids promoted myogenic differentiation of C2C12 myoblasts through paracrine signaling.
  • Stiffer hydrogels (9.3 kPa) enhanced osteogenic differentiation of iMSCs when exposed to the myoblast secretome.
  • Demonstrated synergistic effects of stiffness and secretome signaling on iMSC differentiation.

Conclusions:

  • Tunable hydrogels can direct iMSC behavior for distinct tissue regeneration outcomes.
  • This platform offers a promising "two-in-one" strategy for combined musculoskeletal tissue repair.
  • Highlights the potential of biomaterial stiffness and cell-cell communication in regenerative medicine.