A study conducted in the laboratory of the Faculty of Dentistry, Universitas Gadjah Mada, has revealed an important finding: a combination of gypsum and carbonate hydroxyapatite (CHA) has been shown to be safe for soft tissues. The research, led by dr. Dyah Listyarifah, M.Sc., D.Med.Sci., together with a team from the Biomedical Laboratory of FKG UGM and the Histology Laboratory of the Faculty of Medicine, UGM, addressed a fundamental question that has received relatively little attention: how does soft tissue respond to a synthetic bone substitute before the material is used in patients in clinical settings?
Why Soft Tissue Needs to Be Tested First
Bone damage caused by injury, infection, or disease can result in long-term disability. In cases of extensive damage, bone may not be able to heal on its own, requiring physicians to use replacement materials, known as bone substitutes.
Bone substitutes can be obtained from the patient's own body (autograft), another human donor (allograft), or an animal source (xenograft). However, all three approaches have drawbacks, including the risk of immune rejection, disease transmission, and trauma to the donor site. This is why synthetic materials such as gypsum and CHA are increasingly being investigated.
Gypsum can easily fill irregular bone defects and triggers only a minimal inflammatory response. Unfortunately, gypsum is absorbed by the body too quickly, before sufficient new bone has had time to form. CHA, on the other hand, has a strong ability to guide new bone growth and is absorbed more slowly. Combining the two materials is therefore logically expected to produce a more ideal bone substitute.
However, before this combination can be used in humans, one critical question must be answered: is the material safe for the soft tissues that may come into contact with it during implantation? Unlike bone, soft tissue is known to produce a much stronger inflammatory response to foreign materials.
Rats, Implants, and Twenty-One Days of Observation
To answer this question, the research team implanted small 6-mm-diameter discs made from two types of materials—pure gypsum and a gypsum-CHA combination—into the subcutaneous tissue beneath the skin on the backs of 25 male Wistar rats. The thin implants, measuring 0.8 mm in thickness, were placed in the right and left paravertebral areas and observed on days 0, 5, 7, 14, and 21 after implantation.
Thin tissue sections were stained with Hematoxylin and Eosin and examined under a microscope by two independent observers. Each specimen was evaluated using a standard histological scale for soft-tissue implants, including the thickness of the fibrous capsule formed around the implant, the quality of the capsule, and the quality of the interface between the implant and the surrounding tissue.
The results were surprisingly positive. Statistically, no significant differences were found between the two implant groups throughout the entire observation period.
“Gypsum and the gypsum-CHA combination had the same level of histocompatibility in soft tissue up to day 21 after implantation.” — dr. Dyah Listyarifah, M.Sc., D.Med.Sci., lead researcher
Normal and Controlled Inflammation
This does not mean that there was no tissue response at all. The body naturally reacts to foreign materials, and this is normal.
From day 0 to day 7, acute inflammatory cells such as polymorphonuclear leukocytes (white blood cells that act as the body's “first responders” to foreign materials) appeared around both implants. Their numbers were nearly identical between the gypsum and gypsum-CHA groups. By days 14 and 21, the response shifted toward a chronic phase, characterized by the appearance of macrophages, foreign-body giant cells, and lymphocytes.
Macrophages are the body's “clean-up” cells, responsible for engulfing residual materials and cellular debris. In the gypsum implants, the number of macrophages gradually decreased over time because the gypsum was absorbed more rapidly. Meanwhile, in the gypsum-CHA implants, macrophages remained active through day 21 because the more slowly degraded CHA particles continued to provide mild stimulation.
One interesting detail was that the fibrous capsule formed around the pure gypsum on day 7 was thicker than the capsule surrounding the gypsum-CHA implant. However, overall, this difference was not statistically significant. Both materials were also shown to be non-toxic, as surrounding tissue fibroblasts were able to attach to and grow into the pores of the implants without any gaps indicating rejection.
A Small Step Toward the Clinic
This study is not the end of the long process of validating bone substitute materials. The researchers themselves emphasized that further testing is still required, including cytotoxicity testing (safety at the cellular level), hemocompatibility testing (safety in relation to blood cells), and observation over longer implantation periods.
However, these findings establish an important foundation. The gypsum-CHA combination, which was previously known to promote bone healing, has now also been shown not to cause harmful reactions in the surrounding soft tissues. This is a minimum requirement that must be met before a medical material can undergo further testing in humans.
For dentistry and orthopedics, these findings open the door a little wider: there is hope that, one day, patients with jawbone or other bone defects may receive treatment that is safer, more affordable, and free from the rejection risks that often accompany conventional transplantation procedures.
Authors: Achmad Zam Zam Aghasy, DDS, M.Kes.; Hazra Alifia Muharam
Photo: Freepik