Bone fillers are used in a wide array of dental and orthopedic applications to facilitate bone repair and regeneration. It has been reported that the current bone filler market size exceeds an estimated $493 million and is expected to reach $931 million by 2025 [[1], [2], [3], [4], [5], [6]]. In the clinical domain of dental restoration, bone fillers play a significant role. Current best practice procedures require these bone graft materials for tooth site preparation in the maxilla and mandible before securing dental implants. Placing implants in areas with poor bone quality increases the risk of implant failure or rejection, and addressing bony defects in the jaw, such as socket preservation and ridge augmentation, is imperative for effective site preparation and subsequent successful dental implantation [7,8]. Meticulous planning and site preparation are essential as primary dental implant failure can severely compromise the stomatognathic system and reduce subsequent dental restorative options [9,10]. Thorough site development with bone grafting is a key strategy to enhance the probability of successful outcomes [2].

Additionally, dental bone fillers play a crucial role in bimaxillary ridge augmentations. Such procedures are complicated by the microbiologically diverse oral environment. The use of sterile instruments is insufficient to prevent site contamination during the procedure, creating a significant risk for potentially pathogenic bacteria to infect these “immune privileged” bone fillers that are “foreign body” materials. This leads to suboptimal clinical outcomes or outright failures, necessitating further and repeated treatments [11,12]. Resolving this issue is a current clinical need, requiring solutions [13].

Today, many types of bone fillers are used in dentistry, including, but not limited to, autografts, calcium phosphate ceramics, demineralized bone matrix (DBM), allografts, and decellularized xenografts such as pericardium, reconstituted collagen, and porcine- or bovine-derived bone grafts [4]. Despite their routine use, reports indicate that 40–60 % of the alveolar ridge is resorbed within the initial 2–3 years post-extraction [3,5], leaving areas devoid of viable bone tissue required for subsequent restorative dental work. It is worth pointing out that infection is a significant contributor to this bone resorption, making grafting in this area difficult and even more prone to infection, however currently available bone fillers lack antimicrobial properties [6]. This encourages the development of antimicrobial or bacteriostatic fillers and scaffoldings, hence the rationale for this study.

Although autograft is considered the gold standard for bone regeneration, its use as a filler for dental implantation is limited due to the invasiveness and pain associated with procuring donor grafts [[13], [14], [15]]. Additionally, autograft harvest requires considerably more sterile operative procedures than what is available in typical dental clinics, which is an additional constraint, and the procurement can be costly, making it less accessible for dentists. Considering the limitations associated with autograft bone, allograft materials such as DBM are frequently employed [16]. However, their utilization is similarily hampered by a constrained supply and escalating demand. Therefore, developing an effective synthetic material that can replace these autograft fillers is now an unmet market need. If they match autograft's bone regeneration capacity and outperform DBM, then these engineered scaffolds would hold significant promise as the alternative to autografts.

Our previous investigations have revealed that fluoridated apatite-based bone graft serves as an optimal engineered bone scaffold in both in vitro and in vivo studies [17,18]. Despite this positive effect, scaffolds lack antimicrobial properties. The existing apatite literature supports the paradigm that the antimicrobial properties of the fluorapatite (FA) scaffold can be improved by substituting a percentage of the calcium ions with various biocidal bivalent metal ions that are known to have antibiotic properties [[19], [20], [21]]. Zinc (Zn) is among these metals, with Zn-substituted hydroxyapatite (HA) found in both the bone and enamel of human teeth [22]. While Zn plays a critical role in numerous important biological functions, its compounds are known to have antimicrobial properties [[22], [23], [24], [25], [26], [27]]. A study demonstrated that 1.6% Zn substitution in HA imparts an antimicrobial effect [25]. The antibacterial and antifungal behavior of Zn-doped HA has been demonstrated in a nano-rod configuration, allowing a high release of zinc ions and improving performance against oral cavity bacteria [28]. Additionally, some literature suggests that Zn substitution may positively influence bone formation and mineralization due to its reported stimulatory effect on eukaryotic cells [29,30]. Currently, little information is available about the potentially salubrious effect of Zn-doped fluorapatite (Zn-doped FA).

This study is designed to bridge this gap and investigate the efficacy of Zn-doped FA as an antimicrobial scaffold through comprehensive in vitro and in vivo analyses. The in vitro studies included planktonic and biofilm gram-positive and gram-negative bacteria and stem cell culture assays. The in vivo experiments utilized a rat mandible injury model.