Internal fixation is required for reconstructive surgery on fractured bone to maintain the anatomic reduction in the fragments and provide stability during the healing process. In the past, bone fractures were fixed by the methods of applying metal implants. To substitute the metal implants for internal fracture fixation, numerous biodegradable materials (BMs) were developed. Biodegradable implants are increasingly used in regenerative medicine and sports medicine [1]. To be used successfully for fracture fixation, BMs must have sufficient strength and not degrade too rapidly. In an ideal scenario, these implants would break down as the wound healed, transferring load gradually to the healing tissue.

Today’s regenerative medicine and tissue engineering are using a large portfolio of BMs, which are used largely as substitutes for damaged or missing hard tissue. Natural and synthetic biodegradable polymers and hydrolysable metals make the main components for the creation of temporary medical implants [2]. Recently, much attention has been paid to materials based on extracellular matrix (ECM) ^[3][4][3,4], which consist of proteins, glycosaminoglycans and glycoproteins [5]. There is no doubt that the development and application research of BMs has significantly intensified in the last decade, as evidenced by the growing number of publications in this area.

2. Indications and Materials for Biodegradable Implants in Orthopedics

There are several typical clinical indications for the use of biodegradable implants in orthopedics, which are mostly used for fractures stabilization, osteotomy procedures, bone grafts and fusions ^[6][7][6,7]. Furthermore, they can be used in re-attachment of tendons, ligaments, meniscal cracks, and other tissue structures [8]. The most common indications for biodegradable implants in orthopedics include anterior cruciate ligament reconstruction, meniscus repair, and ankle fracture treatment [9]. The occurrence of clinical indications for biodegradable implants is comprehensively demonstrated in Figure 1. As demonstrated in Figure 1, there are several clinical indications on the upper limb. In the shoulder area, biodegradable implants are applied in fracture fixation of the glenoid fossa and in shoulder lesions repair [10]. Other shoulder indications include reconstruction of various intra-articular and extra-articular abnormalities. Clinical indications for the arm include osteochondral fractures of head and epicondyles of the humerus [11]. Biodegradable implants are also used for fracture fixation of the radial head and radial neck ^[12][13][14][12,13,14]. Furthermore, these implants are used to treat fractures of metacarpals and phalanges, fixation of tendons and collateral ligaments, lunate and scaphoid fractures ^[15][16][17][15,16,17]. Further clinical indications include those which are related to the lower limb. In the knee region, anterior cruciate ligament reconstructions are treated with the use of biodegradable implants [10]. Biodegradable pins are appropriate for osteochondral fractures. In addition, meniscal tacks and biodegradable suture anchors allow for new ways to perform reconstruction after complicated knee injuries. Patella fractures can also be treated with these implants. The foot and ankle region also benefits from these innovative implants. Here implants made from BM are used for treatment of isolated fractures of the internal malleolus ^[18][19][20][18,19,20]. Further indications include fractures of metatarsals and phalanges, flake fracture of the talus and calcaneus ^[21][22][23][21,22,23]. In addition, Lisfranc’s dislocation, syndesmotic disruptions and osteotomies for hallux valgus are among the health conditions that can be treated with biodegradable implants. Traditionally, non-degradable metals such as inert stainless steel, titanium and its alloys, and cobalt-chromium alloys were used for internal fixation of fractured bones and joints [24]. These materials used to lack bone ingrowth in the scaffold and cause that the scaffold did not respond to changes in bone topology [25]. However, this issue is solvable when scaffold surface has porous structure or coatings that promote bone cell attachment and growth. Biodegradable materials used in orthopedic applications include degradable synthetic polymers and degradable metals and alloys [2]. According to Hoffman [26] dozens of different polymeric BMs have been developed to substitute metal implants for internal fracture fixation, such as bone plates, screws, and intramedullary pins. He adds that their main limitation is the loss of mechanical strength within a short time interval. On the other hand, polymeric BMs have overcome metals in some important quality attributes, such as elasticity, flexibility, longevity, and bio-inertness [27]. Among them, polyglycolide (PGA), polylactide (PLA), and polycaprolactone (PCL) have been the most widely used for this purpose due to their good biocompatibility [28]. Polymers PLA, PGA and their co-polymer compositions are most often used in applications that include fracture-fixation pins and plates, interference screws, suture anchors and other fixation implants as they are highly resorbable [29]. Implants made from PLA are used, e.g., for the surgery and/or treatment of maxillofacial fractures, ankle fractures and syndesmosis injury ^[30][31][30,31]. The degradable polymer poly-l-d, l-lactide (PLDLA) is applicable for the treatment of mandibular fractures, since it has good mechanical properties. The screws made from this material provided the same fixation strength as titanium screws [32]. Another synthetic polymer Poly-l-lactic (PLLA) is notable for its gradual degradation and thanks to that is applicable in orthopedics for anterior cruciate ligament reconstruction, ankle fracture treatment or meniscus injury therapy ^[33][34][33,34]. Bio-absorbable screws made from copolymer PLLA/PGA are suitable, e.g., for fixation of osteochondritis dissecans lesions [35]. Biodegradable metals are seen as promising alternatives to non-biodegradable metals. Among the metals, magnesium (Mg), zinc (Zn), and iron (Fe) are considered as materials with the most biodegradable potential [36]. During the last decades, Mg-based alloys have been intensively explored by researchers in the context of orthopedic applications. The advantages of Mg-based biodegradable metals are that their bioactivity enhances osteogenesis and that their elastic modulus matches that of bone ^[37][38][37,38]. Magnesium’s good properties mean that it is often used to treat bone fractures, for example in the form of an implantable screw. Typically used magnesium alloys include high-purity magnesium alloy, MgCa0.8 alloy, MgYREZr alloy and Mg-Al-Zn alloys. For example, the MgYREZr screws were applied to treat hallux valgus with good therapeutic effect [39]. Currently, Zinc-based BMs are receiving considerable attention. A comprehensive review of related research progress on Zn-based BMs for orthopedic internal fixation is presented in a study by Liu et al. [40]. Its authors point out the important fact that there is a critical need for development of BMs for fixation of fractures at heavy load-bearing bone sites where fractures occur most frequently.

3. Smart Biodegradable Materials for Tissue Engineering

Traditionally, biodegradable materials were designed to interact with living tissue temporarily or permanently to provide functions, such as mechanical support. Smart BMs are defined as those that respond to external stimuli, such as light, magnetic fields, ultrasound, etc. Typical smart BMs include, e.g., photoresponsive and chemoresponsive polymers that combine sensing and actuation within the same material, without need for external devices ^[41][42][43][119,120,121]. Moreover, development of smart bioactive glasses for bone contact applications is becoming a hot research area in TE ^[44][122]. Recent research in this domain focuses on the molecular interaction of bioactive glass-based ionic dissolution products with their physiological surrounding environment ^[45][123]. Another example of smart biomaterial is decellularized extracellular matrix, which is the noncellular component of tissue that retains relevant biological cues for cells ^[46][124]. The related research is oriented towards directly using the component of the dECM to obtain scaffolds simulating native ECM ^[47][125]. Montoya et al. ^[48][126] suggested classifying smart biomaterials according to their degree of interaction with their external environment and the subsequent biological responses to clarify the concept of smartness in this context. The authors categorized smart materials into three kinds, namely, active, responsive, and autonomous. The inert biomaterial is just biocompatible or bioinert, while the active one can provide planned one-way interaction, e.g., bioactive therapy, with biological tissue. One of the first materials of this category was bioactive glass composed of four oxides, namely SiO₂-CaO-Na₂O-P₂O₅, introduced by Hench ^[49][127]. The main limitation of active biomaterials lies in the limited duration and efficacy of the therapy due to their degradation in a biological environment. Active biomaterials, namely polymer and lipid-based ones are often used for the controlled release of drugs like antibiotics, antiseptics, vitamins, and statins ^[50][51][128,129]. Responsive biomaterials can receive a stimulus and provide feedback to it through triggered reactions. Examples of such materials are artificial cells and hydrogels ^[52][130]. Especially, the need for biodegradable hydrogels in biomedical applications is significant since their physical properties can be designed to follow those of articular cartilage ^[53][131]. Recent developments in the design of responsive nanocomposite hydrogels increase their potential in biomedical applications including their utilization as therapeutic platforms for the delivery of precisely prescribed medications ^[54][132]. The responsive functionalities of biomaterials can be triggered from internal or external sources. The stimuli coming from inside an organism are internal, while external sources generate stimuli from outside of the body like heat, light, chemicals, or pressure. Both kinds of the signals can be categorized into three groups: biological, chemical, and physical ^[55][133]. For instance, PLLA-based biomaterials processed into piezoelectric structures can be engineered as scaffolds for promoting cellular growth during electrostimulation ^[56][134]. The low piezoelectric effect of PLLA is similar in magnitude to that of natural biomacromolecules like collagen ^[57][135] giving it the ability to interact with biological systems without being rejected ^[58][136]. The highest degree of smartness represents biomaterials capable of autonomously responding to the surrounding environment. Biomaterials with such properties can be considered as kind of dynamic biomaterials, which respond to stimuli by autonomous feedback loops ^[52][130]. The model of autonomous biomaterial is graphically illustrated in Figure 2. Smart biomaterials can be applied, e.g., for the regulation of stem cell activity, as well as to understand complex cellular processes ^[59][137]. The control of dynamic biomaterials after implantation in the body becomes challenging research in this field. For this purpose, Badeau et al. ^[60][138] employed a logic-based peptide hydrogel as a miniature computer system taking inputs from the surrounding microenvironment to decide when to release therapeutic agents for drug delivery. Research devoted to smart biomaterials in biomedical engineering is widely published, and its development is comprehensively summarized in recent works ^[61][62][63][139,140,141].